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+.伴左侧空间忽视（left spatial neglect, N+）的右脑损伤（Right Brain-Damaged, RBD）患者，其核心特征为难以将注意力定向并重新定向至空间损伤对侧的左侧区域的刺激。在一项近期采用视觉刺激的事件相关电位（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：对右侧同侧损伤空间内的目标存在过度的新奇反应与情境更新，而对左侧损伤对侧空间内的目标则表现出减弱的新奇反应与情境更新。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）——这是反映去甲肾上腺素能蓝斑核活动及对意外事件/奖赏响应的可靠生物标志物。与中性目标及有效目标相比，N+患者在响应空间左侧的少见无效目标时，其PDil出现病理性降低；而健康对照组（Healthy Controls, HC）与无忽视的右脑损伤患者（RBD without neglect, N-），对这类无效目标的PDil则相较于中性目标与常见有效目标显著升高。空间右侧的无效目标则可使所有实验组的PDil水平升高。值得注意的是，N-与N+患者均在空间左右两侧区域出现了数量相近的目标遗漏。相较于可见目标，N-患者对空间左右两侧的不可见目标的PDil均出现降低。与之相反，N+患者仅在响应空间左侧的不可见目标时出现PDil降低；而在空间右侧，可见与不可见目标引发的PDil水平无显著差异。本研究首次揭示了左侧空间忽视患者中与空间注意相关的PDil特征，并表明N+患者所存在的病理性注意偏向，可能会增强其对同侧损伤空间内不可见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损伤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。