Functional and Neuroanatomic Specificity of Episodic Memory Dysfunction in Schizophrenia: A Functional Magnetic Resonance Imaging Study of the Relational and Item-Specific Encoding Task - PubMed (original) (raw)

doi: 10.1001/jamapsychiatry.2015.0276.

Charan Ranganath 2, Michael P Harms 3, Deanna M Barch 3, James M Gold 4, Evan Layher 1, Tyler A Lesh 1, Angus W MacDonald 3rd 5, Tara A Niendam 1, Joshua Phillips 1, Steven M Silverstein 6, Andrew P Yonelinas 2, Cameron S Carter 7

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Functional and Neuroanatomic Specificity of Episodic Memory Dysfunction in Schizophrenia: A Functional Magnetic Resonance Imaging Study of the Relational and Item-Specific Encoding Task

J Daniel Ragland et al. JAMA Psychiatry. 2015 Sep.

Abstract

Importance: Individuals with schizophrenia can encode item-specific information to support familiarity-based recognition but are disproportionately impaired encoding interitem relationships (relational encoding) and recollecting information. The Relational and Item-Specific Encoding (RiSE) paradigm has been used to disentangle these encoding and retrieval processes, which may depend on specific medial temporal lobe (MTL) and prefrontal cortex (PFC) subregions. Functional magnetic resonance (fMRI) imaging during RiSE task performance could help to specify dysfunctional neural circuits in schizophrenia that can be targeted for interventions to improve memory and functioning in the illness.

Objectives: To use fMRI to test the hypothesis that schizophrenia disproportionately affects MTL and PFC subregions during relational encoding and retrieval relative to item-specific memory processes, and to use fMRI results from healthy individuals serving as controls to establish neural construct validity for RiSE.

Design, setting, and participants: This multisite, case-control, cross-sectional fMRI study was conducted between November 1, 2010, and May 30, 2012, at 5 Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia sites. The final sample included 52 outpatients with clinically stable schizophrenia and 57 demographically matched healthy control participants. Data analysis was performed between February 1, 2013, and May 30, 2014.

Main outcomes and measures: Behavioral performance speed and accuracy (d') on item recognition and associative recognition tasks. Voxelwise statistical parametric maps for a priori MTL and PFC regions of interest to test activation differences between relational and item-specific memory during encoding and retrieval.

Results: Item recognition was disproportionately impaired in patients with schizophrenia relative to healthy control participants following relational encoding (F1,107 = 4.7; P = .03). The differential deficit was accompanied by reduced dorsolateral PFC activation during relational encoding in patients with schizophrenia compared with healthy control participants (z > 2.3; P < .05 corrected). Retrieval success (hits > misses) was associated with hippocampal activation in healthy control participants during relational item recognition and associative recognition conditions, and hippocampal activation was specifically reduced in schizophrenia for recognition of relational but not item-specific information (z > 2.3; P < .05 corrected).

Conclusions and relevance: In this unique, multisite fMRI study, results in the healthy control group supported RiSE construct validity by revealing expected memory effects in PFC and MTL subregions during encoding and retrieval. Comparison of schizophrenic and healthy control participants revealed disproportionate memory deficits in schizophrenia for relational vs item-specific information, accompanied by regionally and functionally specific deficits in dorsolateral PFC and hippocampal activation.

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Figures

Figure 1

Figure 1

Illustration of item-specific and relational test procedures and task stimuli. (A) Fifty-four object pairs were visually presented while participants made either item410 specific encoding responses (Left Panel) or relational encoding responses (Right Panel). Conditions alternated (ABAB) between 6 blocks of 9 trials each, with 4 s.instruction screens between blocks to minimize alternation demands and maintain task set. (B) During item recognition, 54 individual objects from each encoding condition (54 item-specific, 54 relational) were randomly presented with 54 new items, and participants indicated whether each item was “old”. (C) During associative recognition, the 27 original relational encoding object pairs were randomly presented with 27 object pairs that had been changed by pairing items from different relational encoding trials (e.g., the left object from trial 6 and right object from trial 13), and participants indicated whether each object pair had “changed”.

Figure 2

Figure 2

Performance accuracy (d’; mean + standard error of the mean) during (A) Item Recognition and (B) Associative Recognition tasks. Panel A reveals that item recognition was disproportionately impaired in patients, relative to controls, following relational encoding. Panel B reveals that associative recognition was significantly impaired in patients, relative to controls.

Figure 3

Figure 3

Panel A illustrates a surface rendering of left (top) and right hemisphere (bottom) PFC activation during relational versus item-specific encoding, separately for healthy comparison subjects (HC) and people with schizophrenia (SZ). Hotter colors reflect greater activation (range z = 2.3 to 6.0). Panel B illustrates significant group differences (HC – SZ) in DLPFC activation during relational versus item-specific encoding in the left (top) and right (bottom) hemisphere. Group differences are indicated in red, with hotter colors reflecting greater activation (range z = 2.3 to 6.0), and are overlaid on DLPFC (in green) and VLPFC (in blue) ROIs to illustrate the regional specificity of prefrontal dysfunction in SZ. Surface renderings performed with Caret (5.61) software (

http://brainvis.wustl.edu/wiki/index.php/Caret:About

)

Figure 4

Figure 4

Panel A illustrates hippocampal activation during retrieval success (hits – misses) following relational encoding for the item recognition task. The top panel reveals results separately for HC (left) and SZ groups (right). The significant group difference (HC>SZ) is illustrated in the bottom figure. Panel B illustrates hippocampal activation during retrieval success (hits – misses) following relational encoding for the associative recognition task. The top panel reveals results separately for HC (left figure) and SZ group (right figure). For this task, there were no significant between-group differences in hippocampal activation. As in Figure 3, hotter colors reflect greater activation (range z = 2.3 to 6.0).

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References

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