Auditory Working Memory Impairments in Individuals at Familial High Risk for Schizophrenia

Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA.
Neuropsychology (Impact Factor: 3.27). 05/2012; 26(3):288-303. DOI: 10.1037/a0027970
Source: PubMed


The search for predictors of schizophrenia has accelerated with a growing focus on early intervention and prevention of psychotic illness. Studying nonpsychotic relatives of individuals with schizophrenia enables identification of markers of vulnerability for the illness independent of confounds associated with psychosis. The goal of these studies was to develop new auditory continuous performance tests (ACPTs) and evaluate their effects in individuals with schizophrenia and their relatives.
We carried out two studies of auditory vigilance with tasks involving working memory (WM) and interference control with increasing levels of cognitive load to discern the information-processing vulnerabilities in a sample of schizophrenia patients, and two samples of nonpsychotic relatives of individuals with schizophrenia and controls. Study 1 assessed adults (mean age = 41), and Study 2 assessed teenagers and young adults age 13-25 (M = 19).
Patients with schizophrenia were impaired on all five versions of the ACPTs, whereas relatives were impaired only on WM tasks, particularly the two interference tasks that maximize cognitive load. Across all groups, the interference tasks were more difficult to perform than the other tasks. Schizophrenia patients performed worse than relatives, who performed worse than controls. For patients, the effect sizes were large (Cohen's d = 1.5), whereas for relatives they were moderate (d = ~0.40-0.50). There was no age by group interaction in the relatives-control comparison except for participants <31 years of age.
Novel WM tasks that manipulate cognitive load and interference control index an important component of the vulnerability to schizophrenia.

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    • "divide attention and prevent counting, and presumably burden especially the cognitive processes of attention control. Following the original paradigm, we defined WM load as the number of letters between the cue and the target, while level of interference was defined as the number of distractors ( " Qs " and " As " ) embedded between the cue and the target (Seidman et al., 2012). Noticeably, the increase of load corresponds to the prolonged delay between the cue and the target, which has been previously shown to increase activity in left DLPFC (Barch et al., 1997), a load effect observed by the same research group in their other study using a parametric N-back task (Braver et al., 1997). "
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    ABSTRACT: Auditory attention and working memory (WM) allow for selection and maintenance of relevant sound information in our minds, respectively, thus underlying goal-directed functioning in everyday acoustic environments. It is still unclear whether these two closely coupled functions are based on a common neural circuit, or whether they involve genuinely distinct subfunctions with separate neuronal substrates. In a full factorial functional MRI (fMRI) design, we independently manipulated the levels of auditory-verbal WM load and attentional interference using modified Auditory Continuous Performance Tests. Although many frontoparietal regions were jointly activated by increases of WM load and interference, there was a double dissociation between prefrontal cortex (PFC) subareas associated selectively with either auditory attention or WM. Specifically, anterior dorsolateral PFC (DLPFC) and the right anterior insula were selectively activated by increasing WM load, whereas subregions of middle lateral PFC and inferior frontal cortex (IFC) were associated with interference only. Meanwhile, a superadditive interaction between interference and load was detected in left medial superior frontal cortex, suggesting that in this area, activations are not only overlapping, but reflect a common resource pool recruited by increased attentional and WM demands. Indices of WM-specific suppression of anterolateral non-primary auditory cortices (AC) and attention-specific suppression of primary AC were also found, possibly reflecting suppression/interruption of sound-object processing of irrelevant stimuli during continuous task performance. Our results suggest a double dissociation between auditory attention and working memory in subregions of anterior DLPFC vs. middle lateral PFC/IFC in humans, respectively, in the context of substantially overlapping circuits.
    Full-text · Article · Aug 2013 · NeuroImage
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    • "One explanation might be that awareness of cognitive problems differs from domain to domain and working memory problems may be easier and more obvious to recognize and report. Working memory problems are also marked in the pre-morbid stage of psychosis and feature heavily in family members, suggesting a genetic predisposition (Seidman et al. 2012). Longer experience with memory deficits, and also having experienced difficulties in a period prior to psychotic symptoms onset, may result in better awareness of this problem. "
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    ABSTRACT: Background People with a diagnosis of schizophrenia have limited metacognitive awareness of their symptoms. This is also evident for cognitive difficulties when neuropsychological assessments and self-reports are compared. Unlike for delusions and hallucinations, little attention has been given to factors that may influence the mismatch between objective and subjectively reported cognitive problems. Symptom severity, and also self-esteem and social functioning, can have an impact on cognitive problem perception and help to explain the gap between objective and subjective cognitive assessments in psychosis. Method One-hundred participants with a diagnosis of schizophrenia were recruited and assessed with a comprehensive neuropsychological battery, a measure of awareness of cognitive problems and measures of psychotic symptoms, social and behavioural functioning and self-esteem. Regression was used to investigate the influence of symptoms, social functioning and self-esteem, and patients with different levels of cognitive problem awareness were contrasted. Results Simple correlation analysis replicated the lack of association between objective cognitive measures and metacognitive awareness of cognitive problems. However, the results of the regression analyses highlight that self-esteem and negative symptoms predict metacognitive awareness. When significant predictors were controlled, individuals with better awareness had more impaired working memory but higher IQ. Conclusions Poor self-esteem and high negative symptoms are negatively associated with metacognitive awareness in people with schizophrenia. Interventions that aim to improve cognition should consider that cognitive problem reporting in people with schizophrenia correlates poorly with objective measures and is biased not only by symptoms but also by self-esteem. Future studies should explore the causal pathways using longitudinal designs.
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    ABSTRACT: Background: Schizophrenia and affective psychoses share several common biological origins, particularly genetic susceptibility. Kraepelin posited that differing clinical expressions in these disorders reflect different etiopathologies. We tested a neuropsychological component of this hypothesis by evaluating verbal memory and visual memory performance in nonpsychotic youth at familial risk for psychosis, taking into account contributions to memory dysfunction including executive processing and psychopathology. Methods: Teenage and young adults (ages 13-25) at familial high-risk (FHR) for schizophrenia (HR-SCZ, n=41) or affective psychosis (HR-AFF, n=24) were compared to community controls (CC, n=54) on verbal (Miller-Selfridge Context Memory) and visual (Rey-Osterrieth Complex Figure) memory tests in which the roles of strategy and contextual processing on distinct recall domains could be assessed. Effects of psychopathology, vigilance and working memory were investigated to determine their influence on memory performance. Results: HR-AFF and HR-SCZ exhibited similarly impaired memory profiles and elevated levels of psychopathology compared to CC. HR-SCZ were significantly impaired on both verbal memory and visual-spatial memory, while HR-AFF in verbal memory only. However, effect sizes, in the medium range, were largely comparable between the two HR groups. Deficits in verbal recall and in visual memory organization remained significant after adjustment for confounders. Conclusions: Youth at FHR for psychosis present relatively common memory deficits across both visual-spatial and verbal modalities that are not explained by current psychopathology, vigilance or working memory deficits. Deficits in organizing information to be recalled represent a promising trait of psychosis vulnerability.
    No preview · Article · Jan 2013 · Schizophrenia Research
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