Project Description Narrative:
Relationships between brain anatomy and human behavior, especially in patients with brain cancer, need to be better understood. According to the American Cancer Society, Wisconsin is in the 72nd and 63rd percentiles in the U.S. for incidence and death due to brain and central nervous system cancer, respectively. This suggests that brain cancer is disproportionally problematic in Wisconsin, but healthcare providers here treat it relatively successfully. Many patients with brain tumors present with motor weakness and have a good post-operative recovery, which is important for both quality of life and survival. However, not everyone recovers function, and how brain cancer creates problems with movement and activities of daily living is poorly understood. Moreover, long-term survival in brain cancer is inversely associated with poor motor function, inability to work, and other financial burdens. Therefore, the need to maximize motor functional outcomes for patients with brain tumors is clear. To do so, however, requires a better understanding of the mechanisms underlying tumor-related neurological dysfunction and recovery, which the researchers in this project seek to directly explore.
This project aims to establish initial evidence for a movement-based “disconnectome-reconnectome” model of neurological dysfunction and recovery, potentially redefining the understanding of neuromotor injury and opening the door for an entirely new avenue of neurorehabilitation for patients with brain tumors in Wisconsin. The researchers expect that recovery of functional connectivity of non-traditional motor networks will correlate with recovery of grip strength (basic motor function) and force-matching (complex motor function) abilities independently of primary motor pathway integrity after surgery. In future work, they will stratify the connectomes of “recoverers” and “non-recoverers” to generate more educated hypotheses about why some recover while others do not. From there, they will be poised to propose novel and targeted neuromodulation and rehabilitation paradigms designed to facilitate therapeutic brain-to-brain reconnections. Collectively, the field of neuroscience has been shifting away from the idea that the brain functions in an assortment of independent modules (i.e., localizationism) toward the idea that the brain functions through various interconnected, semi-redundant, hierarchical networks (i.e., connectomics). Within the newer model, mechanisms of function, dysfunction, and recovery are now being mapped to connections, disconnections, and reconnections, respectively, instead of the previously allocated fixed locations in the brain. Here we refer to this concept as a “disconnectome-reconnectome” model of disfunction and recovery. In the motor system, basic motor functions are classically localized to the primary motor cortices (M1) and their descending corticospinal tracts. This project seeks to challenge this convention. Evidence is building that non-traditional, large-scale network connectivity also likely has an important contribution to motor function. Some important networks for this include the dorsal attention network (DAN) responsible for integration of goal-directed, spatial attention to tasks and the visual network responsible for perceiving visual cues. Together, these networks are involved in goal-directed action, scaling motor output, and spatial perception and processing, therefore, they may be necessary to proper motor recovery in patients with brain tumors.
To directly test this theory, ten participants with focal brain tumors will undergo hand motor testing to assess strength, visuomotor, and somatosensory-motor integration at presentation (i.e., preoperatively) and after recovery (i.e., three months post-resection). Hand strength (i.e., force generation) is a basic motor property classically thought to rely heavily on the primary motor system. More complex motor behaviors, such as matching a prescribed force output, require real-time integration of attention, memory, visual, and sensory systems. Here we will correlate basic and complex motor functions to the connectivity of relevant MRI-based functional brain networks pre- and post-treatment in each participant. Strengths of correlations between relevant network connectivity and task performance will be interpreted as preliminary evidence of potentially causal relationships (pre- to post-surgery increased connectivity = increased function) to be further refined in future larger studies.
In sum, this work will establish initial evidence for a movement-based “disconnectome-reconnectome” model of neurological dysfunction and recovery, potentially redefining our understanding of neuromotor injury and opening the door for an entirely new avenue of neurorehabilitation for patients with brain tumors in Wisconsin. We expect that recovery of functional connectivity of non-traditional motor networks will correlate with recovery of grip strength (basic motor function) and force-matching (complex motor function) abilities independently of primary motor pathway integrity after surgery. Future work will stratify the connectomes of “recoverers” and “non-recoverers” to generate more educated hypotheses about why some recover while others do not. From there, the investigative team will be poised to propose novel and targeted neuromodulation and rehabilitation paradigms designed to facilitate therapeutic brain-to-brain reconnections.