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New research led by medical student shows ‘exquisitely’ organized network interactions in adolescent brain underpin attention processing

Discovery may inform understanding of clinical neuropsychiatric syndromes

May 26, 2016

Dynamic brain network interactions in the healthy adolescent brain are remarkably more sophisticated and sensitive to attention demands than previously demonstrated. That is one takeaway from a seminal publication led by Pranav Jagtap, a fourth-year medical student in the Wayne State University School of Medicine’s Department of Psychiatry and Behavioral Neurosciences. His paper on “Effective Connectivity of Ascending and Descending Frontal-thalamic Pathways During Sustained Attention: Complex Brain Network Interactions in Adolescence,” is slated for the June issue of the journal Human Brain Mapping and demonstrates “the beautiful and exquisite functional optimization of the adolescent brain,” said Vaibhav Diwadkar, Ph.D., associate professor and senior author on the study.

In the study, the investigative team collected functional magnetic resonance imaging, or fMRI, signals in a group of healthy adolescents (11 to 19 years old) during a sustained attention task. Sustained attention is the ability to maintain focus or remain vigilant for long periods of time. Impaired attention often emerges in adolescence, and is observed across multiple psychiatric illnesses, most obviously in attention deficit hyperactivity disorder. Understanding attention mechanisms in the healthy adolescent brain is of particularly high clinical relevance. The team’s focus on this behavioral domain reflects a search for discovering brain network mechanisms, that if identified might inform understanding of many of these clinical syndromes.

“Sustained attention and vigilance are foundational elements of behavioral function, and a pre-requisite for many more complex behaviors. Moreover, the demands of sustained attention vary, sometimes being very intense and sometimes being very light,” said Dr. Diwadkar said, who co-directs the department’s Brain Imaging Research Division.

“Of course, the brain can implement sophisticated behaviors like sustained attention, largely because it is itself a complex network. In the past, imaging studies have typically focused on characterizing isolated activity of brain regions. Yet, it is now widely accepted that it is only through sophisticated discovery of network connectivity between regions that we can understand mechanisms of complex behavior. Discovering this connectivity is a non-trivial problem; yet this process of discovery is crucial if we are to understand how the brain ‘works.’ This was the major thrust of this work,” he added.

The sustained attention task used in the study varied attention demand and induced dynamics in fMRI signals across multiple brain regions. Changes in the fMRI signal contain information about the brain’s network interactions that can be recovered using complex analytic methods. The team focused on interactions between the prefrontal cortex and the thalamus, two brain regions previously shown to have important roles in sub-serving attention. The thalamus has been called the ‘gateway’ to the cortex, and signals from the thalamus are fed upward to cortical regions such as the prefrontal cortex for more elaborate processing. “However, the cortex can modify how the thalamus functions through descending inputs. Thus there is presumed to be a sophisticated interplay between these ascending (thalamus to prefrontal cortex) and descending (prefrontal cortex to thalamus) pathways,” Dr. Diwadkar said.

To understand network dynamics between these regions, the team quantitatively modeled fMRI signals using complex effective connectivity analyses that estimate causal interactions between brain regions. “These methods are considered one of the highest standards for network analyses of fMRI data,” Dr. Diwadkar said.

The team showed that the effective connectivity of the ascending thalamus to prefrontal pathway is not differentially affected by the varying demands of the sustained attention task, reaffirming that the ascending pathway is a gateway that appropriately sends information upward without filtering. However, the effective connectivity of the descending prefrontal to thalamus pathway showed increased connectivity when attention demand is high.

“Remarkably, even in adolescence, network interactions from the cortex to the thalamus are highly sensitive to the difficulty of the task, dynamically increasing connectivity in the face of increased attention demand. That we observed this in the adolescent brain speaks to the complexity with which the brain dynamically implements behavior, and demonstrates the beautiful organization of network interactions. This is a highly elegant revelation,” he said.

The team is extending the analytic approaches in support of discovering brain network dysfunction in adolescent and adult clinical syndromes, including obsessive-compulsive disorder.

”Understanding how the brain implements behavior is a remarkable challenge, and many of the problems in understanding neuropsychiatric syndromes are linked to solving this challenge. Our efforts in the Brain Imaging Research Division are directed at applying sophisticated analytic approaches toward unraveling many of these difficult questions. We are hopeful that our explorations will illuminate some understanding of mechanisms of typical brain network interactions, and how impairments in these contribute to the emergence of psychiatric syndromes,” Dr. Diwadkar said.

The research was supported by grants from the National Institute of Mental Health (MH68680 and MH59299), the National Alliance for Research on Schizophrenia and Depression, the Children’s Research Center of Michigan, the Children’s Hospital of Michigan Foundation, the Prechter Pediatric Bipolar Program World Heritage Foundation, the Cohen Neuroscience Endowment and the Lycaki-Young Fund from the State of Michigan. Additional support was provided by a Summer Medical Student Research Fellowship given by the WSU School of Medicine to Jagtap, and a Career Development Chair and Charles H. Gershenson Distinguished Faculty Fellowship to Dr. Diwadkar from the WSU Office of the President.

About Wayne State University, www.wayne.edu 

Wayne State University is a premier urban research institution offering more than 380 academic programs through 13 schools and colleges to nearly 27,000 students. Its School of Medicine educates more than 1,000 medical students in Midtown Detroit. In addition to undergraduate medical education, the school offers master’s degree, Ph.D. and M.D.-Ph.D. programs in 14 areas of basic science to about 400 students annually.