Contributions of Feature Binding During Encoding and Functional Connectivity of the Medial Temporal Lobe Structures to Episodic Memory Deficits Across the Prodromal and First-Episode Phases of Schizophrenia

Abstract

Patients with and at risk for psychosis may have difficulty using associative strategies to facilitate episodic memory encoding and recall. In parallel studies, patients with first-episode schizophrenia (n = 27) and high psychosis risk (n = 28) compared with control participants (n = 22 and n = 20, respectively) underwent functional MRI during a remember-know memory task. Psychophysiological interaction analyses, using medial temporal lobe (MTL) structures as regions of interest, were conducted to measure functional connectivity patterns supporting successful episodic memory. During encoding, patients with first-episode schizophrenia demonstrated reduced functional coupling between MTL regions and regions involved in stimulus representations, stimulus selection, and cognitive control. Relative to control participants and patients with high psychosis risk who did not convert to psychosis, patients with high psychosis risk who later converted to psychosis also demonstrated reduced connectivity between MTL regions and auditory-verbal and visual-association regions. These results suggest that episodic memory deficits in schizophrenia are related to inefficient recruitment of cortical connections involved in associative memory formation; such deficits precede the onset of psychosis among those individuals at high clinical risk.

How Schizophrenia Develops: Cognitive and Brain Mechanisms Underlying Onset of Psychosis

“…These findings converge with evidence of differential impairment of episodic memory in schizophrenia, such that there is a deficit in deep or relational encoding, reducing contextual referencing of memories and making patients relatively more reliant on familiarity-based processes [41–44]. A similar deficit in episodic memory has been observed in CHR subjects [41], and those who later convert to psychosis have been found to show learning and memory deficits on clinical neuropsychological tests [45, 46]. The effect sizes on these measures in CHR cases who later convert are somewhat smaller than those seen in first-episode schizophrenia [41, 46], suggesting progression of episodic memory deficits from the prodromal to fully psychotic phases.…”

“…A similar deficit in episodic memory has been observed in CHR subjects [41], and those who later convert to psychosis have been found to show learning and memory deficits on clinical neuropsychological tests [45, 46]. The effect sizes on these measures in CHR cases who later convert are somewhat smaller than those seen in first-episode schizophrenia [41, 46], suggesting progression of episodic memory deficits from the prodromal to fully psychotic phases. However, whether there is progressive deterioration in episodic memory within CHR subjects who develop psychosis has not yet been examined.…”

“…Further, structural variations in the paracingulate sulcus, located in the medial PFC, correlate with individual differences in performance on reality monitoring tasks [38]. These findings converge with evidence of differential impairment of episodic memory in schizophrenia, such that there is a deficit in deep or relational encoding, reducing contextual referencing of memories and making patients relatively more reliant on familiarity-based processes [41–44]. A similar deficit in episodic memory has been observed in CHR subjects [41], and those who later convert to psychosis have been found to show learning and memory deficits on clinical neuropsychological tests [45, 46].…”

Sustained versus instantaneous connectivity differentiates cognitive functions of processing speed and episodic memory

“…Strength of traditional functional connectivity has been linked to performance in episodic memory tasks in aging populations (Fjell et al, 2015; Fjell et al, 2016), bipolar disorder (Oertel-Knochel et al, 2015), and schizophrenia (Haut et al, 2015). In a study measuring availability of dopamine D2 receptors, caudate-hippocampal connectivity was associated with D2 receptor availability and episodic memory, but not processing speed (Nyberg et al, 2016).…”

Memory systems in schizophrenia: Modularity is preserved but deficits are generalized

“…Variations in the level of impairment across particular tasks or components of tasks may be related to their reliance on this generalized ability. For example, recollection-based episodic memory is relatively more impaired than familiarity-based episodic memory in schizophrenia (Haut et al, 2014; van Erp et al, 2008). These findings were replicated in this sample, with SCZ showing impairment on R responses [F(3,1127)=3.99, p=.008] and not K responses [F(3,1127)=.2750, p=.84] on the R-K task.…”