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1.  Saccade abnormalities in autopsy-confirmed frontotemporal lobar degeneration and Alzheimer’s disease 
Archives of neurology  2012;69(4):509-517.
Objective
Deficits in the generation and control of saccades have been described in clinically-defined frontotemporal dementia (FTD) and Alzheimer’s disease (AD). Because clinical FTD syndromes can correspond to a number of different underlying neuropathologic FTD and non-FTD diagnoses, we sought to determine the saccade abnormalities associated with autopsy-defined cases of FTLD and AD.
Participants and design
An infrared eye tracker was used to record visually guided saccades to ten degree targets and antisaccades in 28 autopsy-confirmed FTD and 10 AD subjects, an average of 35.6 ± 10 months prior to death and 27 age-matched normal controls (NC). 12 FTD subjects had FTLD-TDP pathology, 15 had FTLD-tau pathology and one showed FTLD-FUS pathology. Receiver operating curve (ROC) statistics were used to determine diagnostic value of oculomotor variables. Neuroanatomical correlates of oculomotor abnormalities were investigated using voxel-based morphometry (VBM).
Results
All FTD and AD subjects were impaired relative to NC on the antisaccade task. However, only FTLD-tau and AD cases displayed reflexive visually-guided saccade abnormalities. AD cases displayed prominent increases in horizontal saccade latency that differentiated them from FTD cases. Impairments in velocity and gain were most severe in individuals with Progressive Supranuclear Palsy (PSP) but were also present in other tauopathies. Vertical and horizontal saccade velocity and gain were able to differentiate PSP cases from other patients. Vertical saccade velocity was strongly correlated with dorsal midbrain volume.
Conclusion
Decreased visually-guided saccade velocity and gain are suggestive of underlying tau pathology in FTD, with vertical saccade abnormalities most diagnostic of PSP.
doi:10.1001/archneurol.2011.1021
PMCID: PMC3423186  PMID: 22491196
Frontotemporal Dementia; Corticobasal Degeneration; Progressive Supranuclear Palsy; Ocular Motility
2.  Directional Cuing of Target Choice in Human Smooth Pursuit Eye Movements 
Perceptual attention and target choice for movement have many features in common. In particular, both generally are based on selection of a particular location in space. To ask whether motor control, like attention, also can exhibit target choice based on nonspatial features of the stimulus, we assessed the initiation of smooth pursuit eye movements when two targets move in different directions after human subjects have been cued which direction or color to track. The direction cue consisted of a patch of dots undergoing either 0% coherent motion or 50% coherent motion in the direction of motion of one of the subsequent targets. After a delay, the fixation spot was extinguished and two spots moved across the same small region of the visual field, one in the cued direction (“target”) and one in an orthogonal direction (“distracter”). After the 0% coherent cue, pursuit was approximately the vector average of responses to the two motions presented singly. After the 50% coherent cue, the initial pursuit response was biased strongly toward the target that moved in the cued direction. The impact of the cued direction persisted over delays of up to 1000 ms. Other cues about the direction of upcoming target motion biased the response similarly. Cues about target color also biased pursuit in the direction of motion of the cued target but were considerably less effective than cues indicating the direction of target motion. We conclude that target choice for movement, like perceptual attention, can be based on the features of the chosen target and not only its location in space.
doi:10.1523/JNEUROSCI.4071-06.2006
PMCID: PMC2567914  PMID: 17135410
motor planning; delay period; oculomotor; vector averaging; attention; motion processing
3.  Medial Versus Lateral Frontal Lobe Contributions to Voluntary Saccade Control as Revealed by the Study of Patients with Frontal Lobe Degeneration 
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.
doi:10.1523/JNEUROSCI.0549-06.2006
PMCID: PMC2551317  PMID: 16763044
antisaccade; smooth pursuit; frontotemporal lobar degeneration; presupplementary motor area; supplementary eye field; frontal eye field; brain volume
4.  Oculomotor function in frontotemporal lobar degeneration, related disorders and Alzheimer's disease 
Brain  2008;131(5):1268-1281.
Frontotemporal lobar degeneration (FTLD) often overlaps clinically with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), both of which have prominent eye movement abnormalities. To investigate the ability of oculomotor performance to differentiate between FTLD, Alzheimer's disease, CBS and PSP, saccades and smooth pursuit were measured in three FTLD subtypes, including 24 individuals with frontotemporal dementia (FTD), 19 with semantic dementia (SD) and six with progressive non-fluent aphasia (PA), as compared to 28 individuals with Alzheimer's disease, 15 with CBS, 10 with PSP and 27 control subjects. Different combinations of oculomotor abnormalities were identified in all clinical syndromes except for SD, which had oculomotor performance that was indistinguishable from age-matched controls. Only PSP patients displayed abnormalities in saccade velocity, whereas abnormalities in saccade gain were observed in PSP > CBS > Alzheimer's disease subjects. All patient groups except those with SD were impaired on the anti-saccade task, however only the FTLD subjects and not Alzheimer's disease, CBS or PSP groups, were able to spontaneously self-correct anti-saccade errors as well as controls. Receiver operating characteristic statistics demonstrated that oculomotor findings were superior to neuropsychological tests in differentiating PSP from other disorders, and comparable to neuropsychological tests in differentiating the other patient groups. These data suggest that oculomotor assessment may aid in the diagnosis of FTLD and related disorders.
doi:10.1093/brain/awn047
PMCID: PMC2367697  PMID: 18362099
oculomotor; frontotemporal lobar degeneration; corticobasal syndrome; progressive supranuclear palsy; Alzheimer's disease

Results 1-4 (4)