Task-Dependent Behavioral Dynamics Make the Case for Temporal Integration in Multiple Strategies during Odor Processing.

Differing results in olfactory-based decision-making research regarding the amount of time that rats and mice use to identify odors have led to some disagreements about odor-processing mechanics, including whether or not rodents use temporal integration (i.e., sniffing longer to identify odors better). Reported differences in behavioral strategies may be due to the different types of tasks used in different laboratories. Some researchers have reported that animals performing two-alternative choice (TAC) tasks need only 1-2 sniffs and do not increase performance with longer sampling. Others have reported that animals performing go/no-go (GNG) tasks increase sampling times and performance for difficult discriminations, arguing for temporal integration. We present results from four experiments comparing GNG and TAC tasks over several behavioral variables (e.g., performance, sampling duration). When rats know only one task, they perform better in GNG than in TAC. However, performance was not statistically different when rats learned and were tested in both tasks. Rats sample odors longer in GNG than in TAC, even when they know both tasks and perform them in the same or different sessions. Longer sampling is associated with better performance for both tasks in difficult discriminations, which supports the case for temporal integration over ≥2-6 sniffs in both tasks. These results illustrate that generalizations from a single task about behavioral or cognitive abilities (e.g., processing, perception) do not capture the full range of complexity and can significantly impact inferences about general abilities in sensory perception.SIGNIFICANCE STATEMENT Behavioral tasks and training and testing history affect measured outcomes in cognitive tests. Rats sample odors longer in a go/no-go (GNG) than in a two-alternative choice (TAC) task, performing better in GNG unless they know both tasks. Odor-sampling time is extended in both tasks when the odors to be discriminated are very similar. Rats may extend sampling time to integrate odor information up to ∼0.5 s (2-6 sniffs). Such factors as task, task parameters, and training history affect decision times and performance, making it important to use multiple tasks when making inferences about sensory or cognitive processing.

Gamma and Beta Oscillations Define a Sequence of Neurocognitive Modes Present in Odor Processing.

UNLABELLED: Olfactory system beta (15-35 Hz) and gamma (40-110 Hz) oscillations of the local field potential in mammals have both been linked to odor learning and discrimination. Gamma oscillations represent the activity of a local network within the olfactory bulb, and beta oscillations represent engagement of a systemwide network. Here, we test whether beta and gamma oscillations represent different cognitive modes using the different demands of go/no-go and two-alternative choice tasks that previously were suggested to favor beta or gamma oscillations, respectively. We reconcile previous studies and show that both beta and gamma oscillations occur in both tasks, with gamma dominating the early odor sampling period (2-4 sniffs) and beta dominating later. The relative power and coherence of both oscillations depend separately on multiple factors within both tasks without categorical differences across tasks. While the early/gamma-associated period occurs in all trials, rats can perform above chance without the later/beta-associated period. Longer sampling, which includes beta oscillations, is associated with better performance. Gamma followed by beta oscillations therefore represents a sequence of cognitive and neural states during odor discrimination, which can be separately modified depending on the demands of a task and odor discrimination. Additionally, fast (85 Hz) and slow (70 Hz) olfactory bulb gamma oscillation sub-bands have been hypothesized to represent tufted and mitral cell networks, respectively (Manabe and Mori, 2013). We find that fast gamma favors the early and slow gamma the later (beta-dominated) odor-sampling period and that the relative contributions of these oscillations are consistent across tasks. SIGNIFICANCE STATEMENT: Olfactory system gamma (40-110 Hz) and beta (15-35 Hz) oscillations of the local field potential indicate different neural firing statistics and functional circuits. We show that gamma and beta oscillations occur in stereotyped sequence during odor sampling in associative tasks, with local gamma dominating the first 250 ms of odor sniffing, followed by systemwide beta as behavioral responses are prepared. Oscillations and coupling strength between brain regions are modulated by task, odor, and learning, showing that task features can dramatically adjust the dynamics of a cortical sensory system, which changes state every ∼250 ms. Understanding cortical circuits, even at the biophysical level, depends on careful use of multiple behavioral contexts and stimuli.

Dual kidney transplants from adult marginal donors successfully expand the limited deceased donor organ pool.

BACKGROUND: The need to expand the organ donor pool remains a formidable challenge in kidney transplantation (KT). The use of expanded criteria donors (ECDs) represents one approach, but kidney discard rates are high because of concerns regarding overall quality. Dual KT (DKT) may reduce organ discard and optimize the use of kidneys from marginal donors. STUDY DESIGN: We conducted a single-center retrospective review of outcomes in adult recipients of DKTs from adult marginal deceased donors (DD) defined by limited renal functional capacity. If the calculated creatinine clearance in an adult DD was <65 mL/min, then the kidneys were transplanted as a DKT. RESULTS: Over 11.5 yr, 72 DKTS were performed including 45 from ECDs, 17 from donation after cardiac death (DCD) donors, and 10 from standard criteria donors (SCD). Mean adult DD and recipient ages were both 60 yr, including 29 DDs and 26 recipients ≥65 yr of age. Mean pre-DKT waiting and dialysis vintage times were 12 months and 25 months, respectively. Actual patient and graft survival rates were 84.7% and 70.8%, respectively, with a mean follow-up of 58 months. One yr and death-censored graft survival rates were 90% and 80%, respectively. Outcomes did not differ by DD category, recipient age, or presence of delayed graft function (DGF). Eleven patients died at a mean of 32 months post-DKT (eight with functioning grafts) and 13 other patients experienced graft losses at a mean of 33 months. The incidence of DGF was 25%; there were two cases (2.8%) of primary non-function. Mean length of initial hospital stay was 7.2 d. Mean serum creatinine and glomerular filtration rate levels at 12 and 24 months were 1.5 and 53 and 1.5 mg/dL and 51 mL/min/1.73 m(2) , respectively. DKT graft survival and function were superior to concurrent single ECD and similar to concurrent SCD KTs. Two patients underwent successful kidney retransplantation, so the dialysis-free rate in surviving patients was 87%. The proportion of total renal function transplanted from adult DD to DKT recipients was 77% compared to 56% for patients receiving single KTs. CONCLUSIONS: Dual kidney transplantation using kidneys from adult marginal DDs that otherwise might be discarded offer a viable option to counteract the growing shortage of acceptable single kidneys. Excellent medium-term outcomes can be achieved and waiting times can be reduced in a predominantly older recipient population.

Influence of recipient age on deceased donor kidney transplant outcomes in the expanded criteria donor era.

METHODS: We performed a retrospective single-center review of 884 deceased donor (DD) kidney transplants (KTs) in patients (pts) aged ≥40 yr. RESULTS: One hundred and four (11.8%) pts were ≥70 (mean 74), 286 (32.3%) were 60-69 (mean 64), and 494 (55.9%) were 40-59 (mean 51) yr of age; the proportion receiving expanded criteria donor (ECD) kidneys were 66%, 49%, and 30%, respectively (p < 0.001). Mean waiting time (15 months) was shorter for pts ≥70 yr compared to the other two groups combined (23 months, p = 0.002). With mean follow-up ranging from 54 to 70 months, actual pt (81% vs. 72%, p = 0.002) and graft (66% vs. 58.5%, p = 0.03) survival rates were higher in the younger compared to the two older groups, whereas death-censored graft survival was similar (76% vs. 73%, p = NS). The incidence of death with a functioning graft correlated with older recipient age group, increasing from 13% to 18% to 23% (p = 0.01). The incidence of delayed graft function was similar (31.8% overall), and renal function, morbidity, and resource utilization were similar among groups. CONCLUSIONS: By directing ECD kidneys to selected older pts, waiting times are reduced and censored survival outcomes are similar to middle-aged patients, suggesting that matching strategies for graft and patient lifespan are warranted.

Single vs dual (en bloc) kidney transplants from donors ≤ 5 years of age: A single center experience.

AIM: To compare outcomes between single and dual en bloc (EB) kidney transplants (KT) from small pediatric donors. METHODS: Monocentric nonprospective review of KTs from pediatric donors ≤ 5 years of age. Dual EB KT was defined as keeping both donor kidneys attached to the inferior vena cava and aorta, which were then used as venous and arterial conduits for the subsequent transplant into a single recipient. Donor age was less useful than either donor weight or kidney size in decision-making for kidney utilization as kidneys from donors < 8 kg or kidneys < 6 cm in length were not transplanted. Post-transplant management strategies were standardized in all patients. RESULTS: From 2002-2015, 59 KTs were performed including 34 dual EB and 25 single KTs. Mean age of donors (17 mo vs 38 mo, P < 0.001), mean weight (11.0 kg vs 17.4 kg, P = 0.046) and male donors (50% vs 84%, P = 0.01) were lower in the dual EB compared to the single KT group, respectively. Mean cold ischemia time (21 h), kidney donor profile index (KDPI; 73% vs 62%) and levels of serum creatinine (SCr, 0.37 mg/dL vs 0.49 mg/dL, all P = NS) were comparable in the dual EB and single KT groups, respectively. Actuarial graft and patient survival rates at 5-years follow-up were comparable. There was one case of thrombosis resulting in graft loss in each group. Delayed graft function incidence (12% dual EB vs 20% single KT, P = NS) was slightly lower in dual EB KT recipients. Initial duration of hospital stay (mean 5.4 d vs 5.6 d) and the one-year incidences of acute rejection (6% vs 16%), operative complications (3% vs 4%), and major infection were comparable in the dual EB and single KT groups, respectively (all P = NS). Mean 12 mo SCr and abbreviated MDRD levels were 1.17 mg/dL vs 1.35 mg/dL and 72.5 mL/min per 1.73 m(2) vs 60.5 mL/min per 1.73 m(2) (both P = NS) in the dual EB and single KT groups, respectively. CONCLUSION: By transplanting kidneys from young pediatric donors into adult recipients, one can effectively expand the limited donor pool and achieve excellent medium-term outcomes.