Dosenbach Lab | Research

The human brain is the most complex thing, and it matters to all of us. There’s nothing better to research.

To properly study brain organization and function in humans, we must overcome a series of exciting challenges. Hence, we have created a multi-pronged plan of attack and are coming at this fascinating problem from several different angles.

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Precision functional mapping (PFM) of individual human brains

Individual brains differ in the details of their network organization. Therefore, we have moved away from averaging neuroimaging data across groups of people. Instead, we collect larger amounts of high-quality functional and structural MRI data for each individual. This allows us to generate precise individual-specific functional network maps of human brains. The Midnight Scan Club project collected many hours of high quality, multi-modal MRI data in 10 young adults (24-34 yo; 5F). Even this small, homogenous sample revealed common variants in the brain’s global network organization. This PFM approach also revealed the previously unrecognized Somato-Cognitive Action Network (SCAN), which forced a revision of Penfield’s classical motor homunculus.

Brain-wide association studies (BWAS)

BWAS are on the other end of the neuroimaging study design spectrum from precision functional mapping. Instead of repeatedly sampling the same study participants, they depend on very large consortium data sets with n >1,000. We introduced the term and formally defined them as “studies of associations between common inter-individual variability in human brain structure/function and cognition or psychiatric symptomatology. While individual-specific brain maps are more immediately applicable to the medical practice, BWAS have the potential for population-level generalizability. We are using BWAS to investigate epidemiological brain questions, using all the largest available consortium data sets.

Medication effects on the brain: Precision Imaging Drug Trials

The basic repeated sampling PFM approach lends itself exceptionally well to studying the effects of drugs on the human brain, both acutely and longer term. Precision Imaging Drug Trials (PIDT) have enabled us to better understand the mechanisms of psychoactive substances such as psychedelics and stimulants at the level of individuals. PIDTs are rapid and cost effective means for developing imaging biomarkers for novel drugs and better understanding drug mechanisms in humans.

Behavioral plasticity interventions

Identifying and tracking plastic brain changes in single individuals requires powerful interventions. Therefore, we have been studying Constraint-Induced Movement Therapy (CIMT), which requires restricting the more mobile limb with a cast, in children with chronic hemiparesis. We adapted this treatment for the in-depth study of limb disuse and accompanying brain changes in healthy young adults. This approach led to the discovery of disuse-associated spontaneous activity pulses, that we are continuing to investigate, including in Parkinson’s Disease.

Perinatal stroke as a model of successful neuroplasticity

Perinatal stroke (22 wks gest. - 28 days) occurs in > 1/3,000 live births. Some perinatal stroke survivors have no discernable deficits and many have only minimal impairments. Thus, perinatal stroke can represent a best-case recovery scenario that reveals the brain’s full potential for successful use-driven neuroplasticity. Using individual-specific precision functional mapping, we are learning how the brains of individual perinatal stroke survivors can function so remarkably well despite structural damage. This information is critically important for developing therapies that can drive the brains of all brain injury survivors towards a similarly efficient functional architecture, independent of age.

Real-time methods for improving MRI quality

A challenge common to all MRI is its vulnerability to head motion-associated distortions. In response, we developed the Framewise Integrated Real-Time MRI Monitoring (FIRMM) software suite for real-time quality control and biofeedback-based motion-reduction. Together with Turing Medical (turingmedical.com), which has licensed the technology, we continue working on further improvements to FIRMM, as well as expanding the approach to drowsiness monitoring.

Deep phenotyping

To understand how differences in functional brain organization relate to behavior and to learn how brain structures and abilities change with behavior, we must do a better job tracking and measuring real-world behaviors. Questionnaires are notoriously unreliable and laboratory-based assessments are unrealistic, therefore we have turned to wearable biosensors. We have generated a database of normative activity, as measured by bilateral upper extremity accelerometry, in children from birth until 18 years of age. In addition to standard neuropsychological tests and the NIH Toolbox, we are adding accelerometry whenever possible, to garner information about sleep and activity levels.

The list of research areas above is far from exhaustive since our rate limiting factor is people-power, not ideas. The general tenor of all the ideas/projects is that we are looking for better and more data, both for individual-specific and population-level approaches. We’re interested in manipulations that will help us understand plasticity and we like going after difficult to obtain human data. We’re also interested in hardware and software tool development that will improve MRI data quality and bring us closer towards using functional MRI as a diagnostic tool in the hospital.