Neural plasticity is modified over the human menstrual cycle: Combined insight from sensory evoked potential LTP and repetition suppression.

In healthy women, fluctuations in hormones including progesterone and oestradiol lead to functional changes in the brain over the course of each menstrual cycle. Though considerable attention has been directed towards understanding changes in human cognition over the menstrual cycle, changes in underlying processes such as neural plasticity have largely only been studied in animals. In this study we explored predictive coding and repetition suppression via the roving mismatch negativity paradigm as a model of short-term plasticity (Garrido, Kilner, Kiebel, et al., 2009), and Hebbian learning via visual sensory long-term potentiation (LTP) as a model of long-term plasticity (Teyler et al., 2005). Electroencephalography (EEG) was recorded in 20 females during their early follicular and mid-luteal phases. Event-related potential (ERP) analyses were complemented with dynamic causal modelling (DCM) to characterise changes in the underlying neural architecture. More sustained variability in the ERP response to a change in tone during the luteal phase are interpreted as a delayed habituation of the P3a component in the luteal relative to the follicular phase. The additional increased forward connection strength over tone repetitions compared to the follicular phase suggests that, in this phase, females may be less efficient when processing deviations from predicted sensory input (error). In contrast, there appears to be no reliable change in sensory LTP. This suggests that predictive coding, but not Hebbian plasticity is modified in the mid-luteal compared to the follicular phase, at least at the days of the menstrual cycle tested. This finding implicates the human menstrual cycle in complex changes in neural plasticity and provides further evidence for the importance of considering the menstrual cycle when including females in electrophysiological research.

Indexing sensory plasticity: Evidence for distinct Predictive Coding and Hebbian learning mechanisms in the cerebral cortex.

The Roving Mismatch Negativity (MMN), and Visual LTP paradigms are widely used as independent measures of sensory plasticity. However, the paradigms are built upon fundamentally different (and seemingly opposing) models of perceptual learning; namely, Predictive Coding (MMN) and Hebbian plasticity (LTP). The aim of the current study was to compare the generative mechanisms of the MMN and visual LTP, therefore assessing whether Predictive Coding and Hebbian mechanisms co-occur in the brain. Forty participants were presented with both paradigms during EEG recording. Consistent with Predictive Coding and Hebbian predictions, Dynamic Causal Modelling revealed that the generation of the MMN modulates forward and backward connections in the underlying network, while visual LTP only modulates forward connections. These results suggest that both Predictive Coding and Hebbian mechanisms are utilized by the brain under different task demands. This therefore indicates that both tasks provide unique insight into plasticity mechanisms, which has important implications for future studies of aberrant plasticity in clinical populations.

An all oral antiemetic regimen for patients undergoing high-dose chemotherapy with peripheral blood stem cell transplant.

The purpose of the study was to assess the toxicity and efficacy of an oral, combination antiemetic regimen including granisetron (Kytril; SmithKline Beecham Pharmaceuticals, Philadelphia, PA, USA) in the setting of highly emetogenic conditioning chemotherapy for stem cell transplantation. Antiemetic prophylaxis consisted of oral granisetron 2 mg once daily, oral prochlorperazine 10 mg q 6 h and oral dexamethasone 4 mg q 6 h, beginning 1 h prior to chemotherapy on each of the 4 days of chemotherapy and continuing until 24 h after the completion of high-dose chemotherapy (HDC). Patients received either CVP (cyclophosphamide 6 g/m2, VP-16 1800 mg/m2 and carboplatin 1200 mg/m2) or CTP (thiotepa 500 mg/m2 in place of VP-16) in four daily doses given over 4 h from days -4 to -1. Previously mobilized and cryopreserved peripheral blood stem cells (PBSC) were reinfused on day +1. Evaluation of nausea, emetic episodes (EE), adverse events, and rescue medications were recorded on a daily patient diary. Thirty-six patients were entered. Fifty-three percent (95% CI = 37-75%) of patients achieved complete response for emesis (CR = 0 EE/24 h) and 75% (95% CI = 58-90%) had combined complete and major response (CR+MR = 0-3 EE/24 h) during all 5 of the treatment days. During the 5 study days, the average number of patient-days with no emesis was 3.7 (74%) and with 1-3 EE was 4.3 (86%). On days -4, -3, -2, -1 and 0, the combined CR+MR rate for emesis was 97, 92, 86, 78 and 75%, respectively. Nausea was absent or mild on all 5 study days in 57% (95% CI = 37-75%). Eight patients had severe late-onset emesis occurring on days +1 to +3 after reinfusion of stem cells. No clinically significant toxicities attributable to the antiemetic regimen were observed. An all oral antiemetic regimen of granisetron, prochlorperazine and dexamethasone appears to be safe and highly effective in patients receiving multiple, daily, high-dose chemotherapy regimens. This regimen offers the advantage of cost-savings, a low side-effect profile and ease of administration in the predominately outpatient setting of HDC with peripheral blood stem cell transplant (PBSCT).