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The Journal of Neuroscience, June 7, 2006, 26(23):6354-6363; doi:10.1523/JNEUROSCI.0549-06.2006

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Neurobiology of Disease
Medial Versus Lateral Frontal Lobe Contributions to Voluntary Saccade Control as Revealed by the Study of Patients with Frontal Lobe Degeneration

Adam L. Boxer,¹ Siobhan Garbutt,² Katherine P. Rankin,¹ Joanna Hellmuth,¹ John Neuhaus,³ Bruce L. Miller,¹ and Stephen G. Lisberger^2,4

¹Department of Neurology, Memory and Aging Center, ²Department of Physiology, Keck Center for Integrative Neuroscience, ³Department of Epidemiology and Biostatistics, and ⁴Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California 94143-1207

Correspondence should be addressed to Adam L. Boxer, Memory and Aging Center, Department of Neurology, University of California, San Francisco, Box 1207, San Francisco, CA 94143-1207. Email: aboxer{at}memory.ucsf.edu

Deficits in the ability to suppress automatic behaviors lead to impaired decision making, aberrant motor behavior, and impaired social function in humans with frontal lobe neurodegeneration. We have studied patients with different patterns of frontal lobe dysfunction resulting from frontotemporal lobar degeneration or Alzheimer's disease, investigating their ability to perform visually guided saccades and smooth pursuit eye movements and to suppress visually guided saccades on the antisaccade task. Patients with clinical syndromes associated with dorsal frontal lobe damage had normal visually guided saccades but were impaired relative to other patients and control subjects in smooth pursuit eye movements and on the antisaccade task. The percentage of correct antisaccade responses was correlated with neuropsychological measures of frontal lobe function and with estimates of frontal lobe gray matter volume based on analyses of structural magnetic resonance images. After controlling for age, gender, cognitive status, and potential interactions between disease group and oculomotor function, an unbiased voxel-based morphometric analysis identified the volume of a segment of the right frontal eye field (FEF) as positively correlated with antisaccade performance (less volume equaled lower percentage of correct responses) but not with either pursuit performance or antisaccade or visually guided saccade latency or gain. In contrast, the volume of the presupplementary motor area (pre-SMA) and a portion of the supplementary eye fields correlated with antisaccade latency (less volume equaled shorter latency) but not with the percentage of correct responses. These results suggest that integrity of the presupplementary motion area/supplementary eye fields is critical for supervisory processes that slow the onset of saccades, facilitating voluntary saccade targeting decisions that rely on the FEF.

Key words: antisaccade; smooth pursuit; frontotemporal lobar degeneration; presupplementary motor area; supplementary eye field; frontal eye field; brain volume

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Received Dec. 9, 2005; revised April 28, 2006; accepted May 9, 2006.

Correspondence should be addressed to Adam L. Boxer, Memory and Aging Center, Department of Neurology, University of California, San Francisco, Box 1207, San Francisco, CA 94143-1207. Email: aboxer{at}memory.ucsf.edu

This article has been cited by other articles:

				A. Yoshida and M. Tanaka Enhanced Modulation of Neuronal Activity during Antisaccades in the Primate Globus Pallidus Cereb Cortex, January 1, 2009; 19(1): 206 - 217. [Abstract] [Full Text] [PDF]

				S. Garbutt, A. Matlin, J. Hellmuth, A. K. Schenk, J. K. Johnson, H. Rosen, D. Dean, J. Kramer, J. Neuhaus, B. L. Miller, et al. Oculomotor function in frontotemporal lobar degeneration, related disorders and Alzheimer's disease Brain, May 1, 2008; 131(5): 1268 - 1281. [Abstract] [Full Text] [PDF]

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