The influence of deep brain stimulation on eye movements in Parkinson’s Disease: Modulation of visual attention by DBS during visual search

TY - CHAP

T1 - The influence of deep brain stimulation on eye movements in Parkinson’s Disease: Modulation of visual attention by DBS during visual search

AU - Keyser, Johannes

AU - Fischer, Petra

AU - Gulberti, Alessandro

AU - Ossandón, José P

AU - Moll, Christian

AU - Engel, Andreas Karl

AU - König, Peter

N1 - Conference code: 24

PY - 2014/2/21

Y1 - 2014/2/21

N2 - Deep brain stimulation (DBS) effectively reduces motor symptoms of Parkinson’s disease (PD). Research is increasingly directed toward possible effects on associated cognitive deficits. Here, we tested if DBS of the ventral part of the subthalamic nucleus (STN) and subjacent substantia nigra pars reticulata (SNr) influences subclinical signs of neglect in PD patients. Our hypothesis was derived from the SNr’s well-established role as the basal ganglia’s main output foreye-movement control. We recruited non-demented, advanced PD patients with left-dominant motor symptoms and healthy, age- matched controls. Four different DBS conditions were tested: 1) bilateral DBS of the STN (clinical DBS); 2) no stimulation (DBS off) and two unilateral settings targeting the ventral STN/SNr, including 3) ventral left; and 4) ventral right stimulation. We investigated top- down controlled visual search for a target "O" among distractors "Q" within a grid of 6x6 symbols. Upon target detection, subjects pressed a button. Concurrent gaze-tracking enabled detailed analysis of eye movements. Trial duration was set individually to yield an expected target detection rate of 75%. Resulting mean target detection varied around 70% (66-74%), without a clear difference between subject groups. This deviance from expectation is largely due to false positive button presses (i.e. mismatch of gaze location and target position). Compared with DBS off and ventral left, target detection rate increased by 7.8% (0.6-14.3%) during ventral right DBS. Additionally, search duration until target fixation was 1.3s (0.7-1.9s) longer for patients than for controls. Slightly longer fixation durations and hypometric saccades in patients only provide partial explanations for this difference. In fact, compared with control subjects, patients required about three additional fixations to arrive at the target. Interestingly, patients re-fixated previously inspected distractors 2.6 times (2.0-3.7x) more often than controls. Furthermore, search times decreased toward the right hemifield in patients, while controls showed an opposite bias. However, DBS did not influence this bias in patients. In summary, we confirmed signs of left-sided neglect--expressed as negative gradient in search durations--in PD patients with left sided motor symptoms. This bias was not significantly influenced by DBS, possibly because subjects engaged in top-down rather than bottom- up driven exploration. However, ventral right DBS significantly improved patients’ search performance, consistent with the view of a right-lateralized involvement of basal ganglia in visual attention. The largest difference between patients and controls was, however, observed in overall search time. This difference cannot simply be attributed to motor deficits but rather may reflect differences in scanning strategies and deployment of attention. Acknowledgements: This study is supported by the EU (FP7-ICT- 270212 and ERC-2010-AdG-269716).

AB - Deep brain stimulation (DBS) effectively reduces motor symptoms of Parkinson’s disease (PD). Research is increasingly directed toward possible effects on associated cognitive deficits. Here, we tested if DBS of the ventral part of the subthalamic nucleus (STN) and subjacent substantia nigra pars reticulata (SNr) influences subclinical signs of neglect in PD patients. Our hypothesis was derived from the SNr’s well-established role as the basal ganglia’s main output foreye-movement control. We recruited non-demented, advanced PD patients with left-dominant motor symptoms and healthy, age- matched controls. Four different DBS conditions were tested: 1) bilateral DBS of the STN (clinical DBS); 2) no stimulation (DBS off) and two unilateral settings targeting the ventral STN/SNr, including 3) ventral left; and 4) ventral right stimulation. We investigated top- down controlled visual search for a target "O" among distractors "Q" within a grid of 6x6 symbols. Upon target detection, subjects pressed a button. Concurrent gaze-tracking enabled detailed analysis of eye movements. Trial duration was set individually to yield an expected target detection rate of 75%. Resulting mean target detection varied around 70% (66-74%), without a clear difference between subject groups. This deviance from expectation is largely due to false positive button presses (i.e. mismatch of gaze location and target position). Compared with DBS off and ventral left, target detection rate increased by 7.8% (0.6-14.3%) during ventral right DBS. Additionally, search duration until target fixation was 1.3s (0.7-1.9s) longer for patients than for controls. Slightly longer fixation durations and hypometric saccades in patients only provide partial explanations for this difference. In fact, compared with control subjects, patients required about three additional fixations to arrive at the target. Interestingly, patients re-fixated previously inspected distractors 2.6 times (2.0-3.7x) more often than controls. Furthermore, search times decreased toward the right hemifield in patients, while controls showed an opposite bias. However, DBS did not influence this bias in patients. In summary, we confirmed signs of left-sided neglect--expressed as negative gradient in search durations--in PD patients with left sided motor symptoms. This bias was not significantly influenced by DBS, possibly because subjects engaged in top-down rather than bottom- up driven exploration. However, ventral right DBS significantly improved patients’ search performance, consistent with the view of a right-lateralized involvement of basal ganglia in visual attention. The largest difference between patients and controls was, however, observed in overall search time. This difference cannot simply be attributed to motor deficits but rather may reflect differences in scanning strategies and deployment of attention. Acknowledgements: This study is supported by the EU (FP7-ICT- 270212 and ERC-2010-AdG-269716).

M3 - Conference contribution - Poster

BT - NCM 24TH Annual Meeting

T2 - 24th Annual Meeting for the Society for the Neural Control of Movement

Y2 - 22 April 2014 through 26 April 2014

ER -