A theory of brain-computer interface learning via low-dimensional control.

A remarkable demonstration of the flexibility of mammalian motor systems is primates' ability to learn to control brain-computer interfaces (BCIs). This constitutes a completely novel motor behavior, yet primates are capable of learning to control BCIs under a wide range of conditions. BCIs with carefully calibrated decoders, for example, can be learned with only minutes to hours of practice. With a few weeks of practice, even BCIs with randomly constructed decoders can be learned. What are the biological substrates of this learning process? Here, we develop a theory based on a re-aiming strategy, whereby learning operates within a low-dimensional subspace of task-relevant inputs driving the local population of recorded neurons. Through comprehensive numerical and formal analysis, we demonstrate that this theory can provide a unifying explanation for disparate phenomena previously reported in three different BCI learning tasks, and we derive a novel experimental prediction that we verify with previously published data. By explicitly modeling the underlying neural circuitry, the theory reveals an interpretation of these phenomena in terms of biological constraints on neural activity.

Brain-computer interface control along instructed paths.

OBJECTIVE: Brain-computer interfaces (BCIs) are being developed to assist paralyzed people and amputees by translating neural activity into movements of a computer cursor or prosthetic limb. Here we introduce a novel BCI task paradigm, intended to help accelerate improvements to BCI systems. Through this task, we can push the performance limits of BCI systems, we can quantify more accurately how well a BCI system captures the user's intent, and we can increase the richness of the BCI movement repertoire. APPROACH: We have implemented an instructed path task, wherein the user must drive a cursor along a visible path. The instructed path task provides a versatile framework to increase the difficulty of the task and thereby push the limits of performance. Relative to traditional point-to-point tasks, the instructed path task allows more thorough analysis of decoding performance and greater richness of movement kinematics. MAIN RESULTS: We demonstrate that monkeys are able to perform the instructed path task in a closed-loop BCI setting. We further investigate how the performance under BCI control compares to native arm control, whether users can decrease their movement variability in the face of a more demanding task, and how the kinematic richness is enhanced in this task. SIGNIFICANCE: The use of the instructed path task has the potential to accelerate the development of BCI systems and their clinical translation.

p16 gene methylation in colorectal cancers associated with Duke's staging.

AIM: To explore the association of methylation of the CpG island in the promotor of the p16 tumor suppressor gene with the clinicopathological characteristics of the colorectal cancers. METHODS: Methylation-specific PCR (MSP) was used to detect p16 methylation of 62 sporadic colorectal cancer specimens. RESULTS: p16 methylation was detected in 42% of the tumors.Dukes'staging was associated with p16 methylation status.p16 methylation occurred more frequently in Dukes'C and D patients (75.9%) than in Dukes'A and B patients (12.1%). CONCLUSION: p16 methylation plays a role in the carcinogenesis of a subset of colorectal cancer, and it might be linked to poor prognosis.

[Evaluation of combined CA-19-9 and CEA assay in monitoring recurrences and metastases of colorectal cancer].

The results of combined CA-19-9 CEA assay were measured in 216 cases of colorectal cancer. In 28 preoperative patients, the positive rate 16.67% in Dukes' A group, 25% in B, 55% in C and 40% in D. It was proved less valuable in early diagnosis. The positive CA-19-9 alone in 66 with relapsed or metastases out of 182 undergoing radical resection was 63.63%, CEA alone 62.12%, and combined assay 86.36%. The false positive rate of CA-19-9 and CEA was 6.03% and combined assay 11.21%. In 27 palliative resections CA-19-9 in 40.74% cases, CEA in 44.44%, and combined assay in 59.2% was positive. In cases of nonresectable tumors, the positive rate was 66.7%, 66.7% and 83.33%, respectively. There was no definite correlation between the value of CA-19-9 and CEA. The data showed significantly higher sensitivity in combined assay than in either CA-19-9 or CEA alone. Combined assay with the sensitivity of 86.36% and the specificity of 88.79%, was more useful in finding of postoperative. recurrences or metastases. We suggest that this method should be used routinely in monitoring postoperative patients with colorectal cancer.

[Surgical treatment of carcinoma of the middle and lower rectum. Report of 949 cases].

Carcinoma of the rectum in 949 cases (484 cases of middle rectum and 465 cases of lower rectum) was resected from 1954 to 1986. There were 296 (31.99%) cases of sphincter-saving resection (SSR). The results of SSR before 1980 were compared with those after 1980. The operative mortality of curative resection decreased from 1.52% to 0.34%. The overall survival rate was 74.20 +/- 2.16% (life table method), for abdominoperineal resection (A-P resection) was 61.67 +/- 3.62% and for SSR was 84.12 +/- 2.40% Respectively. The local recurrence after curative resection in all cases was 14.02%, after A-P resection-15.44%, and after SSR-10.92%. The local recurrence after SSR before 1980 was just the same as after 1980. The results in this series showed the rationality of SSR in the treatment of carcinoma of the middle and lower rectum.

[Surgical treatment of acute intestinal obstruction caused by large bowel carcinoma].

In the past 30 years 338 patients with colorectal carcinoma were admitted for acute intestinal obstruction which accounted for 17.17% of 1969 surgically treated colorectal carcinomas. Of these, right colon carcinoma was found in 116 cases, left colon carcinoma in 177, and rectal carcinoma in 45. Sixty nine one-stage resections of the tumor out of 148 emergent operations were carried out including all 29 right colon carcinomas, 20 out 34 left colon carcinomas, and 4 out of 6 rectal carcinomas. In patients undergoing one-stage resections, the overall operative mortality was 3.77%, morbidity happened in one case suffering from anastomotic leakage, and the five year survival rate was 43.4% compared with no operative mortality, and five year survival of only 18.75% in delayed resection group. Our data showed that the mortality of one stage resection of left colon carcinomas complicated with acute obstruction was acceptable and the five year survival rate was slightly higher than that in delayed resection. In terms of whole series, the five year survival rate in one stage resection group was significantly higher than that in delayed resection group. The authors, therefore, favour one stage resection of the tumor in cases of acute intestinal obstruction.

[Route and preparation of 5-Fu administration as preoperative adjuvant chemotherapy in rectal cancer. II. Morphologic, ultrastructural and histochemical changes of the cancer cells after intrarectal and intravenous 5-Fu administration].

From March 1981 to October 1985, 5-Fu was preoperatively given to 65 Dukes B and C rectal cancer patients (intrarectal suppository 40 and emulsion 20, intravenous 5). The results indicated that after intrarectal administration, marked changes and destruction of the cancer cells in morphology were observed in 40% of the resected rectal specimens for suppository and in 45% for emulsion; marked retrograde degeneration in ultrastructure was found in 47.5% for suppository and in 50% for emulsion; DNA synthesis was obviously reduced in 63% for suppository and in 75% for emulsion. It is suggested that the emulsion be a better preparation. No obvious changes or destruction in morphology and ultrastructure were observed in cancer cells treated by intravenous drip of high dose 5-Fu though leukopenia below 4000 was found in 2/5. However, it was 0/60 by rectal administration. This implies that the intrarectal route is more rational than the conventional intravenous route. This study presents an alternate supplementary treatment in addition to radiotherapy for the reduction of postoperative local recurrence of Dukes B and C rectal cancers.

[Route and preparation of 5-Fu administration as preoperative adjuvant chemotherapy in rectal cancer. I. Concentration and distribution of 5-Fu in tissues monitored by 14C-isotopically tagged 5-Fu].

Experimental studies on more rational route and preparation of preoperative administration of 5-Fu were undertaken from March 1981 to June 1985. The experimental observation shows that intrarectal administration of radioisotope 14C tagged 5-Fu (suppository and emulsion) produces a much higher concentration in the rectal wall and mesenteric lymph nodes compared with its intravenous administration (40 rabbits) and produces a much higher concentration in cancer tissue than in surrounding tissues and in mesenteric lymph nodes than in the inferior mesenteric veins (4 patients). These findings favor the attenuation or destruction of cancer cells in the tumor and regional lymph nodes-the main route of spread. Also, after intrarectal administration of 14C tagged 5-Fu, its concentration in the lung, liver and bone marrow is much lower than that after intravenous administration (40 rabbits), and hence systemic toxicity is decreased. The above results indicate that the intrarectal route stands better than the conventional intravenous route for 5-Fu preoperative adjuvant chemotherapy in rectal cancer. Administration of 5-Fu emulsion produces a higher concentration in the rectal wall and mesenteric lymph nodes than that of 5-Fu suppository and peak concentration also appears earlier, i.e. 2 hours after the administration of 5-Fu emulsion. This will lessen the interference of 5-Fu absorption owing to its premature evacuation, indicating that emulsion is a better form for intrarectal 5-Fu.

Surgical treatment and late results in 1226 cases of colorectal cancer.

One thousand two hundred twenty-six cases of colorectal cancer were treated surgically between 1956 and 1978. Seven hundred ninety-eight cases (65.08 per cent) were rectal, 74.3 per cent of which were located extraperitoneally. Dukes' C2 cases and cases with distant metastasis constituted 39.15 per cent, and Dukes' A cases, 9.22 per cent. Resectability rate was 75.1 per cent (77.6 per cent for rectal cancer). Two hundred and four cases (32.96 per cent) of rectal excision were restorative resections. Of the combined excisions for extraperitoneal lesions in females, 84.8 per cent were posterior pelvic exenterations. The overall operative mortality rate was 2.93 per cent. The mortality rate for 921 cases of resection was 1.73 per cent, for rectal resection, 0.8 per cent, and for curative rectal resection, 0.63 per cent. The follow-up rate was 94.13 per cent. The five-and ten-year survival rates for rectal resection were 53.08 +/- 2.29 per cent and 47.65 +/- 2.44 per cent; for curative rectal resection. 66.91 +/- 2.54 per cent and 60.27 +/- 3.03 per cent; and for Dukes' A cases, 98.05 +/- 1.35 per cent and 96.39 +/- 2.13 per cent. The five-and ten-year survival rates for colonic resection were 59.79 +/- 2.04 per cent and 52.18 +/- 3.49 per cent; for curative colonic resection, 72.79 +/- 3.39 per cent and 62.06 +/- 4.17 per cent; and for Dukes' A cases, both 100 per cent. Besides the extent of spread and degree of malignancy of a lesion, the local immunologic reaction of the host is also important in prognosis. The more lymphocytic infiltration in and around the cancer, the more follicular hyperplasia and sinus histiocytosis in regional lymph nodes, the better is the prognosis. The problem of anal preservation in radical resection of rectal cancer and the problem of improvement of results in the treatment of extraperitoneal rectal cancer are discussed in detail.

Alterations in kinins of coronary blood from rat heart homografts.

Forty-eight heterotopic heart transplants (33 homografts and 15 isografts) were performed in inbred rats. Levels of kallikrein, prekallikrein, and kallikrein inhibitor were determined in coronary sinus venous blood of grafted hearts at various intervals postgrafting. Homograft observations were assessed against those in nonrejecting isografts. Significant increases in homograft prekallikrein level on day 4 were followed by significant increases in homograft kallikrein activity on day 6. Kallikrein inhibitor levels in homografts were consistently increased in relation to isograft levels. Kallikrein and inhibitor activity showed an inverse relationship in their respective changes. High levels of kallikrein and prekallikrein occurred in homografts ten days posttransplantation. Immunological rejecting homografts showed meaningful changes in the activity of kinin-forming substances known to participate in inflammation.