Associative learning of classical conditioning as an emergent property of spatially extended spiking neural circuits with synaptic plasticity.

Associative learning of temporally disparate events is of fundamental importance for perceptual and cognitive functions. Previous studies of the neural mechanisms of such association have been mainly focused on individual neurons or synapses, often with an assumption that there is persistent neural firing activity that decays slowly. However, experimental evidence supporting such firing activity for associative learning is still inconclusive. Here we present a novel, alternative account of associative learning in the context of classical conditioning, demonstrating that it is an emergent property of a spatially extended, spiking neural circuit with spike-timing dependent plasticity and short term synaptic depression. We show that both the conditioned and unconditioned stimuli can be represented by spike sequences which are produced by wave patterns propagating through the network, and that the interactions of these sequences are timing-dependent. After training, the occurrence of the sequence encoding the conditioned stimulus (CS) naturally regenerates that encoding the unconditioned stimulus (US), therefore resulting in association between them. Such associative learning based on interactions of spike sequences can happen even when the timescale of their separation is significantly larger than that of individual neurons. In particular, our network model is able to account for the temporal contiguity property of classical conditioning, as observed in behavioral studies. We further show that this emergent associative learning in our network model is quite robust to noise perturbations. Our results therefore demonstrate that associative learning of temporally disparate events can happen in a distributed way at the level of neural circuits.

Formation and regulation of dynamic patterns in two-dimensional spiking neural circuits with spike-timing-dependent plasticity.

Spike-timing-dependent plasticity (STDP) is an important synaptic dynamics that is capable of shaping the complex spatiotemporal activity of neural circuits. In this study, we examine the effects of STDP on the spatiotemporal patterns of a spatially extended, two-dimensional spiking neural circuit. We show that STDP can promote the formation of multiple, localized spiking wave patterns or multiple spike timing sequences in a broad parameter space of the neural circuit. Furthermore, we illustrate that the formation of these dynamic patterns is due to the interaction between the dynamics of ongoing patterns in the neural circuit and STDP. This interaction is analyzed by developing a simple model able to capture its essential dynamics, which give rise to symmetry breaking. This occurs in a fundamentally self-organizing manner, without fine-tuning of the system parameters. Moreover, we find that STDP provides a synaptic mechanism to learn the paths taken by spiking waves and modulate the dynamics of their interactions, enabling them to be regulated. This regulation mechanism has error-correcting properties. Our results therefore highlight the important roles played by STDP in facilitating the formation and regulation of spiking wave patterns that may have crucial functional roles in brain information processing.

Fate of the leftover bladder after supravesical urinary diversion for benign disease.

PURPOSE: We studied the fate of the leftover bladder in patients who underwent supravesical urinary diversion without cystectomy for benign pathology. MATERIALS AND METHODS: This retrospective study was performed in 9 males and 15 females with a median age of 59 years in whom supravesical urinary diversion was performed for various benign conditions from 1996 to 2004. These conditions were incontinence, acontractile bladder, radiation and/or hemorrhagic cystitis, and neuropathic bladder. Median followup was 48 months. RESULTS: Of the patients 13 (54%) experienced problems with the retained bladder, 2 (8%) presented with urethral bleeding, which resolved by conservative means, and 11 (46%) had infective complications, which resolved with expectant treatment in 3 (12%). However, 8 patients (33%) had frank pyocystis and 3 (12%) were treated with the Spence procedure, which alleviated symptoms in only 1. Six patients (25%) required cystectomy. CONCLUSIONS: In patients undergoing supravesical urinary diversion for benign disease in whom the bladder remains in situ the risks of complications related to the defunctionalized bladder are more than 50% and 25% of patients subsequently need cystectomy. These patients should be offered primary cystectomy at urinary diversion.

The 12-year outcome analysis of an endourethral wallstent for treating benign prostatic hyperplasia.

OBJECTIVE: To evaluate the long-term results of using the Urolume(TM) endourethral prosthesis (American Medical Systems, Minnetonka, MN, USA) for managing benign prostatic hyperplasia (BPH), an alternative minimally invasive option. PATIENTS AND METHODS: Sixty-two patients with moderate/severe lower urinary tract symptoms secondary to BPH were treated with the Urolume stent by one surgeon (J.H.P.). They were followed up at 12 weeks, 6 months and then yearly. Data recorded before and after treatment included symptom scoring, peak urinary flow rate (PFR) and postvoid residual volume (PVR). A one-way anova was used to compare baseline and the 5- and 12-year follow-up data. RESULT: Twenty-two and 11 patients completed the 5- and 12-year follow-up, respectively. Twenty-one (34%) patients died with the stent in situ from causes unrelated to BPH and Urolume insertion. Twenty-nine (47%) stents were removed; 18 in the first 2 years, seven at 3-5 years and four at 9-10 years. Early stent explantation was primarily a result of poor case selection, or stent malposition/migration. Four stents were removed because the patient was dissatisfied. Late stent explantation was for symptom progression. At 5 years, the symptom score and PFR were 6.82 an 11.7 mL/s, respectively, compared with 20.4 and 9 mL/s at basleine (P < 0.05); at 12 years, the symptom score, PFR and PVR were 10.82, 11.5 mL/s and 80 mL, respectively. The mean quality of life score was 2 and no patient opted for any further treatment. CONCLUSION: The Urolume wallstent is a safe treatment for BPH, in selected patients. Careful case selection and experience is mandatory. This stent can provide the urologist with an alternative along with other minimally invasive treatments for men with BPH at high risk of requiring transurethral resection.