Pupil dilation during orienting of attention and conscious detection of visual targets in patients with left spatial neglect

Right Brain-Damaged patients (RBD) with left spatial neglect (N+), are characterised by deficits in orienting and re-orienting attention to stimuli in the contralesional left side of space. In a recent ERPs study with visual stimuli (Lasaponara et al., 2018) we have pointed out that the pathological attentional bias of N+ is matched with exaggerated novelty reaction and contextual updating of targets in the right ipsilesional space and reduced novelty reaction and contextual updating of targets in the left contralesional space. To characterise further the attentional performance of N+, here we measured Pupil Dilation (PDil), which is a reliable marker of noradrenergic-locus coeruleus activity and response to unexpected events/rewards. Compared to Neutral and Valid targets, N+ patients displayed a pathological reduction of PDil in response to infrequent Invalid targets in the left side of space, while in Healthy Controls (HC) and RBD without neglect (N-) the same targets enhanced PDil with respect to Neutral and frequent Valid targets. Invalid targets in the right side of space enhanced PDil in all experimental groups. Interestingly, both N- and N+ showed a consistent number of target omissions both in the left and right side of space. With respect to seen targets, N- showed reduced PDil in response to unseen targets both in the left and right side of space. In contrast, N+ had reduced PDil in response to unseen targets in the left side of space though not in the right side, where seen and unseen targets evoked comparable levels of PDil. These results disclose, for the first time, the PDil correlates of spatial attention in left spatial neglect and suggest that the pathological attentional bias suffered by N+ might enhance the autonomic responses reflected in PDil to unseen ipsilesional stimuli. This enhancement can contribute to biasing contextual updating and predictive coding of stimuli in the ipsilesional space, thus worsening the pathological attentional bias of N+.

右半球脑损伤（Right Brain-Damaged, RBD）伴左侧空间忽视（Left Spatial Neglect, N+）的患者，其核心特征为无法定向并重新将注意力分配至空间对侧（左侧）的刺激。在一项采用视觉刺激的近期事件相关电位（Event-Related Potentials, ERPs）研究（Lasaponara等，2018）中，我们曾指出，N+患者的病理性注意偏向表现为：对右侧同侧空间内的靶刺激存在过度的新异反应与情境更新，而对左侧对侧空间内的靶刺激的新异反应与情境更新则显著减弱。为进一步刻画N+患者的注意表现，本研究测量了瞳孔扩张（Pupil Dilation, PDil）——这是去甲肾上腺素能蓝斑核活动及对意外事件/奖赏的反应的可靠生物标志物。与中性靶刺激及有效靶刺激相比，N+患者在响应空间左侧的非频繁无效靶刺激时，其瞳孔扩张出现病理性减弱；而健康对照（Healthy Controls, HC）及无空间忽视症状的右半球脑损伤患者（N-），此类靶刺激相较于中性靶刺激与频繁有效靶刺激，可引发更强的瞳孔扩张反应。空间右侧的无效靶刺激则可在所有实验组中引发增强的瞳孔扩张。值得注意的是，N-与N+患者均在空间左右两侧出现了数量相当的靶刺激漏报。相较于可见靶刺激，N-患者在响应左右两侧的不可见靶刺激时，瞳孔扩张均出现减弱。与之相反，N+患者仅在响应空间左侧的不可见靶刺激时出现瞳孔扩张减弱，而在右侧空间中，可见与不可见靶刺激引发的瞳孔扩张水平相当。本研究结果首次揭示了左侧空间忽视患者空间注意相关的瞳孔扩张特征，并表明N+患者所经历的病理性注意偏向，可能会增强其对同侧空间内不可见刺激的自主神经反应（以瞳孔扩张为体现）。这种增强效应可能会对同侧空间内刺激的情境更新与预测编码产生偏倚，进而加剧N+患者的病理性注意偏向。