Cortical free association dynamics: distinct phases of a latching network

A Potts associative memory network has been proposed as a simplified model of macroscopic cortical dynamics, in which each Potts unit stands for a patch of cortex, which can be activated in one of S local attractor states. The internal neuronal dynamics of the patch is not described by the model, rather it is subsumed into an effective description in terms of graded Potts units, with adaptation effects both specific to each attractor state and generic to the patch. If each unit, or patch, receives effective (tensor) connections from C other units, the network has been shown to be able to store a large number p of global patterns, or network attractors, each with a fraction a of the units active, where the critical load p_c scales roughly like p_c ~ (C S^2)/(a ln(1/a)) (if the patterns are randomly correlated). Interestingly, after retrieving an externally cued attractor, the network can continue jumping, or latching, from attractor to attractor, driven by adaptation effects. The occurrence and duration of latching dynamics is found through simulations to depend critically on the strength of local attractor states, expressed in the Potts model by a parameter w. Here we describe with simulations and then analytically the boundaries between distinct phases of no latching, of transient and sustained latching, deriving a phase diagram in the plane w-T, where T parametrizes thermal noise effects. Implications for real cortical dynamics are briefly reviewed in the conclusions

Dinamica di Latching in una Memoria Associativa di Potts

Scopo di questo lavoro di tesi e' costruire un modello di rete neurale che mimi il comportamento della corteccia cerebrale in due particolari processi cognitivi: il processo di riconoscimento, ovvero come le informazioni memorizzate vengano recuperate a seguito della presentazione di uno stimolo esterno, e il processo di latching, ovvero lo spontaneo passaggio da una memoria ad un'altra ad essa correlata. La modellizazione di questi processi si basa sulla descrizione della corteccia in termini di rete neurale e sfrutta il formalismo del modello di Ising. In questi termini la rete diventa una memoria associativa e un 'concetto' coincide con una particolare configurazione della rete (pattern). Punto di partenza e' il modello classico di Hopfield, modificato di volta in volta secondo due criteri guida fondamentali: da un lato le caratteristiche strutturali biologiche del sistema considerato, la corteccia, dall'altro l'esigenza di descrivere non solo il recupero di un concetto all'interno della rete, ma anche il fenomeno di passaggio spontaneo da un concetto all'altro. Rispettivamente, i vincoli legati alla struttura biologica portano all'utilizzo del modello di Potts, mentre il fenomeno di passaggio, o latching, comporta l'introduzione di patterns correlati e di un complesso meccanismo di adattamento della rete. Sono stati prodotti dunque quattro modelli, evoluti uno dall'altro. Per ognuno dei essi e' stata sviluppata una simulazione numerica e una derivazione teorica delle equazioni della dinamica. Il modello finale consiste in una rete di Potts in grado di recuperare un pattern tra i memorizzati e da questo passare spontaneamente ad un altro ad esso correlato. Il motivo che ci ha spinto allo studio di tale processo e' legato alla possibilita' che questo rappresenti l'unita' di base nel fenomeno che noi percepiamo come susseguirsi di pensieri

Growth mechanisms of III-V semiconductor nanostructures on silicon

The aim of this thesis is to understand the dynamics of the growth of catalyst-free III-V semiconductor nanostructures on silicon substrates, focusing the attention mainly on the early stages of growths. A detailed understanding of this first phase of the process is a key step to obtain a completely successful integration of highly functional materials, like the III-Vs, on the CMOS platform, and to synthesize nanostructures with tailored properties. Indeed, the first mandatory step in nanotechnology is the possibility to fabricate nanostructures and nanomaterials, i.e. structures and materials with at least one dimension falling in the nanometer scale. Among different nanostructures, semiconductor nanowires (NWs) have proven to be versatile building blocks for a manifold of applications. In this work two types of nanostructures have been investigated: NWs and V-shaped nanomembranes. Their growth has been performed by molecular beam epitaxy (MBE), a technique that allows to produce ultrapure nanostructures, with very high crystalline quality and atomically sharp interfaces. The growth has been obtained with a self-catalyzed approach, meaning that no external material, apart the constituents of the semiconductor to be grown, has been used. This allows to avoid any possible contamination of the substrate, a fundamental requirement to ensure a full compatibility with the silicon technology. We performed a systematic study on the growth directions of self-catalyzed GaAs NWs grown on silicon substrates. Indeed, when growing III-V NWs on silicon non vertical wires always appear. In order to make NW-based structures on silicon effective for applications like energy harvesting (one of the most promising so far) it is mandatory to control the growth direction and in particular to maximize the yield of NWs perpendicular to the surface. By analyzing the first stages of growth we shed light on the mechanism responsible for the different NWs orientations: we optimized the growth conditions to obtain up to a 100% yield of vertical NWs. Having attained growth of nanostructures in an ordered manner along regular arrays is a subsequent step for the fabrication of devices. In this work our capability to control growth of InAs and GaAs NWs in arrays is presented and the existing challenges for the reproducible growth are highlighted. Lastly, we turned to the growth of nanostructures on exactly oriented (001) substrates, which would make the III-V/group IV integration compatible with the current technological pro- cesses. This led us to the discovery of a new class of III-V semiconductor nanostructures, called V-shaped nanomembranes, characterized by a unique morphology and growth mech- anism and possessing interesting optical properties. An accurate characterization of their morphology and a complete understanding of their nucleation and growth mechanism is reported. These results give a clear pathway of how to obtain fully controlled structures which as such could be useful for the realization of complex branched interconnected nanoelectronic devices

Free association transitions in models of cortical latching dynamics

Potts networks, in certain conditions, hop spontaneously from one discrete attractor state to another, a process we have called latching dynamics. When continuing indefinitely, latching can serve as a model of infinite recursion, which is nontrivial if the matrix of transition probabilities presents a structure, i.e. a rudimentary grammar. We show here, with computer simulations, that latching transitions cluster in a number of distinct classes: effectively random transitions between weakly correlated attractors; structured, history-dependent transitions between attractors with intermediate correlations; and oscillations between pairs of closely overlapping attractors. Each type can be described by a reduced set of equations of motion, which, once numerically integrated, matches simulations results. We propose that the analysis of such equations may offer clues on how to embed meaningful grammatical structures into more realistic models of specific recursive processes

Diabete Mellito Tipo 1 e Nefropatia Diabetica: Nuovi Profili Fenotipici di Malattia Renale Cronica

La malattia renale cronica (Chronic Kidney Disease, CKD) rappresenta una delle principali complicanze del diabete mellito (DM) ed un fattore di rischio cardiovascolare indipendente. Nel DM tipo 2 studi recenti dimostrano che aumento dell’albuminuria e riduzione della funzione renale (glomerular filtration rate, GFR), i due marker fondamentali di stratificazione della CKD, possono intervenire indipendentemente l’uno dall’altro. E’ così possibile che macroalbuminuria compaia in soggetti con normale GFR e, viceversa, che riduzioni del GFR possano intervenire in assenza di albuminuria. Insiemi distinti di fattori di rischio sono associati allo sviluppo di albuminuria e ridotta funzione renale in armonia con l’ipotesi che le due condizioni non siano inevitabilmente tra loro associate. Inoltre, elevata albuminuria e ridotto GFR sono fattori di rischio indipendenti per eventi cardiovascolari (CVD) e renali (End Stage Renal Disease, ESRD). Queste osservazioni depongono per una visione bi-dimensionale della nefropatia nel diabete in cui l’evoluzione spesso indipendente dei due parametri che descrivono la progressione del danno renale, identifica fenotipi eterogenei che possono progredire in maniera distinta. Anche nel DM tipo 1 (DMT1), come dimostrato dal Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC), una riduzione del GFR (<60 ml/min/1,73 m2) indicativa di danno renale può avvenire in assenza di albuminuria. In questo studio, infatti, il 24% dei soggetti avrebbe sviluppato riduzione del GFR in assenza di albuminuria. In questo contesto, scopo dello studio è stato quello di valutare prevalenza e caratteristiche cliniche dei vari fenotipi di malattia renale cronica che è possibile identificare tra i soggetti con diabete mellito tipo 1. Con questo obiettivo sono state studiate due ampie coorti di pazienti con DMT1. La prima coorte è rappresentata da 777 pazienti con DMT1 afferiti negli anni 2001-2009 all’Unità Operativa di Malattie Metaboliche e Diabetologia dell’Azienda Ospedaliero Universitaria di Pisa per eseguire lo screening delle complicanze croniche del diabete. La seconda coorte è rappresentata da 936 pazienti con DMT1 arruolati nell’EURODIAB Complications Study. Nella prima coorte (777 DMT1), il 91.6% dei soggetti presentava normoalbuminuria, il 6.4% micro- ed l’1.9% macro-albuminuria. Il 57.3% aveva eGFR ≥90 ml/min/1,73 m2, il 39.0% eGFR 60-89 ml/min/1,73 m2, il 3.6% eGFR 30-59 ml/min/1,73 m2 e lo 0.1% eGFR <30 ml/min/1,73 m2. L’89.4% dei pazienti non presentava CKD, mentre CKD di stadio 1, 2 e 3-5 era presente rispettivamente nel 4.0%, 2.8% e 3.7% dei soggetti. Eventi cardiovascolari sono stati registrati soltanto nel 7.2% dei soggetti senza CKD rispetto al 22.7% e 34.5% dei soggetti con CKD stadio 2 e CKD stadi 3-5 (p<0.0001). Tra i pazienti con eGFR <60 ml/min/1,73 m2, il 59% presentava normale escrezione urinaria di albumina. Analogamente, normale escrezione urinaria di albumina era presente nel 88.7% dei soggetti con eGFR compreso tra 60 e 74 ml/min/1,73 m2. L’eterogeneità dei fenotipi di CKD è stata confermata dai risultati ottenuti nella seconda coorte (936 DMT1 reclutati nello studio EURODIAB). In conclusione, analogamente a quanto osservato nel DMT2, il fenotipo normoalbuminurico di malattia renale cronica si manifesta in una significativa percentuale di pazienti con DMT1. I risultati dello studio sostengono quindi l’ipotesi di due distinte “pathways”, una albuminurica e l’altra non-albuminurica, nella progressione del danno renale verso l’ESRD e la patologia cardiovascolare

Non-destructive techniques for structural characterization of cultural heritage: A pilot case study

n/

Correlation between oesophageal acid exposure and dyspeptic symptoms in patients with nonerosive reflux disease.

Oesophageal acidification induces dyspeptic symptoms in healthy individuals. This study aimed to evaluate the correlation between oesophageal acid exposure and dyspeptic symptoms in patients with nonerosive reflux disease. METHODS: A total of 68 patients with dominant symptoms of heartburn, negative upper gastrointestinal endoscopy and concomitant dyspeptic symptoms participated in the study. The severity of dyspepsia and reflux-related symptoms was evaluated, and 24-h gastro-oesophageal pH-monitoring study was performed in all patients at baseline and after 4 weeks of therapy with esomeprazole 40 mg. RESULTS: Oesophageal basal acid exposure was pathological in 43 patients and normal in 25 patients, with a similar prevalence and severity of individual dyspeptic symptoms in the two groups. A significant correlation between reflux and dyspepsia scores was observed in the subgroup of patients with normal, but not in those with abnormal pHmetry (r=0.4, P=0.04 and r=0.2 P=0.07, respectively). After esomeprazole, a reduction in severity of dyspepsia (>or=50% with respect to baseline) was observed, independent of improvement of reflux-associated symptoms. Improvement in dyspepsia was, however, similar in patients with normal and abnormal basal acid exposure (14/25 vs. 33/43, respectively, P=NS). CONCLUSION: Dyspeptic symptoms coexist in a subset of nonerosive reflux disease patients, but prevalence and severity of the symptoms seems to be independent of oesophageal acid exposure

Amygdala Corticofugal Input Shapes Mitral Cell Responses in the Accessory Olfactory Bulb

Interconnections between the olfactory bulb and the amygdala are a major pathway for triggering strong behavioral responses to a variety of odorants. However, while this broad mapping has been established, the patterns of amygdala feedback connectivity and the influence on olfactory circuitry remain unknown. Here, using a combination of neuronal tracing approaches, we dissect the connectivity of a cortical amygdala [posteromedial cortical nucleus (PmCo)] feedback circuit innervating the mouse accessory olfactory bulb. Optogenetic activation of PmCo feedback mainly results in feedforward mitral cell (MC) inhibition through direct excitation of GABAergic granule cells. In addition, LED-driven activity of corticofugal afferents increases the gain of MC responses to olfactory nerve stimulation. Thus, through corticofugal pathways, the PmCo likely regulates primary olfactory and social odor processing

Connecting the dots in the zona incerta: A study of neural assemblies and motifs of inter-area coordination in mice

The zona incerta (ZI), a subthalamic area connected to numerous brain regions, has raised clinical interest because its stimulation alleviates the motor symptoms of Parkinson’s disease. To explore its coordinative nature, we studied the assembly formation in a dataset of neural recordings in mice and quantified the degree of functional coordination of ZI with other 24 brain areas. We found that the ZI is a highly integrative area. The analysis in terms of “loop-like” motifs, directional assemblies composed of three neurons spanning two areas, has revealed reciprocal functional interactions with reentrant signals that, in most cases, start and end with the activation of ZI units. In support of its proposed integrative role, we found that almost one-third of the ZI’s neurons formed assemblies with more than half of the other recorded areas and that loop-like assemblies may stand out as hyper-integrative motifs compared to other types of activation patterns