There is currently a great interest in understanding attentional processing at the cellular, neurosystems, and behavioral levels. Data from cognitive, electrophysiological, metabolic, developmental, and brain-lesion studies converge to suggest that in normal processing, selective attention operations require coordinated interaction among frontal, parietal, brainstem, and thalamic systems. Although much is understood about systems involved in sustaining a single focus of attention, much less is known about the neural operations involved in the rapid changing of attentional maps during shifts in the focus of attention.
Until recently, models of the neural systems involved in attention did not include a role for the cerebellum. However, based on anatomical connections and recent physiological data, Courchesne and colleagues proposed that neocerebellar lesions may lead to dysfunction in attentional processes. In our laboratory, we are testing this new model by studying patients with focal cerebellar lesions and patients with autism, a disorder involving Purkinje neuron loss restricted to the neocerebellum. Neuroanatomical characteristics of patients are obtained by volumetric analyses of abnormal and spared anatomical regions. Neurophysiological activity is recorded while patients and controls perform tasks testing attentional capacity.
Results show that neocerebellar damage impairs the ability to rapidly and accurately change attentional maps during shifts of attention between auditory and visual information as well as between perceptual domains (locations, color, form) within the visual modality.
These findings have led to new concepts about the role of the human neocerebellum in mental as well as motor operations, and to a new theory of the neural basis for infantile autism, a developmental disorder characterized by severe impairment in joint social attention. Ongoing structural and functional neuroimaging, neurophysiological, and behavioral studies compare and contrast the roles of the neocerebellum and other neural systems in the dynamic control of selective attention.
For instance, we are currently employing functional magnetic resonance imaging (fMRI) to confirm a role for the normal human cerebellum in attention operations, and to test new concepts of cerebellar function that go beyond a traditional motor view. The other major area of research in this lab is the neurodevelop- mental disorder of autism. More than 200 autistic patients and non- autistic controls have entered our ongoing research program. Detailed neurological and neuropsychological testing is performed on these patients and structural magnetic resonance (MR) images are gathered as part of our longitudinal study. Using this information, we have demonstrated hypoplasia of the cerebellum in the majority of autistic patients and a loss of parietal lobe tissue in a subset of autistic patients. These findings correlate with deficits in certain attentional abilities believed to rely on parietal lobe function and have supported a possible role of the cerebellum in attentional function as described above. Ongoing research examines the neuroanatomy of other brain regions which have been implicated in autism (frontal lobes, basal ganglia, etc.) using structural MR imaging. We are also using neurophysiological techniques (ERP) and fMRI techniques to assess cognitive function in autism. We are also beginning an investigation into the genetics of the disorder.
Courchesne E, Mouton PR, Calhoun ME, Semendeferi K, Ahrens-Barbeau C, Hallet MJ, Barnes CC, Pierce K. Neuron number and size in prefrontal cortex of children with autism. JAMA. 2011 Nov 9;306(18):2001-10. PubMed PMID: 22068992.
Chow ML, Li HR, Winn ME, April C, Barnes CC, Wynshaw-Boris A, Fan JB, Fu XD, Courchesne E, Schork NJ. Genome-wide expression assay comparison across frozen and fixed postmortem brain tissue samples. BMC Genomics. 2011 Sep 10;12:449. PubMed PMID: 21906392; PubMed Central PMCID: PMC3179967.
Pierce, K., Carter, C., Weinfeld, M., Desmond, J., Hazin, R., Bjork, R., Gallagher, N. Detecting, studying, and treating autism early: the one-year well-baby check-up approach. Journal of Pediatrics, 158:5, 2011.
Pierce, K., Conant, D., Hazin, R., Desmond, J., & Stoner, R. A preference for geometric patterns early in life as a risk factor for autism. Archives of General Psychiatry. 68(1):101-9, 2011.
Courchesne, E., Campbell, K., Solso, S. Brain growth across the life span in autism: Age-specific changes in anatomical pathology. Brain Research, 1380:138-45, 2011
Delahanty, R.J., Kang, J.Q., Brune, C.W., Kistner, E.O., Courchesne, E., Cox, N.J., Cook, E.H. Jr, Macdonald, R.L., Sutcliffe, J.S. Maternal transmission of a rare GABRB3 signal peptide variant is associated with autism. Molecular Psychiatry. 16(1):86-96, 2011
Pierce, K. Early functional brain development in autism and the promise of sleep fMRI. Brain Research, 1380:162-74, 2011
Morgan, J.T., Chana, G., Pardo, C.A., Achim, C., Semendeferi, K., Buckwalter, J., Courchesne, E., Everall, I.P. Microglial Activation and Increased Microglial Density Observed in the Dorsolateral Prefrontal Cortex in Autism. Biological Psychiatry, 15;68(4):368-376, 2010.
Schumann, C.M., Bloss, C.S., Barnes, C.C., Wideman, G.M., Carper, R.A., Akshoomoff, N., Pierce, K., Hagler, D., Schork, N., Lord, C., Courchesne, E. Longitudinal magnetic resonance imaging study of cortical development through early childhood in autism. Journal of Neuroscience, 30(12):4419-27, 2010.