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1.  Facilitation of Relational Learning in Schizophrenia 
Behavioral sciences  2013;3(2):10.3390/bs3020206.
Abnormal hippocampal function likely contributes to relational learning deficits observed in schizophrenia. It is unknown whether these deficits can be attenuated with a training intervention. The purpose of this project was to determine if training could facilitate relational learning of the transverse patterning task in schizophrenia. Healthy and schizophrenia subjects completed a version of transverse patterning that incorporated training. The majority of subjects with schizophrenia successfully learned transverse patterning when provided with training. A subgroup (approximately 25%) of schizophrenia subjects showed no tendency to learn with training. These results were replicated in a second study with a separate cohort and different stimuli. This study illustrates that relational learning of the transverse patterning can be facilitated in schizophrenia with training.
doi:10.3390/bs3020206
PMCID: PMC3826982  PMID: 24244873
schizophrenia; relational learning; training; transverse patterning; hippocampus; medial temporal lobe; memory
2.  Facilitation of Relational Learning in Schizophrenia  
Behavioral Sciences  2013;3(2):206-216.
Abnormal hippocampal function likely contributes to relational learning deficits observed in schizophrenia. It is unknown whether these deficits can be attenuated with a training intervention. The purpose of this project was to determine if training could facilitate relational learning of the transverse patterning task in schizophrenia. Healthy and schizophrenia subjects completed a version of transverse patterning that incorporated training. The majority of subjects with schizophrenia successfully learned transverse patterning when provided with training. A subgroup (approximately 25%) of schizophrenia subjects showed no tendency to learn with training. These results were replicated in a second study with a separate cohort and different stimuli. This study illustrates that relational learning of the transverse patterning can be facilitated in schizophrenia with training.
doi:10.3390/bs3020206
PMCID: PMC3826982  PMID: 24244873
schizophrenia; relational learning; training; transverse patterning; hippocampus; medial temporal lobe; memory
3.  Spatial Memory Deficits in a Virtual Reality Eight-Arm Radial Maze in Schizophrenia 
Schizophrenia Research  2011;135(1-3):84-89.
Learning and memory impairments are present in schizophrenia (SZ) throughout the illness course and predict psychosocial function. Abnormalities in prefrontal and hippocampal function are thought to contribute to SZ deficits. The radial arm maze (RAM) is a test of spatial learning and memory in rodents that relies on intact prefrontal and hippocampal function. The goal of the present study was to investigate spatial learning in SZ using a virtual RAM. Thirty-three subjects with SZ and thirty-nine healthy controls (HC) performed ten trials of a virtual RAM task. Subjects attempted to learn to retrieve four rewards each located in separate arms. As expected, subjects with SZ used more time and traveled more distance to retrieve rewards, made more reference (RM) and working memory (WM) errors, and retrieved fewer rewards than HC. It is important to note that the SZ group did learn but did not reach the level of HC. Whereas RM errors decreased across trials in the SZ group, WM errors did not. There were no significant relationships between psychiatric symptom severity and maze performance. To our knowledge, use of a virtual 8-arm radial maze task in SZ to assess spatial learning is novel. Impaired virtual RAM performance in SZ is consistent with studies that examined RAM performance in animal models of SZ. Results provide further support for compromised prefrontal and hippocampal function underlying WM and RM deficits in SZ. The virtual RAM task could help bridge preclinical and clinical research for testing novel drug treatments of SZ.
doi:10.1016/j.schres.2011.11.014
PMCID: PMC3288352  PMID: 22154760
radial arm maze; reference memory; working memory; schizophrenia; spatial learning; memory
4.  Repetition of letter strings leads to activation of and connectivity with word-related regions 
Neuroimage  2011;59(3):2839-2849.
Individuals learn to read by gradually recognizing repeated letter combinations. However, it is unclear how or when neural mechanisms associated with repetition of basic stimuli (i.e., strings of letters) shift to involvement of higher-order language networks. The present study investigated this question by repeatedly presenting unfamiliar letter strings in a one-back matching task during an hour-long period. Activation patterns indicated that only brain areas associated with visual processing were activated during the early period, but additional regions that are usually associated with semantic and phonological processing in inferior frontal gyrus were recruited after stimuli became more familiar. Changes in activation were also observed in bilateral superior temporal cortex, also suggestive of a shift toward a more language-based processing strategy. Connectivity analyses reveal two distinct networks that correspond to phonological and visual processing, which may reflect the indirect and direct routes of reading. The phonological route maintained a similar degree of connectivity throughout the experiment, whereas visual areas increased connectivity with language areas as stimuli became more familiar, suggesting early recruitment of the direct route. This study provides insight about plasticity of the brain as individuals become familiar with unfamiliar combinations of letters (i.e., words in a new language, new acronyms) and has implications for engaging these linguistic networks during development of language remediation therapies.
doi:10.1016/j.neuroimage.2011.09.047
PMCID: PMC3254793  PMID: 21982931
letter strings; fMRI; connectivity; reading; learning; plasticity
5.  Neural Changes Associated With Relational Learning in Schizophrenia 
Schizophrenia Bulletin  2010;36(3):496-503.
Relational learning, which is learning the relationship among items, is impaired in schizophrenia but can be improved with training. This study investigated neural changes with functional magnetic resonance imaging before and after training on a relational learning task in schizophrenia and healthy control subjects. Despite their acquiring similar relational learning performance, the groups exhibited different neural activation patterns before and following training. Controls engaged regions within the relational learning network that included frontal, parietal, and medial temporal lobe, before and following training. Controls also exhibited activation reductions in region and spatial extent with relational learning proficiency, a commonly observed phenomenon in successful learning. In contrast, subjects with schizophrenia displayed no positive activations compared with the control condition before training. After training, subjects with schizophrenia displayed bilateral inferior parietal region activation as predicted. Contrary to hypothesis, hippocampal activation was not observed following training in schizophrenia. These findings suggest that the parietal lobe may be receptive to cognitive training interventions and that successful relational learning may be achieved in schizophrenia through the use of alternative extrahippocampal brain regions.
doi:10.1093/schbul/sbq037
PMCID: PMC2879675  PMID: 20418447
fMRI; hippocampus; training; transverse patterning; brain; relational memory
6.  Word and Letter String Processing Networks in Schizophrenia: Evidence for Anomalies and Compensation 
Brain and language  2008;107(2):158-166.
Imaging studies show that in normal language correlated activity between anterior and posterior brain regions increases as the linguistic and semantic content (i.e., from false fonts, letter strings, pseudo words, to words) of stimuli increase. In schizophrenia however, disrupted functional connectivity between frontal and posterior brain regions has been frequently reported and these disruptions may change the nature of language organization. We characterized basic linguistic operations in word and letter string processing in a region-of-interest network using structural equation modeling (SEM). Healthy volunteers and volunteers with schizophrenia performed an fMRI one-back matching task with real words and consonant letter strings. We hypothesized that left hemisphere network dysfunction in schizophrenia would be present during processes dealing with linguistic/semantic content. The modeling results suggest aberrant left hemisphere function in schizophrenia, even in tasks requiring minimal access to language. Alternative mechanisms included increases in right hemisphere involvement and increased top-down influence from frontal to posterior regions.
doi:10.1016/j.bandl.2008.04.001
PMCID: PMC2599869  PMID: 18829095
Schizophrenia and language; Lateralization; Lexical-semantic processing; Imaging; Effective Connectivity; Modeling

Results 1-6 (6)