[Show abstract][Hide abstract] ABSTRACT: List learning tasks are powerful clinical tools for studying memory, yet have been relatively underutilized within the functional imaging literature. This limits understanding of regions such as the Papez circuit that support memory performance in healthy, nondemented adults.
The current study characterized list learning performance in 40 adults who completed a semantic list learning task (SLLT) with a Brown-Peterson manipulation during functional magnetic resonance imaging (fMRI). Cued recall with semantic cues and recognition memory were assessed after imaging. Internal reliability, convergent, and discriminant validity were evaluated.
Subjects averaged 38% accuracy in recall (62% for recognition), with primacy but no recency effects observed. Validity and reliability were demonstrated by showing that the SLLT was correlated with the California Verbal Learning Test (CVLT), but not with executive functioning tests, and by high intraclass correlation coefficient across lists for recall (.91). fMRI measurements during encoding (vs. silent rehearsal) revealed significant activation in bilateral hippocampus, parahippocampus, and bilateral anterior and posterior cingulate cortex. Post hoc analyses showed increased activation in anterior and middle hippocampus, subgenual cingulate, and mammillary bodies specific to encoding. In addition, increasing age was positively associated with increased activation in a diffuse network, particularly frontal cortex and specific Papez regions for correctly recalled words. Gender differences were specific to left inferior and superior frontal cortex.
This is a clinically relevant list learning task that can be used in studies of groups for which the Papez circuit is damaged or disrupted, in mixed or crossover studies at imaging and clinical sites.
Eprint Link: http://www.tandfonline.com/eprint/PJmBWgaXtWcz5A7VBz8v/full
Journal of Clinical and Experimental Neuropsychology 10/2015; 37(8):816-33. DOI:10.1080/13803395.2015.1052732 · 2.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The endogenous opioid system, which alleviates physical pain, is also known to regulate social distress and reward in animal models. To test this hypothesis in humans (n=18), we used an μ-opioid receptor (MOR) radiotracer to measure changes in MOR availability in vivo with positron emission tomography during social rejection (not being liked by others) and acceptance (being liked by others). Social rejection significantly activated the MOR system (i.e., reduced receptor availability relative to baseline) in the ventral striatum, amygdala, midline thalamus and periaqueductal gray (PAG). This pattern of activation is consistent with the hypothesis that the endogenous opioids have a role in reducing the experience of social pain. Greater trait resiliency was positively correlated with MOR activation during rejection in the amygdala, PAG and subgenual anterior cingulate cortex (sgACC), suggesting that MOR activation in these areas is protective or adaptive. In addition, MOR activation in the pregenual ACC was correlated with reduced negative affect during rejection. In contrast, social acceptance resulted in MOR activation in the amygdala and anterior insula, and MOR deactivation in the midline thalamus and sgACC. In the left ventral striatum, MOR activation during acceptance predicted a greater desire for social interaction, suggesting a role for the MOR system in social reward. The ventral striatum, amygdala, midline thalamus, PAG, anterior insula and ACC are rich in MORs and comprise a pathway by which social cues may influence mood and motivation. MOR regulation of this pathway may preserve and promote emotional well being in the social environment.Molecular Psychiatry advance online publication, 20 August 2013; doi:10.1038/mp.2013.96.
[Show abstract][Hide abstract] ABSTRACT: Measures of cognitive dysfunction in Bipolar Disorder (BD) have identified state and trait dependent metrics. An influence of substance abuse (SUD) on BD has been suggested. This study investigates potential differential, additive, or interactive cognitive dysfunction in bipolar patients with or without a history of SUD. Two hundred fifty-six individuals with BD, 98 without SUD and 158 with SUD, and 97 Healthy Controls (HC) completed diagnostic interviews, neuropsychological testing, and symptom severity scales. The BD groups exhibited poorer performance than the HC group on most cognitive factors. The BD with SUD exhibited significantly poorer performance than BD without SUD in visual memory and conceptual reasoning/set-shifting. In addition, a significant interaction effect between substance use and depressive symptoms was found for auditory memory and emotion processing. BD patients with a history of SUD demonstrated worse visual memory and conceptual reasoning skills above and beyond the dysfunction observed in these domains among individuals with BD without SUD, suggesting greater impact on integrative, gestalt-driven processing domains. Future research might address longitudinal outcome as a function of BD, SUD, and combined BD/SUD to evaluate neural systems involved in risk for, and effects of, these illnesses.
Psychiatry Research 07/2012; 200(2-3). DOI:10.1016/j.psychres.2012.06.013 · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mild traumatic brain injury (mTBI) affects a significant number of combat veterans returning from Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF). Although resolution of mTBI symptoms is expected over time, some individuals continue to report lingering cognitive difficulties. This study examined the contributions of self-reported mTBI injury characteristics (e.g., loss of consciousness, post-traumatic amnesia) and psychiatric symptoms to both subjective and objective cognitive functioning in a sample of 167 OEF/OIF veterans seen in a TBI clinic. Injury characteristics were not associated with performance on neuropsychological tests but were variably related to subjective ratings of cognitive functioning. Psychiatric symptoms were highly prevalent and fully mediated most of the relationships between injury characteristics and cognitive ratings. This indicates that mTBI characteristics such as longer time since injury and loss of consciousness or post-traumatic amnesia can lead to increased perceived cognitive deficits despite having no objective effects on cognitive performance. Psychiatric symptoms were associated with both cognitive ratings and neuropsychological performance, illustrating the important role that psychiatric treatment can potentially play in optimizing functioning. Finally, subjective cognitive ratings were not predictive of neuropsychological performance once psychiatric functioning was statistically controlled, suggesting that neuropsychological assessment provides valuable information that cannot be gleaned from self-report alone.
Journal of the International Neuropsychological Society 03/2012; 18(3):576-84. DOI:10.1017/S1355617712000203 · 2.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background / Purpose:
This study examines whether females with MDD demonstrate poorer list learning and recall than healthy controls (HC), and related activation abnormalities.Female participants (HC= 16, MDD= 17) completed the Semantic List Learning Task (SLLT) during fMRI; after the scan, they were asked to recall material presented during the task. Analyses included between-group comparisons of encoding versus distraction blocks, and event-related analyses of encoded words that were subsequently recalled.
Although there were no significant differences in the overall recall between MDD and HC groups, there were significant differences in neural activation for the Encoding minus Distraction contrast such that the HC group exhibited greater activation in: right precuneus, middle and superior frontal gyri, and cerebellum; left superior temporal and postcentral gyri; and bilateral insula, inferior frontal gyrus, and dorsal anterior cingulate. For the same contrast, MDD exhibited greater left medial temporal and bilateral cuneus activation. In the event-related analyses, HC exhibited greater activation in the right posterior parahippocampal gyrus whereas MDD exhibited greater activation in the right caudate, right dorsal cingulate and left inferior frontal gyrus.Behavioral recall did not differ between groups, perhaps due to low statistical power, whereas fMRI data indicated that patients with MDD may not engage neurocircuitry underlying memory to the degree of healthy individuals. These findings may help explain memory complaints in MDD and future studies could examine larger samples, and take into account frequency, salience and valence of the stimuli.
66th Society of Biological Psychiatry Annual Meeting 2011; 06/2011
[Show abstract][Hide abstract] ABSTRACT: Questions have been raised about whether poor performance on memory tasks by individuals with major depressive disorder (MDD) might be the result of poor or variable effort or disease-related disruption of neural circuits supporting memory functions. The present study examined performance on a measure of task engagement and on an auditory memory task among 45 patients with MDD (M age = 47.82, SD = 19.55) relative to 32 healthy controls (HC; M age = 51.03, SD = 22.09). One-hundred percent of HC and MDD volunteers performed above the threshold for adequate effort on a formal measure of task engagement. The MDD subjects performed significantly more poorly than the HC subjects on an auditory learning and memory test. The present results suggest that auditory memory difficulties do occur among those with MDD and that decrements in performance in this group may be related to factors other than lack of effort.
[Show abstract][Hide abstract] ABSTRACT: Mild traumatic brain injury (mTBI) is not uncommon among Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) veterans, and many individuals within this group report lingering cognitive difficulties following their injury. For Department of Veterans Affairs clinicians, an accurate assessment of cognitive symptoms is important in providing appropriate clinical care. Although self-assessment is commonly employed to screen for difficulties in cognitive functioning, little is known about the accuracy of self-report in this population. This study collected cognitive, psychiatric, and self-report data from 105 OIF/OEF veterans with mTBI to examine the relationship between self-reported cognitive functioning and objective neuropsychological test performance. Additionally, clinicians who frequently work with OIF/OEF veterans were asked to predict the magnitude of these associations. Self-reported cognitive functioning was not significantly correlated with objective cognitive abilities, suggesting that objective neuropsychological testing should be used when cognitive weakness is suspected. Perceived cognitive deficits were associated with depression, anxiety, and posttraumatic stress disorder, illustrating the additional importance of adequate assessment and treatment of psychiatric symptoms. Clinicians tended to overestimate the association between self-report and test performance.
The Journal of Rehabilitation Research and Development 01/2010; 47(6):521-30. DOI:10.1682/JRRD.2009.11.0181 · 1.43 Impact Factor