Mark Bowren, Jr., Ph.D.

The Iowa Brain Lesion and Neuromodulation Laboratory

Integrating Clinical Neuropsychology and Cognitive Neuroscience

The Iowa Brain Lesion and Neuromodulation Laboratory (BLNL) is a research team housed within the University of Iowa Carver College of Medicine. The goal of the BLNL is to advance our scientific understanding of brain mechanisms of human behavior and cognition. The BLNL works at the interface of cognitive neuroscience, clinical neuropsychology, neurology, neurosurgery, and psychiatry. We integrate behavioral science with a variety of neuroimaging tools to elucidate the structure of the mind through knowledge of the brain. The primary research techniques employed by the BLNL are lesion-deficit mapping and neuromodulation (e.g., direct electrical brain stimulation), both of which allow us to study how brain perturbations affect behavior and cognition. Thus, these methodologies enable rigorous, causal brain-behavior inferences that can be used to push the limits of the basic and clinical neurosciences.

Lesion-Behavior Mapping

The use of focal brain lesions to infer brain-behavior relationships has been central to cognitive neuroscience since at least the mid-19th century when Paul Broca described the anatomical correlates of expressive aphasia in his famous case study (Figure 1). Around the same time, George Harlow documented the childlike behavior of a formerly mature adult man, Phineas Gage (Figure 2), implicating the prefrontal lobe in personality. These case studies and others like them created foundational knowledge in the field of neuropsychology. Despite advances in functional neuroimaging, the lesion method (or "lesion-deficit mapping") remains critical to cognitive neuroscience and neuropsychology because it allows researchers and clinicians to infer the necessity of different brain structures for human cognition and behavior. In other words, the lesion method allows for "causal" inferences about brain-behavior relationships. This knowledge is essential to the clinical practice of neuropsychology (e.g., in helping to assess the brain regions generating seizure activity in patients with epilepsy). Today, lesion-deficit mapping can be performed using data from hundreds to thousands of patients thanks to advances in neuroimaging registration techniques, the formation of large-scale patient registries, and the creation of statistical pipelines specifically designed for the analysis of lesion data. Our lab uses lesion-behavior mapping to (1) test theories about the structure of cognitive abilities and behavior, and (2) develop methods for predicting cognitive deficits among patients with focal brain lesions (e.g., patients with stroke).

Figure 1. The post-mortem brain of Paul Broca's famous patient, "Tan." This case study was among the first examples of lesion-deficit inference in neuropsychology.

Figure 2. A rendering of the brain injury sustained by the famous patient, Phineas Gage. This case study helped scientists understand the brain systems involved in value-based decision-making.

Figure 3. Today, patient registries like the one at the University of Iowa allow for large-scale mapping of brain-behavior relationships. Pictured is a map of general cognitive ability derived from a cognitive model based on neuropsychological test data.

Lesion Network Mapping

In the mid-20th century, neurologist Norman Geschwind authored a landmark treatise concerning the localization of neurological syndromes to disconnections of long range white matter projections - the highways that allow neurons to communicate with one another. It is now widely recognized that complex thought and behavior likely arise from complex circuitry across distributed anatomical regions of the brain. Lesion network mapping is a statistical approach that integrates the lesion method with techniques from network neuroscience. Lesion-associated networks can be defined both by matter tracts (i.e., bundles of neuronal axons) that overlap with a lesion, and by the brain regions that show correlated blood flow to the affected region (Figure 4). Our lab uses lesion network mapping to (1) infer the shared and unique brain networks that are critical for different aspects of complex cognition and behavior, (2) generate new hypotheses about the structure of the mind, and (3) predict post-lesion deficits.

Figure 4. A schematic describing lesion network mapping analyses used to predict cognitive outcomes based on statistical models.

Intracranial Electrical Stimulation

Direct electrical stimulation of the brain has been a pillar of neurosurgery, and has been a powerful tool for cognitive neuroscience. Patients with drug-resistant epilepsy who are candidates for neurosurgery will often have electrodes placed into the brain to record brain activity related to seizures and identify brain regions necessary for important brain functions like language (which surgeons do their best to avoid to minimize deficits after surgery). However, most electrical stimulation mapping protocols do not involve identifying areas for important cognitive abilities. Moreover, electrical stimulation mapping of brain functions is typically limited to the brain's cortical surface despite recent lesion studies suggesting that the connections between cortical regions in the brain's "white matter" are more important for explaining cognitive deficits than the brain's cortical surface. Our lab seeks to understand the cognitive and neural mechanisms of important cognitive functions using direct electrical brain stimulation of white matter during specially designed cognitive tests. We also use diffusion weighted imaging-based tractography to visualize the connections affected by the stimulation. Altogether, our work in this area can allow us to learn more about the neuroscience of cognition, and could open the door to clinically useful techniques for mapping cognition to the brain for clinical outcome prediction.

Figure 5. Patients with drug-resistant epilepsy who are candidates for neurosurgical treatments will sometimes have electrodes implanted to help guide neurosurgery plans. Using diffusion weighted imaging (DWI), we can visualize the brain connections that intersect with the contact points of the electrodes. Brain connections in the figure are represented by green and purple colored lines. Electrode contacts are represented in the figure by red spheres). Using electrical stimulation, we seek to understand the brain pathways important for key cognitive functions so as to better predict cognitive outcomes after brain surgeries.