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+.左侧空间忽视（left spatial neglect, N+）的右脑损伤（Right Brain-Damaged, RBD）患者，其核心特征为无法定向及重定向注意力至病灶对侧的左侧空间刺激。在一项近期开展的视觉刺激事件相关电位（Event-Related Potentials, ERPs）研究（Lasaponara等人，2018）中，我们曾指出，N+患者的病理性注意偏向表现为：病灶同侧右侧空间内的靶刺激会引发过度的新奇反应与情境更新，而病灶对侧左侧空间内的靶刺激则表现为新奇反应与情境更新减弱。 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-蓝斑活动以及对意外事件/奖赏做出反应的可靠生物标志物。相较于中性靶刺激与有效靶刺激，N+患者在响应左侧空间内的罕见无效靶刺激时，其PDil出现病理性降低；而健康对照（Healthy Controls, HC）与无忽视的右脑损伤患者（N-），对这类靶刺激的PDil水平则高于中性靶刺激与常见有效靶刺激。所有实验组在响应右侧空间内的无效靶刺激时，其PDil均出现增强。 值得注意的是，N-与N+患者在左侧、右侧空间内均出现了数量一致的目标遗漏现象。相较于被感知到的靶刺激，N-患者在响应左侧与右侧空间内未被感知到的靶刺激时，其PDil均出现降低。与之相反，N+患者仅在左侧空间内响应未被感知的靶刺激时PDil降低，而右侧空间内被感知与未被感知的靶刺激所诱发的PDil水平相当。 本研究首次揭示了左侧空间忽视患者空间注意相关的PDil特征，并提示N+患者所存在的病理性注意偏向，可能会增强其对病灶同侧空间内未被感知刺激的自主神经反应（以PDil为表征）。这种增强效应会偏向同侧空间内的情境更新与刺激预测编码，进而加剧N+患者的病理性注意偏向。