Our computational model of visual attention disruptions in schizophrenia

My latest modeling paper has been published in Computational Psychiatry.

Visual Attention Deficits in Schizophrenia Can Arise From Inhibitory Dysfunction in Thalamus or Cortex (Open Access!)

Here’s the abstract:

“Schizophrenia is associated with diverse cognitive deficits, including disorders of attention-related oculomotor behavior. At the structural level, schizophrenia is associated with abnormal inhibitory control in the circuit linking cortex and thalamus. We developed a spiking neural network model that demonstrates how dysfunctional inhibition can degrade attentive gaze control. Our model revealed that perturbations of two functionally distinct classes of cortical inhibitory neurons, or of the inhibitory thalamic reticular nucleus, disrupted processing vital for sustained attention to a stimulus, leading to distractibility. Because perturbation at each circuit node led to comparable but qualitatively distinct disruptions in attentive tracking or fixation, our findings support the search for new eye movement metrics that may index distinct underlying neural defects. Moreover, because the cortico-thalamic circuit is a common motif across sensory, association, and motor systems, the model and extensions can be broadly applied to study normal function and the neural bases of other cognitive deficits in schizophrenia.”

Here’s Figure 1, which shows the circuit we modeled.

How to navigate on Planet Brain

I was asked the following question on Quora: “How do you most easily memorize Brodmann’s areas?”. The question details added the following comment: “Brodmann area 7 is honestly where the numbering starts to seem really arbitrary.” Here’s how I responded:

Yup. The Brodmann numbering system for cortical areas is arbitrary. If you find a mnemonic, do let us know!

I’m a computational modeler working in an anatomy lab, so I confront the deficits in my anatomical knowledge on a daily basis! I can barely remember the handful of Brodmann areas relevant to my project, let alone the full list! I have a diagram of the areas taped up next to my monitor. 🙂

Neuroanatomists become familiar with the brain’s geography over years and years of “travel” through the brain. Think of it like this: what they’re doing is like navigating a city that doesn’t have a neat New York -style city block structure with sensibly numbered streets and avenues. Boston, where I live, is largely lacking in regularity, so one really has to use landmarks — like the Charles River, the Citgo sign, or the Prudential Center. The landmarks for neuroanatomists are sulci and gyri. Over time they learn the Brodmann area numbers. Only instead of a 2D city, neuroanatomists are mapping a 3D planet!


Over the years my lab — the Neural Systems Laboratory at Boston University — has developed a structural model that explains cortical areas and their interconnections in terms of cytoarchitectonic features. They don’t have a naming/addressing system, but at least they provide a way to make sense of the forest of areas!

Fig 1. Schematic representation of four broad cortical types. Agranular and dysgranular cortices are of the limbic type. Figure from [1].

The structural model [1,2] is based on the observation that the 6-layer nature of isocortex is not uniform, but varies systematically. The simplest parts of the cortex are the “limbic” cortices, which include posterior orbitofrontal and anterior cingulate cortices. Limbic cortices have around 4 distinct layers. The most differentiated parts of the cortex are the “eulaminate” cortices, which include primary sensory areas, and some (but not all!) parts of the prefrontal cortex, such as dorsolateral prefrontal cortex. Eulaminate cortices have 6 easily distinguished layers. [See Fig 1]. Interestingly, there is some evidence that the simplest cortices are phylogenetically oldest, and that the most differentiated are most recent.

Fig 2. Schematic representation of cortico-cortical projections. Figure from [2].

Every functional cortical hierarchy* consists of a spectrum of cortices from limbic to eulaminate areas. Areas which are similar tend to be more strongly connected to each other, with many layers linking to each other in a way that can be described as “columnar”, “lateral” or “symmetric”. Dissimilar areas are generally more weakly connected, and have an “asymmetric” laminar pattern of connections, in which projections from a less differentiated area to a more differentiated area originate in deep layers (5 and 6), and terminate in superficial layers (1,2 and 3). Projections from a more differentiated area to a less differentiated area have the opposite pattern: they originate in superficial layers (2 and 3), and terminate in deep layers (4,5 and 6). [See Fig 2.]

 For more on the details of the model, check out the references [1,2]. My boss, Helen Barbas, just submitted a short review about the structural model. When it is out I will append it to this answer.

To return to the city analogy, the structural model tells us that we can infer the (transportation/social/cultural?) links between pairs of neighborhoods based on what the two neighborhoods look like. If the structural model were true for cities, then neighborhoods that have similar houses and street layouts would be more closely linked that dissimilar neighborhoods. Similar neighborhoods would have one type of linkage (the “symmetric” type), whereas dissimilar neighborhoods would have another (the “asymmetric” type).

References

[1] Dombrowski SM, Hilgetag CC, Barbas H (2001) Quantitative architecture distinguishes prefrontal cortical systems in the rhesus monkey. Cereb Cortex 11: 975-988.

[2] Barbas H, Rempel-Clower N (1997) Cortical structure predicts the pattern of corticocortical connections. Cereb Cortex 7: 635-646.

Notes

* Heterarchy might be a better description than hierarchy.

Here’s a link to the Quora answer: How do you most easily memorize Brodmann’s areas?