In patients with damage to the primary visual cortex (V1), residual vision can guide goal-directed movements to targets in the blind field without awareness. This phenomenon has been termed ...blindsight, and its neural mechanisms are controversial. There should be visual pathways to the higher visual cortices bypassing V1, however some literature propose that the signal is mediated by the superior colliculus (SC) and pulvinar, while others claim the dorsal lateral geniculate nucleus (dLGN) transmits the signal. Here, we directly test the role of SC to ventrolateral pulvinar (vlPul) pathway in blindsight monkeys. Pharmacological inactivation of vlPul impairs visually guided saccades (VGS) in the blind field. Selective and reversible blockade of the SC-vlPul pathway by combining two viral vectors also impairs VGS. With these results we claim the SC-vlPul pathway contributes to blindsight. The discrepancy would be due to the extent of retrograde degeneration of dLGN and task used for assessment.
Abstract
Blindsight is the residual visuo-motor ability without subjective awareness observed after lesions of the primary visual cortex (V1). Various visual functions are retained, however, ...instrumental visual associative learning remains to be investigated. Here we examined the secondary reinforcing properties of visual cues presented to the hemianopic field of macaque monkeys with unilateral V1 lesions. Our aim was to test the potential role of visual pathways bypassing V1 in reinforcing visual instrumental learning. When learning the location of a hidden area in an oculomotor search task, conditioned visual cues presented to the lesion-affected hemifield operated as an effective secondary reinforcer. We noted that not only the hidden area location, but also the vector of the saccade entering the target area was reinforced. Importantly, when the visual reinforcement signal was presented in the lesion-affected field, the monkeys continued searching, as opposed to stopping when the cue was presented in the intact field. This suggests the monkeys were less confident that the target location had been discovered when the reinforcement cue was presented in the affected field. These results indicate that the visual signals mediated by the residual visual pathways after V1 lesions can access fundamental reinforcement mechanisms but with impaired visual awareness.
Responses of midbrain dopamine (DA) neurons reflecting expected reward from sensory cues are critical for reward-based associative learning. However, critical pathways by which reward-related visual ...information is relayed to DA neurons remain unclear. To address this question, we investigated Pavlovian conditioning in macaque monkeys with unilateral primary visual cortex (V1) lesions (an animal model of 'blindsight'). Anticipatory licking responses to obtain juice drops were elicited in response to visual conditioned stimuli (CS) in the affected visual field. Subsequent pharmacological inactivation of the superior colliculus (SC) suppressed the anticipatory licking. Concurrent single unit recordings indicated that DA responses reflecting the reward expectation could be recorded in the absence of V1, and that these responses were also suppressed by SC inactivation. These results indicate that the subcortical visual circuit can relay reward-predicting visual information to DA neurons and integrity of the SC is necessary for visually-elicited classically conditioned responses after V1 lesion.
Background
Iron deficiency anemia is represented in colorectal cancer (CRC) patients. Iron surplus load to increase non-transferrin bound iron (NTBI), and NTBI promotes cancer progression and ...influences microbiota. This study investigated whether preoperative serum iron status was associated with prognosis after CRC resection.
Methods
We evaluated preoperative iron and transferrin saturation (TSAT), which was calculated as iron divided by total iron-binding capacity, in 327 patients who underwent surgery for Stage II–III CRC. Fe < 60 μg/dl and TSAT > 40% were defined as low and high iron, respectively. The associations between iron status and overall survival (OS) were evaluated in univariate and multivariate Cox proportional hazards analysis.
Results
Of the 327 patients, 179 (54.7%), 124 (37.9%) and 24 (7.3%) had low, normal and high iron, respectively. In univariate analysis, low iron was associated with shorter OS (hazard ratio HR 2.821, 95% confidence interval CI 1.451–5.485,
P
= 0.002). High iron was also associated with shorter OS (HR 3.396, 95% CI 1.359–8.489,
P
= 0.009). In multivariate analysis, high age (
P
= 0.002), depth of invasion pT4 (
P
= 0.012), lymph-node metastasis presence (
P
= 0.035), low albumin (
P
= 0.011), low iron (HR 2.282, 95% CI 1.163–4.478,
P
= 0.016) and high iron (HR 3.757, 95% CI 1.486–9.494
P
= 0.005) were independently associated with shorter OS. High iron was associated with the amount of intratumoral
Fusobacterium nucleatum
compared with normal iron.
Conclusion
Both low and high preoperative iron in Stage II–III CRC patients were associated with unfavorable OS in univariate and multivariate analyses.
Background
Brain metastasis of colorectal cancer is infrequent, and isolated brain metastases are more infrequent. Thus, when neurological symptoms, such as paralysis or disturbance of consciousness ...appear, there is a high probability that the cancer has spread to other organs.
Case presentation
Here, we present a 64-year-old man with a progressive headache, decreased motivation, and aphasia who was diagnosed with a brain tumor in the left frontal region. He underwent a craniotomy, and the brain tumor was diagnosed as adenocarcinoma. We performed a colonoscopy and diagnosed rectal cancer without other distant metastases. After whole-brain radiotherapy (WBRT), low anterior resection for primary rectal tumor was performed using a robotic system. The patient was discharged in good condition and received postoperative adjuvant therapy for rectal cancer. He showed no signs of recurrence after 1 year of follow-up.
Conclusions
We described a rare case of rectal cancer that was diagnosed after resection of isolated brain metastasis. A good prognosis was achieved with surgery and WBRT.
Previous reports on ‘blindsight’ have shown that some patients with lesions of the primary visual cortex (V1) could localize visual targets in their scotoma with hand and/or eye movements without ...visual awareness. A role of the retino‐tectal pathway on residual vision has been proposed but the direct evidence for this still remains sparse. To examine this possibility, we inactivated the superior colliculus (SC) of unilateral V1‐lesioned monkeys using microinjections of muscimol, and analysed the effects on visually guided saccades. Following muscimol injections into the contralesional SC, the monkeys performed the visually guided saccade task with relatively minor deficits. The effects of ipsilesional SC inactivation were more severe. After injections, the monkeys failed to localize the target within the visual field represented at the injection site on the SC map. The effects of ipsilesional SC inactivation may result from sensory deficits, motor deficits or a combination of both. To examine these possibilities, we tested the effects of SC inactivation on the motor system by investigating spontaneous saccades. After inactivation of the ipsilesional SC, spontaneous saccades toward the injection site were not abolished, suggesting that impairment of visually guided saccades following inactivation of the ipsilesional SC could not be explained solely by a motor deficit and was primarily due to a visual deficit, presumably by interfering with processing in the superficial layer. We conclude that the retino‐tectal pathway plays an essential role in residual vision after V1 lesion. The results suggest that this pathway may be involved in mediating unconscious vision in blindsight patients.
Aim
This study aimed to investigate the prognosis after recurrence in patients with stage I–III colon cancer (CC) and rectal cancer (RC).
Methods
Cancer recurred in 116 (15.2%) out of 763 patients ...with stage I–III colorectal cancer. The overall survival (OS) after recurrence was evaluated based on the recurrence organs and patterns.
Results
The first recurrence occurred in the lungs, livers, lymph nodes, and other sites in 32, 22, 12, and 2 patients, respectively. It was localized, disseminated, and involved two or more organs in 14, 9, and 25 patients, respectively. Patients with CC had a shorter OS after recurrence as compared to those with RC (P = .0103). Compared to other organ metastasis, liver metastasis was associated with an earlier recurrence (P = .0026) and shorter OS after recurrence (hazard ratio HR: 2.216; 95% confidence interval CI: 1.052–4.459; P = .0370). Lung metastasis was associated with a more favorable prognosis as compared to other organ recurrences (HR: 0.338; 95% CI: 0.135–0.741; P = .0057). One‐organ recurrence and oligometastasis were observed in 78.4% and 49.1% of the patients, respectively. The 5‐y OS rates of patients with one‐organ recurrence and oligometastasis were 47.5% and 71.7%, respectively. Invasive treatment was associated with a favorable prognosis (P < .0001).
Conclusions
Liver metastasis and dissemination were associated with a shorter OS after recurrence. Approximately 50% of the patients experienced oligometastasis, which was associated with a favorable prognosis. Hence, to improve patient prognosis it is better to perform invasive treatments when possible.
One organ recurrence was observed in 78.4% of patients and oligometastasis in 49.1%. The 5‐y OS rates of patients with one organ recurrence and oligometastasis were 47.5% and 71.7%, respectively. Invasive treatment was associated with a favorable prognosis (P < .0001).
Aim
This study investigated whether preoperative serum transferrin, a rapid‐turnover protein, was associated with prognosis after colorectal cancer (CRC) resection.
Methods
We evaluated preoperative ...transferrin, which was calculated as iron and unsaturated iron‐binding capacity, in 501 patients who underwent surgery for Stage I–III CRC. Transferrin level was directly proportional to total iron‐binding capacity (TIBC), and TIBC < 250 μg/dl was defined as low transferrin. The associations between transferrin and prognosis were evaluated in univariate and multivariate Cox proportional hazards analyses.
Results
Fifty‐eight of 501 patients (11.5%) had low transferrin. In these patients, low transferrin was significantly associated with high age, female gender, low body mass index (<18.5), high white blood cell count, low total protein, low albumin, high C‐reactive protein, low hemoglobin, and low neutrophil/lymphocyte ratio. In the univariate analysis, low transferrin was associated with shorter relapse‐free survival (RFS) (hazard ratio HR 2.180, 95% confidence interval CI 1.417‐3.354, P < .001), overall survival (OS) (HR 2.930, 95% CI 1.784‐4.811, P < .001), and cancer‐specific survival (CSS) (HR 2.122, 95% CI 1.053‐4.275, P = .035). In multivariate analysis, high age (P < .001), Glasgow Prognostic Score (P = .009), and low transferrin (HR 2.336, 95% CI 1.173‐4.654, P = .011) were independently associated with shorter OS, and depth of invasion pT4 (P = .015), presence of lymph node metastasis (P = .001), low hemoglobin (P = .034), and low transferrin (HR 2.638, 95% CI 1.113‐5.043, P = .025) were independently associated with shorter CSS.
Conclusions
Preoperative serum transferrin in Stage I–III CRC patients was identified as a novel prognostic marker by univariate and multivariate analyses.
Fifty‐eight of 501 patients CRC patients (11.5%) had low transferrin, which is a rapid turnover protein. Preoperarive low transferrin was associated with shorter relapse‐free survival (P < .001), overall survival (P < .001), and cancer‐specific survival (P = .004) compared with normal transferrin. Preoperative serum transferrin was identified as a novel prognostic marker in univariate and multivariate analyses.
Patients with damage to the primary visual cortex (V1) lose visual awareness, yet retain the ability to perform visuomotor tasks, which is called "blindsight." To understand the neural mechanisms ...underlying this residual visuomotor function, we studied a non-human primate model of blindsight with a unilateral lesion of V1 using various oculomotor tasks. Functional brain imaging by positron emission tomography showed a significant change after V1 lesion in saccade-related visuomotor activity in the intraparietal sulcus area in the ipsi- and contralesional posterior parietal cortex. Single unit recordings in the lateral bank of the intraparietal sulcus (lbIPS) showed visual responses to targets in the contralateral visual field on both hemispheres. Injection of muscimol into the ipsi- or contralesional lbIPSs significantly impaired saccades to targets in the V1 lesion-affected visual field, differently from previous reports in intact animals. These results indicate that the bilateral lbIPSs contribute to visuomotor function in blindsight.
Monkeys with unilateral lesions of the primary visual cortex (V1) can make saccades to visual stimuli in their contralateral ("affected") hemifield, but their sensitivity to luminance contrast is ...reduced. We examined whether the effects of V1 lesions were restricted to vision or included later stages of visual-oculomotor processing. Monkeys with unilateral V1 lesions were tested with a visually guided saccade task with stimuli in various spatial positions and of various luminance contrasts. Saccades to the stimuli in the affected hemifield were compared with those to the near-threshold stimuli in the normal hemifield so that the performances of localization were similar. Scatter in the end points of saccades to the affected hemifield was much larger than that of saccades to the near-threshold stimuli in the normal hemifield. Additional analysis revealed that this was because the initial directional error was not as sufficiently compensated as it was in the normal hemifield. The distribution of saccadic reaction times in the affected hemifield tended to be narrow. We modeled the distribution of saccadic reaction times by a modified diffusion model and obtained evidence that the decision threshold for initiation of saccades to the affected hemifield was lower than that for saccades to the normal hemifield. These results suggest that the geniculostriate pathway is crucial for on-line compensatory mechanisms of saccadic control and for decision processes. We propose that these results reflect deficits in deliberate control of visual-oculomotor processing after V1 lesions, which may parallel loss of visual awareness in human blindsight patients.
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