New papers on the hyperfocusing hypothesis of cognitive dysfunction in schizophrenia

Luck, S. J., Hahn, B., Leonard, C. J., & Gold, J. M. (2019). The hyperfocusing hypothesis: A new account of cognitive dysfunction in schizophrenia. Schizophrenia Bulletin, 45, 991–1000. https://doi.org/10.1093/schbul/sbz063

Luck, S. J., Leonard, C. J., Hahn, B., & Gold, J. M. (2019). Is selective attention impaired in schizophrenia? Schizophrenia Bulletin, 45, 1001–1011. https://doi.org/10.1093/schbul/sbz045

The most distinctive symptoms of schizophrenia are hallucinations, delusions, and disordered thought/behavior. However, people with schizophrenia also typically have impairments in basic cognitive processes, such as attention and working memory, and the degree of cognitive dysfunction is a better predictor of long-term outcome than is the severity of the psychotic symptoms.

Researchers have tried to identify the nature of cognitive dysfunction in schizophrenia since the 1960s, and our collaborative research group has spent almost 20 years on this problem. We now have a well-supported theory, which we call the hyperfocusing hypothesis, and we recently published a pair of papers that review this theory. The first paper describes the hyperfocusing hypothesis in detail and reviews the evidence for it, and the second paper contrasts it with the traditional idea that schizophrenia involves impaired filtering.

The hyperfocusing hypothesis proposes that schizophrenia involves an abnormally narrow but intense focusing of processing resources. That is, people with schizophrenia are not impaired at focusing their attention; on the contrary, they tend to focus their attention more intensely and more narrowly compared to healthy control subjects. This hypothesis can explain findings from several different cognitive domains, including reductions in working memory capacity (because people with schizophrenia have difficulty dividing resources among multiple memory representations), deficits in experimental paradigms that involve spreading attention broadly (such as the Useful Field of View task), and abnormal capture of attention by irrelevant stimuli that share features with active representations. In addition to explaining many previous findings, the hyperfocusing hypothesis has also led to many new predictions that have been tested and verified. We also find that the degree of hyperfocusing is often correlated with the degree of impairment in measures of broad cognitive function, which are known to be related to long-term outcome.

When a psychiatric group exhibits impaired performance relative to a control group, there are usually many possible explanations (e.g., reduced motivation, impaired task comprehension). However, the hyperfocusing hypothesis proposes that people with schizophrenia focus more strongly than control subjects, which leads to the counterintuitive prediction that people with schizophrenia will exhibit supranormal focusing of processing resources under some conditions. And this is exactly what we have found in several experiments. For example, in both ERP and fMRI studies, we have found that delay-period activity is enhanced in people with schizophrenia relative to control subjects when only a single object is being maintained. This is an example of what we mean by a “more intense” focusing of processing resources. You might be concerned that people with schizophrenia exert greater effort to achieve the same memory performance, and this leads to greater delay-period activity. However, when we examine subgroups that are matched on behavioral measures of working memory capacity, we still find that people with schizophrenia exhibit enhanced activity relative to control subjects when a single item is being remembered.

Classically, schizophrenia has been thought to involve an impairment in selective attention, a “broken filter.” For example, one individual wrote the following in an online forum: “Ever since I started having problems due to schizophrenia, my senses have been thrown out of whack... I remember one day when I got caught in the rain. Each drop felt like an electric shock and I found it hard to move because of how intense and painful the feeling was.” How can we reconcile this evidence for increased distraction with the idea that schizophrenia involves hyperfocusing? The most likely rapprochement between the hyperfocusing hypothesis and the broken filter hypothesis is that schizophrenia also involves impaired executive control, so people with schizophrenia often point their “spotlight” of attention in the wrong direction. As a result, they may focus narrowly and intensely on inputs that would ordinarily be ignored (e.g., drops of rain), producing greater distractibility even though the filtering mechanism itself is operating very intensely.

New Paper: fMRI study of working memory capacity in schizophrenia

Hahn, B., Robinson, B. M., Leonard, C. J., Luck, S. J., & Gold, J. M. (2018). Posterior parietal cortex dysfunction is central to working memory storage and broad cognitive deficits in schizophrenia. The Journal of Neuroscience37, 8378–8387. https://doi.org/DOI: https://doi.org/10.1523/JNEUROSCI.0913-18.2018 https://doi.org/10.1523/JNEUROSCI.0913-18.2018.

In several behavioral studies using change detection/localization tasks, we have previously shown that people with schizophrenia (PSZ) exhibit large reductions in visual working memory storage capacity (Kmax). In one large study with 99 PSZ and 77 healthy control subjects (HCS), we found an effect size (Cohen's d) of 1.11, and the degree of Kmax reduction statistically accounted for approximately 40% of the reduction in overall cognitive ability exhibited by PSZ (as measured with the MATRICS Battery). Change detection tasks are much simpler than most working memory tasks, focus on storage rather than manipulation, and can be used across species. Thus, Kmax gives us a measure that is both neurobiologically tractable and strongly related to broad cognitive dysfunction.

In our most recent work, led by Dr. Britta Hahn at the Maryland Psychiatric Research Center, we used fMRI to examine the neuroanatomical substrates of reduced Kmax in PSZ. We took advantage of an approach pioneered by Todd and Marois (2004, Nature), in which a whole-brain analysis is used to find clusters of voxels where the BOLD signal is related to the amount of information actually stored in working memory (K). As shown in the figure below, we found the same areas of posterior parietal cortex (PPC) that were observed by Todd and Marois.

In the left PPC, however, the K-dependent modulation of activity was reduced in PSZ relative to HCS. As shown in the scatterplots, the BOLD signal in this region was strongly related to the number of items being held in working memory (K) in HCS, but the function was essentially flat in PSZ. However, the overall level of activation was just as great in PSZ as in HCS (the Y intercept). The reduced slope was driven mainly by an overactivation in PSZ relative to HCS when relatively little information was being stored in memory. Moreover, the slope was strongly correlated with overall cognitive ability (again measured using the MATRICS Battery), and the degree of slope reduction statistically accounted for over 40% of the reduction in broad cognitive ability in PSZ.

One particularly interesting aspect of these results is that they point to posterior parietal cortex as a potential source of cognitive dysfunction in schizophrenia, whereas most research and theory has focused on prefrontal cortex. Studies with healthy young adults have consistently identified PPC as a major player in working memory capacity and in the ability to divide attention, both of which are strongly impaired in PSZ. We hope that our study motivates more research to examine the potential contribution of the PPC to cognitive dysfunction in schizophrenia.

Hahn fMRI Change Detection.jpg

Electrophysiological Evidence for Spatial Hyperfocusing in Schizophrenia

Kreither, J., Lopez-Calderon, J., Leonard, C. J., Robinson, B. M., Ruffle, A., Hahn, B., Gold, J. M., & Luck, S. J. (2017). Electrophysiological Evidence for Spatial Hyperfocusing in SchizophreniaThe Journal of Neuroscience, 37, 3813-3823.

Double Oddball P3 Bar Graph.jpg

This paper from last spring describes new evidence for our hyperfocusing theory of cognitive dysfunction in schizophrenia.  Remarkably, we found that people with schizophrenia were actually better able to focus centrally and filter peripheral distractors than were control subjects. Under the right conditions, we even observed a (slightly) larger P3 wave in patients than in controls.