Qualitatively Different Delay-Dependent Working Memory Distortions in People With Schizophrenia and Healthy Control Participants.

BACKGROUND: Impairments in working memory (WM) have been well documented in people with schizophrenia (PSZ). However, these quantitative WM impairments can often be explained by nonspecific factors, such as impaired goal maintenance. Here, we used a spatial orientation delayed response task to explore a qualitative difference in WM dynamics between PSZ and healthy control participants (HCs). More specifically, we took advantage of the discovery that WM representations may drift either toward or away from previous trial targets (serial dependence). We tested the hypothesis that WM representations would drift toward the previous trial target in HCs but away from the previous trial target in PSZ. METHODS: We assessed serial dependence in PSZ (n = 31) and HCs (n = 25) using orientation as the to-be-remembered feature and memory delays lasting from 0 to 8 seconds. Participants were asked to remember the orientation of a teardrop-shaped object and reproduce the orientation after a delay period of varying length. RESULTS: Consistent with prior studies, we found that current trial memory representations were less precise in PSZ than in HCs. We also found that WM for the current trial orientation drifted toward the previous trial orientation in HCs (representational attraction) but drifted away from the previous trial orientation in PSZ (representational repulsion). CONCLUSIONS: These results demonstrate a qualitative difference in WM dynamics between PSZ and HCs that cannot be easily explained by nuisance factors such as reduced effort. Most computational neuroscience models also fail to explain these results because they maintain information solely by means of sustained neural firing, which does not extend across trials. The results suggest a fundamental difference between PSZ and HCs in longer-term memory mechanisms that persist across trials, such as short-term potentiation and neuronal adaptation.

Sustained attention deficits in schizophrenia: Effect of memory load on the Identical Pairs Continuous Performance Test.

Background: Sustained attention and vigilance impairments are well documented in people with schizophrenia (PSZ). The processes implicated in this impairment remain unclear. Here we investigated whether vigilance performance varied as a function of working memory load, and also examined the role of attentional lapsing that might arise from a loss of task set resulting in mind wandering. Method: We examined Continuous Performance Test Identical Pairs (CPT-IP) data from a cumulative sample of 247 (PSZ) and 238 healthy control (HC) participants collected over a series of studies. Results: PSZ performed more poorly that HC across conditions with signal/noise discrimination (d') decreasing with increasing working memory load across both groups However, there was a significant interaction of group and load suggesting that performance of PSZ was more negatively impacted by increasing load. We also found that PSZ has a significantly higher rate of attention lapsing than did HC. Discussion: Our results suggest that difficulties maintaining task set and working memory limitations are implicated in the impairments observed on the Identical Pairs CPT. Difficulties with task set maintenance appear to explain the majority of between-group variance, with a more subtle impact of increasing working memory load.

Phenomenological and Cognitive Features Associated With Auditory Hallucinations in Clinical and Nonclinical Voice Hearers.

BACKGROUND AND HYPOTHESES: Auditory verbal hallucinations (AVH) are central features of schizophrenia (SZ). However, AVH also occur in a small percentage of the general population who do not have a need for care, termed nonclinical voice hearers (NCVH). We sought to determine the degree to which the experience of AVH was similar in NCVH and in people with schizophrenia (PSZ) and evaluate the degree to which NCVH shared other features of SZ such as delusional beliefs, cognitive impairment, and negative symptoms. STUDY DESIGN: We recruited 76 people with a DSM-V diagnosis of SZ/schizoaffective disorder (PSZ; 49 with current AVH, 27 without), 48 NCVH, and 51 healthy controls. Participants received a broad battery of clinician-administered and self-report symptom assessments and a focused cognitive assessment. STUDY RESULTS: The AVH of NCVH and PSZ shared very similar sensory features. NCVH experienced less distress, had greater control over their AVH, and, unlike PSZ, rarely heard 2 voices speaking to each other. NCVH demonstrated a wide range of deeply held unusual beliefs, but reported less paranoia, and fewer first-rank symptoms such as passivity and alterations in self-experience. NCVH showed no evidence of cognitive deficits or negative symptoms. CONCLUSIONS: The AVH in NCVH and PSZ demonstrate important similarities as well as clear differences. Specific features, rather than the presence, of AVH appear to determine the need for care. NCVH do not share the cognitive and motivational deficits seen in PSZ. These results suggest that AVH and unusual beliefs can be separated from the broader phenotype of SZ.

Qualitatively different delay-dependent working memory distortions in people with schizophrenia and healthy control subjects.

Background: Impairments in working memory(WM) have been well-documented in people with schizophrenia(PSZ). However, these quantitative WM impairments can often be explained by nonspecific factors, such as impaired goal maintenance. Here, we used a spatial orientation delayed-response task to explore a qualitative difference in WM dynamics between PSZ and healthy control subjects(HCS). Specifically, we took advantage of the discovery that WM representations may drift either toward or away from previous-trial targets(serial dependence). We tested the hypothesis that WM representations drift toward the previous-trial target in HCS but away from the previous-trial target in PSZ. Methods: We assessed serial dependence in PSZ(N=31) and HCS(N=25), using orientation as the to-be-remembered feature and memory delays from 0 to 8s. Participants were asked to remember the orientation of a teardrop-shaped object and reproduce the orientation after a varying delay period. Results: Consistent with prior studies, we found that current-trial memory representations were less precise in PSZ than in HCS. We also found that WM for the current-trial orientation drifted toward the previous-trial orientation in HCS(representational attraction) but drifted away from the previous-trial orientation in PSZ(representational repulsion). Conclusions: These results demonstrate a qualitative difference in WM dynamics between PSZ and HCS that cannot easily be explained by nuisance factors such as reduced effort. Most computational neuroscience models also fail to explain these results, because they maintain information solely by means of sustained neural firing, which does not extend across trials. The results suggest a fundamental difference between PSZ and HCS in longer-term memory mechanisms that persist across trials, such as short-term potentiation and neuronal adaptation.

Relating Glutamate, Conditioned, and Clinical Hallucinations via 1H-MR Spectroscopy.

BACKGROUND AND HYPOTHESIS: Hallucinations may be driven by an excessive influence of prior expectations on current experience. Initial work has supported that contention and implicated the anterior insula in the weighting of prior beliefs. STUDY DESIGN: Here we induce hallucinated tones by associating tones with the presentation of a visual cue. We find that people with schizophrenia who hear voices are more prone to the effect and using computational modeling we show they overweight their prior beliefs. In the same participants, we also measured glutamate levels in anterior insula, anterior cingulate, dorsolateral prefrontal, and auditory cortices, using magnetic resonance spectroscopy. STUDY RESULTS: We found a negative relationship between prior-overweighting and glutamate levels in the insula that was not present for any of the other voxels or parameters. CONCLUSIONS: Through computational psychiatry, we bridge a pathophysiological theory of psychosis (glutamate hypofunction) with a cognitive model of hallucinations (prior-overweighting) with implications for the development of new treatments for hallucinations.