The ability to select relevant information for our environment is considered the basis of all cognitive functions (Rosenberg et al., 2016; Kim and Kastner, 2019), and is frequently influenced by neurological/neurosurgical diseases. Selective attention, which is a core component of attention, can direct specific modalities, spaces, and features at the expense of other disturbances (Mueller et al., 2017). To do so, they need to direct attention voluntarily to appropriate stimuli toward the target (Corbetta and Shulman, 2002; Buschman and Miller, 2007; Mok et al., 2019). Additionally, selective attention requires inhibition of others’ interference to direct attention toward a specific one (Mueller et al., 2017).

Several brain areas are known to be involved in selective attention, such as the dorsolateral and inferior prefrontal cortices; medial prefrontal cortices, especially the dorsal anterior cingulate cortex (CC); orbito-frontal cortex; inferior parietal lobule; and superior temporal cortex (Hopfinger et al., 2000; Schulz et al., 2011; Mansouri et al., 2020). At the subcortical level, the frontoparietal network, namely the superior longitudinal fasciculus (SLF) and fronto-striatal circuit, are known to be involved in selective attention (Thiebaut de Schotten et al., 2011; Marshall et al., 2015; Naaijen et al., 2018). Among these, the anterior CC plays a central role in selective attention, specifically voluntary attentional control (Zhang et al., 2017; Mok et al., 2019), and it monitors appropriate action to achieve high-level goals with merging cognitive, sensorimotor, and incentive signals (Botvinick et al., 1999; Schulz et al., 2011). Regarding lateralization, although some of the past research emphasized the importance of the right hemisphere for attention function, there is no consensus to date (Heilman and Van Den Abell, 1980; Posner and Petersen, 1990; Nobre et al., 1997; Corbetta, 1998; Corbetta and Shulman, 2002). However, previous studies on patients with brain damage demonstrated that attention functional deficits tend to be found after damage to the right side, rather than the left side (Nobre et al., 1997; Wang et al., 2016; Agosta et al., 2017; Spaccavento et al., 2019). Additionally, participants with a larger tract volume of the right SLF than those on the left side had a higher ability to regulate selective attention (Marshall et al., 2015). These results might indicate that the right hemisphere plays a critical role in attention function, even though selective attention is governed by the bilateral hemispheres.

In this context, lesion studies, including brain tumor surgery, can provide insight into changes that might occur in the absence of a specific brain region. For instance, in patients who underwent cingulotomy for intractable pain or mental illness, selective attention was damaged following surgery, whereas other neuropsychological functions such as general intelligence, language, memory, and motor skills were mostly intact (Lenhard et al., 2005; Yen et al., 2009). This is also evidence that the anterior CC plays a critical role in the selective attentional network. However, attentional deficits are not necessarily elicited, even though a part of the anterior CC is damaged locally (Baird et al., 2006).

In the current study, we hypothesized that damage to specific parts of the right cerebral hemisphere, especially the CC, causes prolonged selective attentional deficits. We then examined the selective attention of patients with focal brain damage in right cerebral hemispheric brain tumors. Here, we used two types of assessment of selective attention, the cancelation test and color Stroop test, but the aspects assessed by each test are slightly different. In the cancelation test, participants are required to focus their attention on a specific stimulus intentionally while actively ignoring distractor stimuli (Lezak, 1995; Casco et al., 1998; Trevino et al., 2021). In contrast, the Stroop test is an assessment of selective attention involving attentional control or inhibition (Treisman and Fearnley, 1969; Graf et al., 1995). Consequently, we found that simultaneous damage of the anterior part of the anterior CC zone II and FST causes a prolonged deficit of selective attention, and these regions might be critical areas in the selective attention system.

In the present study, we investigated the regions that play a critical role in selective attention in right cerebral hemispheric brain tumors. We found that simultaneous damage to both the right CC zone II and FST cause a prolonged deficit in selective attention. Therefore, CC zone II and FST may be considered as key areas for selective attentional networks.

The central roles of the CC are high-level processing and selection, such as emotional function, sense of pain, and cognitive control and/or goal-directed attention (Shackman et al., 2011; Bubb et al., 2018; Touroutoglou et al., 2019). Specifically, zone II might be a key structure for selective attention, since damage to the region caused prolonged deficits in selective attention in the current study. Previously, it was known that CC is one of the central areas of selective attention. For instance, previous neuroimaging and neurophysiological studies and direct electrical stimulation during brain tumor surgery revealed the related brain regions such as the frontal lobe including the CC, dolso-lateral prefrontal cortex, and inferior frontal gyrus, in the Stroop test (Goethals et al., 2004; Wager et al., 2013; Song and Hakoda, 2015; Zhang et al., 2017; Heidlmayr et al., 2020). In particular, the CC plays an important role in tasks that require selective attention with cognitive control, such as the Stroop test (Wager et al., 2013; Heidlmayr et al., 2020). On the other hand, it is not common knowledge that CC zone II plays a central role in selective attention. To support our results, a meta-analysis indicated that the right hemispheric regions, including the middle part of the CC, play a role in inhibitory control during selective tasks, independent of the task types (Zhang et al., 2017). Moreover, some previous reports revealed that the CC plays important role in selective attention, and its location of significant region on neuroimaging results corresponds to the CC zone II (Silton et al., 2011; White et al., 2018). Beyond attentional function, some authors have revealed the importance of zone II within the CC, corresponding to the middle CC for various kinds of function. For instance, a meta-analysis including 380 activation foci from 192 studies found that the anterior part of the middle CC was the unique region that activates every functional domain (Shackman et al., 2011). Therefore, the anterior part of the CC zone II is considered a hub of cognitive and behavioral control, in particular selective attention (Shackman et al., 2011; Touroutoglou et al., 2019).

In the current study, the CC as well as the FST played a critical role in selective attention. Previously, the fronto-striatal circuit was known to play a critical role in the attentional network (Arnsten and Rubia, 2012; van Ewijk et al., 2012). Specifically, previous DTI studies revealed that abnormality of structural connectivity in the FST is associated with attentional deficits in patients with attention-deficit hyperactivity disorder (ADHD) (Silk et al., 2009; Konrad et al., 2010; van Ewijk et al., 2012). Moreover, a meta-analysis revealed that the fronto-striatal circuit underlies response inhibition, such as the Go/No-Go task (Zhang et al., 2017).

Interestingly, our results revealed that simultaneous damage to the FST and CC zone II caused a prolonged attentional deficit over 3 months postoperatively. Recently, it has been shown that there is functional connectivity between the fronto-striatal circuit and anterior CC (Naaijen et al., 2018; Hammes et al., 2019). Among the fronto-striatal circuits, reduced functional connectivity between the anterior CC and the striatum may cause an attentional deficit in ADHD (Hammes et al., 2019). Generally, deficits in neurological/neuropsychological function following brain tumor surgery tend to be temporary and have the ability to recover (Nakajima et al., 2017). Particularly, functions that are governed by extensive brain networks, such as attention, are more likely to recover, even though some of them are damaged (Price and Friston, 2002). Considering all these facts, simultaneous damage of two key areas might result in irreversible damage.

There are some potential methodological limitations. First, we were able to use only a limited number of assessments for attention since we performed these tests as a part of standard care during the perioperative period. In line with this, we focused on right hemispheric brain tumors in the current study, since the right hemisphere is considered to play an important role in the attentional network (Agosta et al., 2017; Spaccavento et al., 2019). Another reason for focusing on the right side is that it is difficult to assess attentional function of right and left lesioned patients using same test battery, since the cause for declining test score of left hemispheric brain tumors are sometimes different from that of right side (e.g., aphasia or alexia) (Spaccavento et al., 2019). Second, since the purpose of the current study was to investigate the influence of the resected area by investigating the relationship between focal brain resection and function, the attentional score should be based on the baseline. Therefore, some of the patients in the normal group had impairment when their scores were compared with those of the age-matched controls (Supplementary Table 1, asterisk). Finally, radiation therapy may induce delayed decline of cognitive function (Tanriverdi et al., 2016). Recent study has demonstrated that the impact of irradiation to white matter appears in 6 months after irradiation and cognitive function declines much later (Chapman et al., 2016). Considering these facts, the possibility that radiation therapy influenced attentional deficit in our patient group was low since the observation period in current study was 3 months. Moreover, there was no significant difference in the attentional scores of the six patients who received radiotherapy compared to those who did not in our patient group (Supplementary Figure 5). Further study will be required using a large number of patients with well controlled group in the future.

We revealed that zone II of the right CC and FST may be one of critical area in the selective attentional network, and concurrent damage of these regions might cause long-term deficit of selective attention. Lesion studies of patients who underwent focal brain resection are considered a unique method to understand key areas of the brain network.

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.

This study was performed according to the guidelines of the Internal Review Board of Kanazawa University and was approved by the Medical Ethics committee of Kanazawa University (approval numbers 1,797 and 3,160). The patients/participants provided their written informed consent to participate in this study.

MN and RN: conception and design, drafting article. RN: acquisition of data. RN and MK: analysis and interpretation of data. MN: study supervision. All authors critically revising the article and reviewed final version of the manuscript and approved it for submission.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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