Functional and Neuroanatomic Specificity of Episodic Memory Dysfunction in Schizophrenia

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 MEASURESBehavioral 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 (F 1,107 = 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 RELEVANCEIn 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.

Episodic memory functions in first episode psychosis and clinical high risk individuals

“…As in previous studies of chronic patients (Ragland et al 2012a, 2012b, 2015), discriminability following both item and relational encoding was impaired for FE participants. The FE group also showed pronounced recollection deficits following item as well as relational encoding, the same pattern previously noted for patients with long-term illness (Ragland et al 2012a, 2012b, 2015). One area of difference was familiarity-based retrieval.…”

“…In addition to CHR participants, we examined patients during a first episode of psychosis (FE). Most previous studies (e.g., Achim & LePage, 2003; Ragland et al, 2015; Williams et al 2010) examined more chronically ill patients. By investigating FE participants we aim to discover if the encoding and retrieval deficits associated with chronic schizophrenia are also apparent early in the illness.…”

Cortical contributions to impaired contour integration in schizophrenia

“…It should be noted that the lack of greater activation for the CON versus SCZ group is unlikely to be an artifact, as greater activation in CON than SCZ was seen during working and relational memory paradigms that were completed during the same scanning session (Ragland et al, in Press; Sheffield et al, 2015). However, a fuller exploration of the effects of higher level visual processing on JOVI performance was precluded by the lack of sufficient data for analysis of activity in bilateral IFG pars triangularis and parietal angular gyrus, as described in Footnote 1.…”

The Relational and Item-Specific Encoding Task in Mild Cognitive Impairment and Alzheimer Disease

“…The Relational and Item-Specific Encoding task (RISE) was developed to directly address memory after these different types of encoding processes [5,6]. This computer-based paradigm manipulates encoding by having participants actively utilize 2 methods for analyzing visual pictured stimuli of real-world entities: an item-specific and a relational method.…”

“…After 30 min, recognition memory for all of the items or pairs of items is assessed and d′ scores for item-encoded or relationally encoded stimuli are derived. In a series of studies, the test was shown to have acceptable test-retest reliability, to consistently activate medial temporal lobe (MTL) subregions in fMRI studies, and to yield profiles of performance in schizophrenia characterized by disproportionate impairments in memory after relational encoding as well as hippocampal and dorsolateral prefrontal activation failures [5,6]. …”