MedicalResearch.com Interview with:
Kay Jann, PhD, Department of Neurology
Danny JJ Wang, Prof., Department of Neurology
Laboratory of Functional MRI Technology
Ahmanson-Lovelace Brain Mapping Center
Department of Neurology
University of California Los Angeles
Medical Research: What is the background for this study? What are the main findings?
Response: The brain controls most of our behavior and thus changes in how brain areas function and communicate with each other can alter this behavior and lead to impairments associated with mental disorders. Higher cognitive functions are controlled by brain areas that form complex interconnected networks and alterations in these networks can lead to cognitive impairments. In autism, one such network is the so called default mode network. This network controls self-referential thoughts, reasoning past and future and is involved in understanding mental states of others (i.e. Theory of Mind).
Functional MRI based functional connectivity is a research tool to understand the interrelations between brain areas and how separate, distributed areas can be organized into brain networks that serve specific cognitive functions. In autism, local hyperconnectivity along with hypoconnectivity in long range connections between anterior and posterior cingulate cortices has been discussed to be one of the physiological underpinnings of the behavioral symptoms in social interaction and cognition observed in austism. It is hypothesized to be due to a developmental delay and disbalance of the balance between neuronal excitation/inhibition in brain areas that lead to oversynchronized strong short-range (local) networks while long-range connections that develop later in neurodevelopment are less well established.
In our study, we used a non-invasive MRI technique called arterial spin labeling (ASL) perfusion MRI for the first time in autism research. Similarly to Positron Emission Tomography (PET) this technique allows measuring cerebral blood flow (CBF), however without the need to inject radioactive tracers. ASL MRI uses magnetically labeled blood water as an endogenous tracer to quantify CBF. Accordingly, our approach enabled us to combine information about how brain areas are functionally connected, as well as their associated metabolic energy consumption in autism spectrum disorder.
We found that in typically developing children, the known relation between how strongly an area is connected to other areas in a brain network, the more energy it requires holds. In children with autism spectrum disorder this relation, however, was disrupted in a major brain area (the dorsal anterior cingulate cortex) that is relevant to social interactions and in Theory of Mind. Both are cognitive processes that are to some extent impaired in persons with autism spectrum disorders.
Medical Research: What should clinicians and patients take away from your report?
Response: Using ASL perfusion imaging we were able to estimate a quantitative measure for energy demand and neuronal activity. This quantitative information on CBF is not available by conventional functional MRI studies but represents another critical marker for brain functionality.
Having this information in addition to the connectivity results we were able to show a relation between connectivity and energy demand in the default mode network of children similar to what we previously observed in adults. Moreover, we identified an area in children with autism, that showed reduced CBF (hypoperfusion) and increased local connectivity but reduced long-range connections: the dorsal anterior cingulate cortex. Surprisingly, the relation between connectivity and perfusion measures was disrupted in children with autism, indicating a change in the energy demand in critical parts of brain networks related to the symptomatology of autism. This altered energy consumption might indeed indicate a change in the ecitatory/inhibitory balance of the networks as mentioned above.
The findings of this study – the first to jointly assess resting CBF and functional connectivity in Autism spectrum disorder – highlight new avenues for identifying novel imaging markers of autism (or other disorders) symptomatology that combine network connectivity and its energetic cost.
Medical Research: What recommendations do you have for future research as a result of this study?
Response: Efficient communication and integration of information between brain regions play key roles in healthy brain function, hence alterations in this communication and/or their energy supply may lead to cognitive and behavioral problems. As such, communication and energy demand are not independent characteristics of brain functionality but tightly coupled.
The applied technique helps to better understand the relation between functional organization of the brain and its accompanying energy demand. Specifically in neurocognitive or neuropsychiatric disorders these crucial properties of brain functionality are often found to be altered. So far however, these two related characteristics are investigated separately from each other.
Understanding the physiological changes associated with a disorder and observed behavioral and cognitive impairments could help to develop novel treatment approaches and imaging methods could also be used to monitor treatment efficacy. Hence, a deepened understanding of how these two critical components of brain functionality are coupled and respectively altered in specific disorders will lead to a better characterization of patients and identify subgroups that could benefit from tailored treatments. In other disorders, namely schizophrenia, this approach has already led to novel insight and alternative treatment options.
Kay Jann, Leanna M. Hernandez, Devora Beck-Pancer, Rosemary McCarron, Robert X. Smith, Mirella Dapretto, Danny J. J. Wang. Altered resting perfusion and functional connectivity of default mode network in youth with autism spectrum disorder. Brain and Behavior, 2015; 5 (9) DOI: 1002/brb3.358
Kay Jann, PhD, Prof. Danny JJ Wang (2015). Non-Invasive MRI Demonstrates Reduced Brain Connectivity in Autism Spectrum Disorder