Institute of Cognitive Neuroscience, University College London, London WC1N 3AZ, United Kingdom,
Division of Psychiatry, University College London, London W1T 7NF, United Kingdom.
J Neurosci. 2018 Oct 31;38(44):9471-9485. doi: 10.1523/JNEUROSCI.3163-17.2018. Epub 2018 Sep 5.
Subjects with a diagnosis of schizophrenia (Scz) overweight unexpected evidence in probabilistic inference: such evidence becomes "aberrantly salient." A neurobiological explanation for this effect is that diminished synaptic gain (e.g., hypofunction of cortical NMDARs) in Scz destabilizes quasi-stable neuronal network states (or "attractors"). This attractor instability account predicts that (1) Scz would overweight unexpected evidence but underweight consistent evidence, (2) belief updating would be more vulnerable to stochastic fluctuations in neural activity, and (3) these effects would correlate. Hierarchical Bayesian belief updating models were tested in two independent datasets ( = 80 male and = 167 female) comprising human subjects with Scz, and both clinical and nonclinical controls (some tested when unwell and on recovery) performing the "probability estimates" version of the beads task (a probabilistic inference task). Models with a standard learning rate, or including a parameter increasing updating to "disconfirmatory evidence," or a parameter encoding belief instability were formally compared. The "belief instability" model (based on the principles of attractor dynamics) had most evidence in all groups in both datasets. Two of four parameters differed between Scz and nonclinical controls in each dataset: belief instability and response stochasticity. These parameters correlated in both datasets. Furthermore, the clinical controls showed similar parameter distributions to Scz when unwell, but were no different from controls once recovered. These findings are consistent with the hypothesis that attractor network instability contributes to belief updating abnormalities in Scz, and suggest that similar changes may exist during acute illness in other psychiatric conditions. Subjects with a diagnosis of schizophrenia (Scz) make large adjustments to their beliefs following unexpected evidence, but also smaller adjustments than controls following consistent evidence. This has previously been construed as a bias toward "disconfirmatory" information, but a more mechanistic explanation may be that in Scz, neural firing patterns ("attractor states") are less stable and hence easily altered in response to both new evidence and stochastic neural firing. We model belief updating in Scz and controls in two independent datasets using a hierarchical Bayesian model, and show that all subjects are best fit by a model containing a belief instability parameter. Both this and a response stochasticity parameter are consistently altered in Scz, as the unstable attractor hypothesis predicts.
患有精神分裂症 (Scz) 的受试者在概率推理中对意外证据的权重出乎意料:这种证据变得“异常突出”。这种效应的神经生物学解释是,Scz 中的突触增益降低(例如,皮质 NMDA 受体功能低下)会使准稳定神经元网络状态(或“吸引子”)不稳定。这种吸引子不稳定性解释预测,(1)Scz 会过度重视意外证据,但轻视一致证据,(2)信念更新更容易受到神经活动的随机波动的影响,(3)这些影响会相关。在两个独立的数据集(= 80 名男性和= 167 名女性)中,使用包含精神分裂症患者和临床及非临床对照的分层贝叶斯信念更新模型(一些在不适和康复时进行“概率估计”版本的珠子任务(概率推理任务))进行了测试。与标准学习率的模型或包含增加对“否定证据”更新的参数的模型或包含编码信念不稳定性的参数的模型进行了正式比较。在两个数据集的所有组中,基于吸引子动力学原理的“信念不稳定性”模型具有最多的证据。在每个数据集的 Scz 和非临床对照之间,有四个参数中的两个不同:信念不稳定性和反应随机性。这些参数在两个数据集之间相关。此外,临床对照在不适时与 Scz 具有相似的参数分布,但一旦康复,与对照无差异。这些发现与吸引子网络不稳定性导致 Scz 中信念更新异常的假设一致,并表明在其他精神疾病的急性疾病中可能存在类似的变化。患有精神分裂症 (Scz) 的受试者在出现意外证据后会对其信念进行大幅调整,但在出现一致证据后调整幅度也小于对照。这以前被解释为对“否定”信息的偏见,但更机械的解释可能是,在 Scz 中,神经放电模式(“吸引子状态”)不太稳定,因此容易受到新证据和随机神经放电的影响而改变。我们使用分层贝叶斯模型对两个独立的数据集进行 Scz 和对照的信念更新建模,并表明所有受试者都通过包含信念不稳定性参数的模型拟合得最好。正如不稳定吸引子假设所预测的那样,该模型和反应随机性参数在 Scz 中都发生了一致的改变。