Edward E Smith

University of Pennsylvania, Philadelphia, PA, United States

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Publications (76)309.95 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: Schizophrenia is characterized by an abnormal dopamine system, and dopamine blockade is the primary mechanism of antipsychotic treatment. Consistent with the known role of dopamine in reward processing, prior research has demonstrated that patients with schizophrenia exhibit impairments in reward-based learning. However, it remains unknown how treatment with antipsychotic medication impacts the behavioral and neural signatures of reinforcement learning in schizophrenia. The goal of this study was to examine whether antipsychotic medication modulates behavioral and neural responses to prediction error coding during reinforcement learning. Patients with schizophrenia completed a reinforcement learning task while undergoing functional magnetic resonance imaging. The task consisted of two separate conditions in which participants accumulated monetary gain or avoided monetary loss. Behavioral results indicated that antipsychotic medication dose was associated with altered behavioral approaches to learning, such that patients taking higher doses of medication showed increased sensitivity to negative reinforcement. Higher doses of antipsychotic medication were also associated with higher learning rates (LRs), suggesting that medication enhanced sensitivity to trial-by-trial feedback. Neuroimaging data demonstrated that antipsychotic dose was related to differences in neural signatures of feedback prediction error during the loss condition. Specifically, patients taking higher doses of medication showed attenuated prediction error responses in the striatum and the medial prefrontal cortex. These findings indicate that antipsychotic medication treatment may influence motivational processes in patients with schizophrenia.
    Cognitive Affective & Behavioral Neuroscience 02/2014; · 3.87 Impact Factor
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    ABSTRACT: We hypothesized that semantic memory for object concepts involves both representations of visual feature knowledge in modality-specific association cortex and heteromodal regions that are important for integrating and organizing this semantic knowledge so that it can be used in a flexible, contextually appropriate manner. We examined this hypothesis in an fMRI study of mild Alzheimer's disease (AD). Participants were presented with pairs of printed words and asked whether the words matched on a given visual-perceptual feature (e.g., guitar, violin: SHAPE). The stimuli probed natural kinds and manufactured objects, and the judgments involved shape or color. We found activation of bilateral ventral temporal cortex and left dorsolateral prefrontal cortex during semantic judgments, with AD patients showing less activation of these regions than healthy seniors. Moreover, AD patients showed less ventral temporal activation than did healthy seniors for manufactured objects, but not for natural kinds. We also used diffusion-weighted MRI of white matter to examine fractional anisotropy (FA). Patients with AD showed significantly reduced FA in the superior longitudinal fasciculus and inferior frontal-occipital fasciculus, which carry projections linking temporal and frontal regions of this semantic network. Our results are consistent with the hypothesis that semantic memory is supported in part by a large-scale neural network involving modality-specific association cortex, heteromodal association cortex, and projections between these regions. The semantic deficit in AD thus arises from gray matter disease that affects the representation of feature knowledge and processing its content, as well as white matter disease that interrupts the integrated functioning of this large-scale network.
    Cognitive Affective & Behavioral Neuroscience 01/2014; · 3.87 Impact Factor
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    ABSTRACT: The concept of capacity has become increasingly important in discussions of working memory (WM), in so far as most models of WM conceptualize it as a limited-capacity mechanism for maintaining information in an active state, and as capacity estimates from at least one type of WM task-complex span-are valid predictors of real-world cognitive performance. However, the term capacity is also often used in the context of a distinct set of WM tasks, change detection, and may or may not refer to the same cognitive capability. We here develop maximum-likelihood models of capacity from each of these tasks-as well as from a third WM task that places heavy demands on cognitive control, the self-ordered WM task (SOT)-and show that the capacity estimates from change detection and complex span tasks are not correlated with each other, although capacity estimates from change detection tasks do correlate with those from the SOT. Furthermore, exploratory factor analysis confirmed that performance on the SOT and change detection load on the same factor, with performance on our complex span task loading on its own factor. These findings suggest that at least two distinct cognitive capabilities underlie the concept of WM capacity as it applies to each of these three tasks.
    Cognitive Affective & Behavioral Neuroscience 01/2014; · 3.87 Impact Factor
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    ABSTRACT: A major difference between humans and other animals is our capacity to maintain information in working memory (WM) while performing secondary tasks, which enables sustained, complex cognition. A common assumption is that the lateral prefrontal cortex (PFC) is critical for WM performance in the presence of distracters, but direct evidence is scarce. We assessed the relationship between fMRI activity and WM performance within subjects, with performance matched across distracter and no-distracter conditions. Activity in the ventrolateral PFC during WM encoding and maintenance positively predicted performance in both conditions, whereas activity in the presupplementary motor area (pre-SMA) predicted performance only under distraction. Other parts of the dorsolateral and ventrolateral PFCs predicted performance only in the no-distracter condition. These findings challenge a lateral-PFC-centered view of distracter resistance, and suggest that the lateral PFC supports a type of WM representation that is efficient for dealing with task-irrelevant input but is, nonetheless, easily disrupted by dual-task demands.
    Cognitive Affective & Behavioral Neuroscience 12/2013; · 3.87 Impact Factor
  • Schizophrenia Research 12/2013; · 4.59 Impact Factor
  • Teal S Eich, Edward E Smith
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    ABSTRACT: Orienting toward emotionally salient information can be adaptive, as when danger needs to be avoided. Consistent with this idea, research has shown that emotionally valenced information draws attention more so than does neutral information in healthy individuals. However, at times this tendency is not adaptive, and it may distract the individual from goals. People with schizophrenia (PSZ), though they frequently show deficits in attentional control, have also been shown to exhibit diminished recognition of and attention to emotional information. In the present study, we investigated how the presentation of emotionally salient information affected performance on a working memory task for PSZ and healthy controls (HC). We found that although hit rates were equal to those of HCs for PSZ, the PSZ made fewer false alarms-resulting in overall better performance-than did the HCs. Deficits in emotional processing in PSZ appear to provide an advantage to them in situations in which salient emotional information competes with active cognitive goals.
    Cognitive Affective & Behavioral Neuroscience 10/2013; · 3.87 Impact Factor
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    ABSTRACT: One of the most common deficits in patients with schizophrenia (SZ) is in working memory (WM), which has wide-reaching impacts across cognition. However, previous approaches to studying WM in SZ have used tasks that require multiple cognitive-control processes, making it difficult to determine which specific cognitive and neural processes underlie the WM impairment. We used functional magnetic resonance imaging to investigate component processes of WM in SZ. Eighteen healthy controls (HCs) and 18 patients with SZ performed an item-recognition task that permitted separate neural assessments of 1) WM maintenance, 2) inhibition, and 3) interference control in response to recognition probes. Before inhibitory demands, posterior ventrolateral prefrontal cortex (VLPFC), an area involved in WM maintenance, was activated to a similar degree in both HCs and patients, indicating preserved maintenance operations in SZ. When cued to inhibit items from WM, HCs showed reduced activation in posterior VLPFC, commensurate with appropriately inhibiting items from WM. However, these inhibition-related reductions were absent in patients. When later probed with items that should have been inhibited, patients showed reduced behavioral performance and increased activation in mid-VLPFC, an area implicated in interference control. A mediation analysis indicated that impaired inhibition led to increased reliance on interference control and reduced behavioral performance. In SZ, impaired control over memory, manifested through proactive inhibitory deficits, leads to increased reliance on reactive interference-control processes. The strain on interference-control processes results in reduced behavioral performance. Thus, inhibitory deficits in SZ may underlie widespread impairments in WM and cognition.
    Biological psychiatry 10/2013; · 8.93 Impact Factor
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    ABSTRACT: Our ability to form abstract representations of objects in semantic memory is crucial to language and thought. The utility of this information relies both on the representations of sensory-motor feature knowledge stored in long-term memory and the executive processes required to retrieve, manipulate, and evaluate this semantic knowledge in a task-relevant manner. These complementary components of semantic memory can be differentially impacted by aging. We investigated semantic processing in normal aging using functional magnetic resonance imaging (fMRI). Young and older adults were asked to judge whether two printed object names match on a particular feature (for example, whether a tomato and strawberry have the same color). The task thus required both retrieval of relevant visual feature knowledge of object concepts and evaluating this information. Objects were drawn from either natural kinds or manufactured objects, and were queried on either color or shape in a factorial design. Behaviorally, all subjects performed well, but older adults could be divided into those whose performance matched that of young adults (better performers) and those whose performance was worse (poorer performers). All subjects activated several cortical regions while performing this task, including bilateral inferior and lateral temporal cortex and left frontal and prefrontal cortex. Better performing older adults showed increased overall activity in bilateral premotor cortex and left lateral occipital cortex compared to young adults, and increased activity in these brain regions relative to poorer performing older adults who also showed gray matter atrophy in premotor cortex. These findings highlight the contribution of domain-general executive processing brain regions to semantic memory, and illustrate differences in how these regions are recruited in healthy older adults.
    Frontiers in Aging Neuroscience 01/2013; 5:46. · 5.20 Impact Factor
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    ABSTRACT: Patients with Alzheimer's disease have category-specific semantic memory difficulty for natural relative to manufactured objects. We assessed the basis for this deficit by asking healthy adults and patients to judge whether pairs of words share a feature (e.g. "banana:lemon - COLOR"). In an fMRI study, healthy adults showed gray matter (GM) activation of temporal-occipital cortex (TOC) where visual-perceptual features may be represented, and prefrontal cortex (PFC) which may contribute to feature selection. Tractography revealed dorsal and ventral stream white matter (WM) projections between PFC and TOC. Patients had greater difficulty with natural than manufactured objects. This was associated with greater overlap between diseased GM areas correlated with natural kinds in patients and fMRI activation in healthy adults for natural than manufactured artifacts, and the dorsal WM projection between PFC and TOC in patients correlated only with judgments of natural kinds. Patients thus remained dependent on the same neural network as controls during judgments of natural kinds, despite disease in these areas. For manufactured objects, patients' judgments showed limited correlations with PFC and TOC GM areas activated by controls, and did not correlate with the PFC-TOC dorsal WM tract. Regions outside of the PFC-TOC network thus may help support patients' judgments of manufactured objects. We conclude that a large-scale neural network for semantic memory implicates both feature knowledge representations in modality-specific association cortex and heteromodal regions important for accessing this knowledge, and that patients' relative deficit for natural kinds is due in part to their dependence on this network despite disease in these areas.
    NeuroImage 12/2012; · 6.25 Impact Factor
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    ABSTRACT: Many neuroimaging studies of semantic memory have argued that knowledge of an object's perceptual properties are represented in a modality-specific manner. These studies often base their argument on finding activation in the left-hemisphere fusiform gyrus-a region assumed to be involved in perceptual processing-when the participant is verifying verbal statements about objects and properties. In this paper, we report an extension of one of these influential papers-Kan, Barsalou, Solomon, Minor, and Thompson-Schill ( 2003 )-and present evidence for an amodal component in the representation and processing of perceptual knowledge. Participants were required to verify object-property statements (e.g., "cat-whiskers?"; "bear-wings?") while they were being scanned by functional magnetic resonance imaging (fMRI). We replicated Kan et al.'s activation in the left fusiform gyrus, but also found activation in regions of left inferior frontal gyrus (IFG) and middle-temporal gyrus, areas known to reflect amodal processes or representations. Further, only activations in the left IFG, an amodal area, were correlated with measures of behavioural performance.
    Cognitive Neuropsychology 09/2012; 29(3):237-48. · 1.52 Impact Factor
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    ABSTRACT: The prevailing view is that recreational methamphetamine use causes a broad range of severe cognitive deficits, despite the fact that concerns have been raised about interpretations drawn from the published literature. This article addresses an important gap in our knowledge by providing a critical review of findings from recent research investigating the impact of recreational methamphetamine use on human cognition. Included in the discussion are findings from studies that have assessed the acute and long-term effects of methamphetamine on several domains of cognition, including visuospatial perception, attention, inhibition, working memory, long-term memory, and learning. In addition, relevant neuroimaging data are reviewed in an effort to better understand neural mechanisms underlying methamphetamine-related effects on cognitive functioning. In general, the data on acute effects show that methamphetamine improves cognitive performance in selected domains, that is, visuospatial perception, attention, and inhibition. Regarding long-term effects on cognitive performance and brain-imaging measures, statistically significant differences between methamphetamine users and control participants have been observed on a minority of measures. More importantly, however, the clinical significance of these findings may be limited because cognitive functioning overwhelmingly falls within the normal range when compared against normative data. In spite of these observations, there seems to be a propensity to interpret any cognitive and/or brain difference(s) as a clinically significant abnormality. The implications of this situation are multiple, with consequences for scientific research, substance-abuse treatment, and public policy.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 11/2011; 37(3):586-608. · 6.99 Impact Factor
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    ABSTRACT: The Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative, funded by an R13 from the National Institute of Mental Health, seeks to enhance translational research in treatment development for impaired cognition in schizophrenia by developing tools from cognitive neuroscience into useful measures of treatment effects on behavior and brain function. An initial series of meetings focused on the selection of a new set of tasks from cognitive neuroscience for the measurement of treatment effects on specific cognitive and neural systems. Subsequent validation and optimization studies are underway and a subset of validated measures with well-characterized psychometric properties will be generally available in 2011. This article describes results of the first meeting of the second phase of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia, which seeks to develop imaging biomarkers and improved animal models to enhance translational research. In this meeting, we considered issues related to the use of methods such as functional magnetic resonance imaging, electroencephalography, magnetoencephalography, and transcranial magnetic simulation as biomarkers for treatment development. We explored the biological nature of the signals measured by each method, their validity and reliability as measures of cognition-related neural activity, potential confounds related to drug effects on the signal of interest, and conceptual, methodological, and pragmatic issues related to their use in preclinical, first into human, and multicenter phase II and III studies. This overview article describes the background and goals of the meeting together with a summary of the major issues discussed in more detail in the accompanying articles appearing in this issue of Biological Psychiatry.
    Biological psychiatry 07/2011; 70(1):7-12. · 8.93 Impact Factor
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    ABSTRACT: How similar are the experiences of social rejection and physical pain? Extant research suggests that a network of brain regions that support the affective but not the sensory components of physical pain underlie both experiences. Here we demonstrate that when rejection is powerfully elicited--by having people who recently experienced an unwanted break-up view a photograph of their ex-partner as they think about being rejected--areas that support the sensory components of physical pain (secondary somatosensory cortex; dorsal posterior insula) become active. We demonstrate the overlap between social rejection and physical pain in these areas by comparing both conditions in the same individuals using functional MRI. We further demonstrate the specificity of the secondary somatosensory cortex and dorsal posterior insula activity to physical pain by comparing activated locations in our study with a database of over 500 published studies. Activation in these regions was highly diagnostic of physical pain, with positive predictive values up to 88%. These results give new meaning to the idea that rejection "hurts." They demonstrate that rejection and physical pain are similar not only in that they are both distressing--they share a common somatosensory representation as well.
    Proceedings of the National Academy of Sciences 03/2011; 108(15):6270-5. · 9.74 Impact Factor
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    ABSTRACT: Deficits of cognitive-control in schizophrenia have been assumed to result from a single impairment that leads to widespread consequences. Contrary to this view, we hypothesized that different control processes operate at different stages of processing, and that only some of these processes may be impaired. We employed two selection tasks to test the hypothesis that patients with schizophrenia have deficits in selecting information in working memory (WM), but not in selecting perceptual information. In the "Ignore" task, which fosters perceptual selection, participants saw a cue to remember either red or blue words, followed by a memory-set (2 red, 2 blue), a brief delay, and then a probe. The "Suppress" task was similar, except the memory-set came before the instruction-cue, and hence selection had to occur in WM. We recorded reaction time and percentage errors for positive probes ("Valid"), and two kinds of negative probes, those that were supposed to have been dropped from WM ("Lures") and those that had not appeared in the memory-set ("Controls"). Compared to healthy controls, patients were impaired in the Suppress but not the Ignore task. This dissociation implies that there are two different selection mechanisms.
    Schizophrenia Research 01/2011; 126(1-3):132-7. · 4.59 Impact Factor
  • Phyllis Koenig, Edward E. Smith, Murray Grossman
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    ABSTRACT: We examined the interaction of content and process in categorizing novel semantic material. We taught patients with Alzheimer's disease (AD) and healthy age-matched seniors a category of plausible novel tools by similarity- and rule-based processes, and compared the results with our previous parallel study of categorization of novel animals, in which AD patients were selectively impaired at rule-based categorization. AD patients demonstrated learning in the novel tool study; however, in contrast to the novel animal study, they were impaired in similarity-based as well as rule-based categorization relative to healthy seniors. Healthy seniors’ categorization strategies reflected process irrespective of category content; they frequently attended to a single feature following similarity-based training, and always attended to all requisite features following rule-based training. AD patients’ categorization strategies, in contrast, reflected category content; they frequently attended to a single feature when categorizing novel animals by either categorization process, but rarely did so when categorizing novel tools. AD patients’ ability to categorize novel tools correlated with preserved recognition memory, a pattern not found in the novel animal study. The category-specific role of memory, along with AD patients’ performance profile, suggests content-specific distinctions between the categories. We posit that tool features are relatively arbitrary, placing greater demands on memory, while prior knowledge about animals such as constraints on appearance and feature diagnosticity facilitates the assimilation of novel animals into semantic memory. The results suggest that categorization processes are sensitive to category content, which influences AD patients’ success at acquiring a new category.
    Neuropsychologia. 01/2010;
  • 10/2009; , ISBN: 9780470478509
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    Michael S Franklin, John Jonides, Edward E Smith
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    ABSTRACT: Despite a great deal of research on the processing of numerical magnitude (e.g., the quantity denoted by the number 5), few studies have investigated how this magnitude information relates to the ordinal properties of numbers (e.g., the fact that 5 is the fifth integer). In the present study, we investigated order-related processing of numbers, as well as months of the year, with a novel ordering task to see whether the processing of order information differs from the processing of magnitude information. In Experiments 1 and 2, participants were shown three numbers (Experiment 1) or three months (Experiment 2) and were required to indicate whether the stimuli were in the correct order. In Experiment 3, participants were again shown three numbers; however, now they were instructed to indicate whether the three numbers were ordered in a forward, backward, or mixed direction. Whereas number comparison tasks typically reveal distance effects (comparisons become easier with increased distance between two numbers), these three experiments reveal a different pattern of results. There were reverse distance effects when the stimuli crossed a boundary (i.e., when numbers crossed a decade or months crossed the year boundary) and no effect of distance when the stimuli did not cross a boundary (i.e., when numbers were within a decade and months were within the January-December calendar year). These data suggest that additional mechanisms are involved in the processing of order information: a scanning mechanism and a long-term memory checking mechanism.
    Memory & Cognition 08/2009; 37(5):644-54. · 1.92 Impact Factor
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    ABSTRACT: We present a functional MRI experiment investigating the neural basis of feature-based attention in humans using the Stroop task. Cortical areas specifically involved in color processing and word reading were first identified in individual participants using independent tests. These areas were then probed during the Stroop task (in which participants must selectively attend to the font color of a word while ignoring the word itself). We found that activation in functionally defined color areas increased during the task relative to a neutral color-naming task while activation in functionally defined word areas decreased. These results are consistent with a biased competition model of feature-based attention in which the processing of attended features is enhanced and the processing of ignored features is suppressed.
    Journal of Neuroscience 01/2009; 28(51):13786-92. · 6.91 Impact Factor
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    ABSTRACT: This overview describes the goals and objectives of the third conference conducted as part of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative. This third conference was focused on selecting specific paradigms from cognitive neuroscience that measured the constructs identified in the first CNTRICS meeting, with the goal of facilitating the translation of these paradigms into use in clinical trials contexts. To identify such paradigms, we had an open nomination process in which the field was asked to nominate potentially relevant paradigms and to provide information on several domains relevant to selecting the most promising tasks for each construct (eg, construct validity, neural bases, psychometrics, availability of animal models). Our goal was to identify 1-2 promising tasks for each of the 11 constructs identified at the first CNTRICS meeting. In this overview article, we describe the on-line survey used to generate nominations for promising tasks, the criteria that were used to select the tasks, the rationale behind the criteria, and the ways in which breakout groups worked together to identify the most promising tasks from among those nominated. This article serves as an introduction to the set of 6 articles included in this special issue that provide information about the specific tasks discussed and selected for the constructs from each of 6 broad domains (working memory, executive control, attention, long-term memory, perception, and social cognition).
    Schizophrenia Bulletin 12/2008; 35(1):109-14. · 8.49 Impact Factor
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    ABSTRACT: This overview describes the generation and development of the ideas that led to the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative. It also describes the organization, process, and products of the first meeting. The CNTRICS initiative involves a series of three conferences that will systematically address barriers to translating paradigms developed in the basic animal and human cognitive neuroscience fields for use in translational research aimed at developing novel treatments for cognitive impairments in schizophrenia. The articles in this special section report on the results of the first conference, which used a criterion-based consensus-building process to develop a set of cognitive constructs to be targeted for translation efforts.
    Biological psychiatry 08/2008; 64(1):4-10. · 8.93 Impact Factor

Publication Stats

4k Citations
562 Downloads
3k Views
309.95 Total Impact Points

Institutions

  • 2005–2013
    • University of Pennsylvania
      • Department of Neurology
      Philadelphia, PA, United States
  • 2004–2013
    • Columbia University
      • • Department of Psychology
      • • Department of Psychiatry
      • • Department of Neurology
      New York City, New York, United States
  • 2009
    • University of California, Santa Barbara
      Santa Barbara, California, United States
  • 1987–2009
    • University of Michigan
      • Department of Psychology
      Ann Arbor, MI, United States
  • 2007–2008
    • Hospital of the University of Pennsylvania
      • Department of Neurology
      Philadelphia, Pennsylvania, United States
    • University of California, San Diego
      • Department of Psychology
      San Diego, CA, United States
  • 2006–2007
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
    • Michigan State University
      East Lansing, Michigan, United States
  • 1981–1991
    • Massachusetts Institute of Technology
      Cambridge, Massachusetts, United States