This is a re-application for an NIMH Mentored Patient-Oriented Research Career Development Award (K-23), entitled """"""""Cerebellar Structure and Function in Adult ADHD."""""""" Adult attention deficit hyperactivity disorder (ADHD) is associated with functional impairments in multiple life domains, high rates of psychiatric co-morbidity, and neurocognitive dysfunction. Though most ADHD research has focused on examining frontal-striatal dysfunction, the discovery of cerebellar abnormalities in both structural and functional neuroimaging studies provides compelling evidence that the cerebellum may play a critical role in the pathophysiology of ADHD. Nonetheless, the nature of this involvement and the degree to which it influences ADHD deficits, such as in motor coordination, temporal processing, and working memory, are poorly understood. Through the proposed studies the candidate plans to examine the structural and functional integrity of the cerebellum in adult ADHD in order to elucidate its role in the symptomatology of this highly understudied disorder. The candidate proposes to use a state-of-the-art parcellation technique to conduct a more detailed structural analysis of the cerebellum than has been previously possible. She will also conduct an ataxia assessment along with a series of behavioral and functional MRI (fMRI) experiments which will test the hypothesis that abnormal cerebellar functioning contributes to ADHD deficits via timing and temporal processing irregularities. Finger tapping and duration discrimination as well as working memory tasks will serve as probes of timing irregularities in the ADHD cerebellum. It is the hope that this work will contribute not only to our understanding of adult ADHD, but eventually to childhood ADHD, and lead to improved recognition, response, and treatment of ADHD across the lifespan. This training program builds on the candidate's strengths in neuropsychology and psychopathology, and will allow her to take advantage of the extraordinary resources and mentors she has available to her both within and outside the MGH community. This program of research will provide the candidate with advanced training in: cerebellar anatomy, circuitry, and neurobiology; structural and functional analysis of the cerebellum in normal and psychiatric populations; neurological assessment; the cognitive neuroscience of timing, temporal processing and working memory; advanced MRI acquisition and analysis techniques (such as cortical inflation and flat mapping, cerebellar parcellation), and developmental neuropsychology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23MH071535-01A1
Application #
6924081
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Wynne, Debra K
Project Start
2005-07-01
Project End
2010-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
1
Fiscal Year
2005
Total Cost
$156,792
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Makris, Nikos; Liang, Lichen; Biederman, Joseph et al. (2015) Toward Defining the Neural Substrates of ADHD: A Controlled Structural MRI Study in Medication-Naïve Adults. J Atten Disord 19:944-53
Stoodley, Catherine J; Valera, Eve M; Schmahmann, Jeremy D (2012) Functional topography of the cerebellum for motor and cognitive tasks: an fMRI study. Neuroimage 59:1560-70
Brown, Ariel; Biederman, Joseph; Valera, Eve et al. (2012) Working memory network alterations and associated symptoms in adults with ADHD and Bipolar Disorder. J Psychiatr Res 46:476-83
Seidman, Larry J; Biederman, Joseph; Liang, Lichen et al. (2011) Gray matter alterations in adults with attention-deficit/hyperactivity disorder identified by voxel based morphometry. Biol Psychiatry 69:857-66
Brown, Ariel Beth; Biederman, Joseph; Valera, Eve et al. (2011) Relationship of DAT1 and adult ADHD to task-positive and task-negative working memory networks. Psychiatry Res 193:7-16
Valera, Eve M; Spencer, Rebecca M C; Zeffiro, Thomas A et al. (2010) Neural substrates of impaired sensorimotor timing in adult attention-deficit/hyperactivity disorder. Biol Psychiatry 68:359-67
Valera, Eve M; Brown, Ariel; Biederman, Joseph et al. (2010) Sex differences in the functional neuroanatomy of working memory in adults with ADHD. Am J Psychiatry 167:86-94
Brown, Ariel B; Biederman, Joseph; Valera, Eve M et al. (2010) Effect of dopamine transporter gene (SLC6A3) variation on dorsal anterior cingulate function in attention-deficit/hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet 153B:365-375
Stoodley, Catherine J; Valera, Eve M; Schmahmann, Jeremy D (2010) An fMRI study of intra-individual functional topography in the human cerebellum. Behav Neurol 23:65-79
Valera, Eve M; Faraone, Stephen V; Murray, Kate E et al. (2007) Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder. Biol Psychiatry 61:1361-9