Nonlinear estimation of neural processing time from BOLD signal with application to decision-making

The extraction of information about neural activity timing from BOLD signal is a challenging task as the shape of the BOLD curve does not directly reflect the temporal characteristics of electrical activity of neurons. In this work, we introduce the concept of neural processing time (NPT) as a parameter of the biophysical model of the hemodynamic response function (HRF). Through this new concept we aim to infer more accurately the duration of neuronal response from the highly nonlinear BOLD effect. The face validity and applicability of the concept of NPT are evaluated through simulations and analysis of experimental time series. The results of both simulation and application were compared with summary measures of HRF shape. The experiment that was analyzed consisted of a decision-making paradigm with simultaneous emotional distracters. We hypothesize that the NPT in primary sensory areas, like the fusiform gyrus, is approximately the stimulus presentation duration. On the other hand, in areas related to processing of an emotional distracter, the NPT should depend on the experimental condition. As predicted, the NPT in fusiform gyrus is close to the stimulus duration and the NPT in dorsal anterior cingulate gyrus depends on the presence of an emotional distracter. Interestingly, the NPT in right but not left dorsal lateral prefrontal cortex depends on the stimulus emotional content. The summary measures of HRF obtained by a standard approach did not detect the variations observed in the NPT. Hum Brain Mapp, 2012. (C) 2010 Wiley Periodicals, Inc.

Cortical activation during executed, imagined, observed, and passive wrist movements in healthy volunteers and stroke patients

Motor imagery, passive movement, and movement observation have been suggested to activate the sensorimotor system without overt movement. The present study investigated these three covert movement modes together with overt movement in a within-subject design to allow for a fine-grained comparison of their abilities in activating the sensorimotor system, i.e. premotor, primary motor, and somatosensory cortices. For this, 21 healthy volunteers underwent functional magnetic resonance imaging (fMRI). In addition we explored the abilities of the different covert movement modes in activating the sensorimotor system in a pilot study of 5 stroke patients suffering from chronic severe hemiparesis. Results demonstrated that while all covert movement modes activated sensorimotor areas, there were profound differences between modes and between healthy volunteers and patients. In healthy volunteers, the pattern of neural activation in overt execution was best resembled by passive movement, followed by motor imagery, and lastly by movement observation. In patients, attempted overt execution was best resembled by motor imagery, followed by passive movement and lastly by movement observation. Our results indicate that for severely hemiparetic stroke patients motor imagery may be the preferred way to activate the sensorimotor system without overt behavior. In addition, the clear differences between the covert movement modes point to the need for within-subject comparisons. (C) 2012 Elsevier Inc. All rights reserved.

Meditation training increases brain efficiency in an attention task

Meditation is a mental training, which involves attention and the ability to maintain focus on a particular object. In this study we have applied a specific attentional task to simply measure the performance of the participants with different levels of meditation experience, rather than evaluating meditation practice per se or task performance during meditation. Our objective was to evaluate the performance of regular meditators and non-meditators during an fMRI adapted Stroop Word-Colour Task (SWCT), which requires attention and impulse control, using a block design paradigm. We selected 20 right-handed regular meditators and 19 non-meditators matched for age, years of education and gender. Participants had to choose the colour (red, blue or green) of single words presented visually in three conditions: congruent, neutral and incongruent. Non-meditators showed greater activity than meditators in the right medial frontal, middle temporal, precentral and postcentral gyri and the lentiform nucleus during the incongruent conditions. No regions were more activated in meditators relative to non-meditators in the same comparison. Non-meditators showed an increased pattern of brain activation relative to regular meditators under the same behavioural performance level. This suggests that meditation training improves efficiency, possibly via improved sustained attention and impulse control. (C) 2011 Elsevier Inc. All rights reserved.

Functional Magnetic Resonance Imaging Data Analysis by Autoregressive Estimator

The autoregressive (AR) estimator, a non-parametric method, is used to analyze functional magnetic resonance imaging (fMRI) data. The same method has been used, with success, in several other time series data analysis. It uses exclusively the available experimental data points to estimate the most plausible power spectra compatible with the experimental data and there is no need to make any assumption about non-measured points. The time series, obtained from fMRI block paradigm data, is analyzed by the AR method to determine the brain active regions involved in the processing of a given stimulus. This method is considerably more reliable than the fast Fourier transform or the parametric methods. The time series corresponding to each image pixel is analyzed using the AR estimator and the corresponding poles are obtained. The pole distribution gives the shape of power spectra, and the pixels with poles at the stimulation frequency are considered as the active regions. The method was applied in simulated and real data, its superiority is shown by the receiver operating characteristic curves which were obtained using the simulated data.

A graph-theoretical approach in brain functional networks. Possible implications in EEG studies

Abstract Background Recently, it was realized that the functional connectivity networks estimated from actual brain-imaging technologies (MEG, fMRI and EEG) can be analyzed by means of the graph theory, that is a mathematical representation of a network, which is essentially reduced to nodes and connections between them. Methods We used high-resolution EEG technology to enhance the poor spatial information of the EEG activity on the scalp and it gives a measure of the electrical activity on the cortical surface. Afterwards, we used the Directed Transfer Function (DTF) that is a multivariate spectral measure for the estimation of the directional influences between any given pair of channels in a multivariate dataset. Finally, a graph theoretical approach was used to model the brain networks as graphs. These methods were used to analyze the structure of cortical connectivity during the attempt to move a paralyzed limb in a group (N=5) of spinal cord injured patients and during the movement execution in a group (N=5) of healthy subjects. Results Analysis performed on the cortical networks estimated from the group of normal and SCI patients revealed that both groups present few nodes with a high out-degree value (i.e. outgoing links). This property is valid in the networks estimated for all the frequency bands investigated. In particular, cingulate motor areas (CMAs) ROIs act as ‘‘hubs’’ for the outflow of information in both groups, SCI and healthy. Results also suggest that spinal cord injuries affect the functional architecture of the cortical network sub-serving the volition of motor acts mainly in its local feature property. In particular, a higher local efficiency El can be observed in the SCI patients for three frequency bands, theta (3-6 Hz), alpha (7-12 Hz) and beta (13-29 Hz). By taking into account all the possible pathways between different ROI couples, we were able to separate clearly the network properties of the SCI group from the CTRL group. In particular, we report a sort of compensatory mechanism in the SCI patients for the Theta (3-6 Hz) frequency band, indicating a higher level of “activation” Ω within the cortical network during the motor task. The activation index is directly related to diffusion, a type of dynamics that underlies several biological systems including possible spreading of neuronal activation across several cortical regions. Conclusions The present study aims at demonstrating the possible applications of graph theoretical approaches in the analyses of brain functional connectivity from EEG signals. In particular, the methodological aspects of the i) cortical activity from scalp EEG signals, ii) functional connectivity estimations iii) graph theoretical indexes are emphasized in the present paper to show their impact in a real application.

The biopsychosocial processes in autism spectrum disorder

Abstract Background Autism is a disorder characterized by pervasive social and communicative impairments, repetitive and stereotyped behaviors and restricted interests. Its causes and effects have been researched from various neurocognitive theoretical perspectives and with the aid of neuroimaging technology. We aimed to describe biopsychosocial processes characteristic of the Autism Spectrum Disorders. Method Literature review using Medline and Scopus databases published between 2001 and 2011, with the keywords "autism", "theory of mind", "executive functions", "central coherence" and “fMRI”. Results The studies found were plotted and organized into tables and an explanatory diagram of the main findings was produced. Conclusions The most popular neurocognitive theories are still unable to fully explain the characteristics of the complications that autistic spectrum disorder causes to the quality of life of individuals living with autism. The association of clinical research and neuroimaging may contribute to a better understanding of the functioning of the brain affected by the disorder.

Neuroimaging in specific phobia disorder: a systematic review of the literature

OBJECTIVE: Specific phobia (SP) is characterized by irrational fear associated with avoidance of specific stimuli. In recent years, neuroimaging techniques have been used in an attempt to better understand the neurobiology of anxiety disorders. The objective of this study was to perform a systematic review of articles that used neuroimaging techniques to study SP. METHOD:A literature search was conducted through electronic databases, using the keywords: imaging, neuroimaging, PET, spectroscopy, functional magnetic resonance, structural magnetic resonance, SPECT, MRI, DTI, and tractography, combined with simple phobia and specific phobia. One-hundred fifteen articles were found, of which 38 were selected for the present review. From these, 24 used fMRI, 11 used PET, 1 used SPECT, 2 used structural MRI, and none used spectroscopy. RESULT: The search showed that studies in this area were published recently and that the neuroanatomic substrate of SP has not yet been consolidated. CONCLUSION: In spite of methodological differences among studies, results converge to a greater activation in the insula, anterior cingulate cortex, amygdala, and prefrontal and orbitofrontal cortex of patients exposed to phobia-related situations compared to controls. These findings support the hypotheses of the hyperactivation of a neuroanatomic structural network involved in SP.

Applicazione della neurodiagnostica avanzata allo studio dei disturbi psicologici nelle malattie infiammatorie croniche intestinali

Background and aim Ulcerative Colitis (UC) and Crohn’s Disease (CD), collectively labelled as inflammatory bowel disease (IBD), are idiopathic, chronic inflammatory disorder of the bowel with a remitting and relapsing course. IBD are associated to poor emotional functioning and psychological distress. We have investigated the brain involvement in patients with IBD using functional magnetic resonance imaging (fMRI). Materials and methods We developed an emotional visual task to investigate the emotional functioning in 10 UC patients and 10 healthy controls (HC). Furthermore, we have compared the brain stress response between a group of 20 CD patients and a group of 18 HC. Finally, we evaluated potential morphological differences between 18 CD patients and 18 HC in a voxel based morphometry (VBM) study. Results We found brain functional changes in UC patients characterized by decreased activity in the amygdala in response to positive emotional stimuli. Moreover, in CD patients, the brain stress response and habituation to stressful stimuli were significantly different in the medial temporal lobe (including the amygdala and hippocampus), the insula and cerebellum. Finally, in CD patients there were morphological abnormalities in the anterior mid cingulated cortex (aMCC). Conclusion IBD are associated to functional and morphological brain abnormalities. The previous intestinal inflammatory activity in IBD patients might have contributed to determine the functional and morphological changes we found. On the other hand, the dysfunctions of the brain structures we found may influence the course of the disease. Our findings might have clinical implications. The differences in the emotional processing may play a role in the development of psychological disorders in UC patients. Furthermore, in CD patients, the different habituation to stress might contribute to stress related inflammatory exacerbations. Finally, the structural changes in the aMCC might be involved in the pain symptoms associated to the bowel disorder.

Heterogeneous multicore systems for signal processing

This thesis explores the capabilities of heterogeneous multi-core systems, based on multiple Graphics Processing Units (GPUs) in a standard desktop framework. Multi-GPU accelerated desk side computers are an appealing alternative to other high performance computing (HPC) systems: being composed of commodity hardware components fabricated in large quantities, their price-performance ratio is unparalleled in the world of high performance computing. Essentially bringing “supercomputing to the masses”, this opens up new possibilities for application fields where investing in HPC resources had been considered unfeasible before. One of these is the field of bioelectrical imaging, a class of medical imaging technologies that occupy a low-cost niche next to million-dollar systems like functional Magnetic Resonance Imaging (fMRI). In the scope of this work, several computational challenges encountered in bioelectrical imaging are tackled with this new kind of computing resource, striving to help these methods approach their true potential. Specifically, the following main contributions were made: Firstly, a novel dual-GPU implementation of parallel triangular matrix inversion (TMI) is presented, addressing an crucial kernel in computation of multi-mesh head models of encephalographic (EEG) source localization. This includes not only a highly efficient implementation of the routine itself achieving excellent speedups versus an optimized CPU implementation, but also a novel GPU-friendly compressed storage scheme for triangular matrices. Secondly, a scalable multi-GPU solver for non-hermitian linear systems was implemented. It is integrated into a simulation environment for electrical impedance tomography (EIT) that requires frequent solution of complex systems with millions of unknowns, a task that this solution can perform within seconds. In terms of computational throughput, it outperforms not only an highly optimized multi-CPU reference, but related GPU-based work as well. Finally, a GPU-accelerated graphical EEG real-time source localization software was implemented. Thanks to acceleration, it can meet real-time requirements in unpreceeded anatomical detail running more complex localization algorithms. Additionally, a novel implementation to extract anatomical priors from static Magnetic Resonance (MR) scansions has been included.

Funktionelle Magnetresonanztomographie mittels simultaner EEG-Registrierung interiktaler Spikes bei fokaler Epilepsie: Vergleich der on-, off- mit der häufigkeitskorrelierten Datenanalyse

Obwohl die funktionelle Magnetresonanztomographie (fMRI) interiktaler Spikes mit simultaner EEG-Ableitung bei Patienten mit fokalen Anfallsleiden seit einigen Jahren zur Lokalisation beteiligter Hirnstrukturen untersucht wird, ist sie nach wie vor eine experimentelle Methode. Um zuverlässig Ergebnisse zu erhalten, ist insbesondere die Verbesserung des Signal-zu-Rausch-Verhältnisses in der statistischen Bilddatenauswertung von Bedeutung. Frühere Untersuchungen zur sog. event-related fMRI weisen auf einen Zusammenhang zwischen Häufigkeit von Einzelreizen und nachfolgender hämodynamischer Signalantwort in der fMRI hin. Um einen möglichen Einfluss der Häufigkeit interiktaler Spikes auf die Signalantwort nachzuweisen, wurden 20 Kinder mit fokaler Epilepsie mit der EEG-fMRI untersucht. Von 11 dieser Patienten konnten die Daten ausgewertet werden. In einer zweifachen Analyse mit dem Softwarepaket SPM99 wurden die Bilddaten zuerst ausschließlich je nach Auftreten interiktaler Spikes der „Reiz“- oder „Ruhe“-Bedingung zugeordnet, unabhängig von der jeweiligen Anzahl der Spikes je Messzeitpunkt (on/off-Analyse). In einem zweiten Schritt wurden die „Reiz“- Bedingungen auch differenziert nach jeweiliger Anzahl einzelner Spikes ausgewertet (häufigkeitskorrelierte Analyse). Die Ergebnisse dieser Analysen zeigten bei 5 der 11 Patienten eine Zunahme von Sensitivität und Signifikanzen der in der fMRI nachgewiesenen Aktivierungen. Eine höhere Spezifität konnte hingegen nicht gezeigt werden. Diese Ergebnisse weisen auf eine positive Korrelation von Reizhäufigkeit und nachfolgender hämodynamischer Antwort auch bei interiktalen Spikes hin, welche für die EEG-fMRI nutzbar ist. Bei 6 Patienten konnte keine fMRI-Aktivierung nachgewiesen werden. Mögliche technische und physiologische Ursachen hierfür werden diskutiert.

Neuroökonomie = (Neuroeconomics): Neuronale Mechanismen ökonomischer Entscheidungen

Ökonomische Entscheidungen sind ebenso wie alltägliche Entscheidungen von der Aktivität von Hirnregionen abhängig, die zur Kontrolle verschiedener Teilschritte der Entscheidung beitragen. Aktivierung und Desaktivierung dieser Hirnregionen können mit Hilfe moderner bildgebender Verfahren, wie z.B. der funktionellen Magnet-Resonanz-Tomographie (fMRI) dargestellt werden. Die vorliegende Publikation gibt einen Überblick über das interdisziplinäre wissenschaftliche Arbeitsgebiet der „Neuroökonomie“ – einem jungen Forschungsfeld der Neurowissenschaften. Dieser Überblick ist auf sieben Hauptaspekte ökonomischer und finanzieller Entscheidungen fokusiert: 1. In welcher Weise werden ökonomische Parameter wie Wert und Nutzen einer Belohnung, Gewinn oder Verlust, Risiko und Ungewissheit in spezifischen Hirnregionen abgebildet? 2. In welcher spezifischen Weise tragen anatomisch definierte Areale des Gehirns zum Entscheidungsprozess bei? 3. In welcher Weise sind die Entscheidungsprozesse durch Läsion entscheidungsrelevanter Areale des Gehirns gestört? 4. In welcher Weise sind Hirnregionen, die an den Prozessen der Entscheidung beteiligt sind, miteinander vernetzt, um durch Interaktion die Entscheidung herbeizuführen? 5. In welcher Weise ist der Entscheidungsprozess von Persönlichkeitseigenschaften, von genetischen Variationen neuronaler Funktionen und von physiologischer Regulation, z.B. durch Hormone bestimmt? 6. In welcher Weise hängt der Entscheidungsprozess vom sozialen und kulturellen Umfeld des Entscheiders ab? 7. Auf welche Weise werden bei unvollständiger Information über die Optionen der Entscheidung Heuristiken oder Intuitionen genutzt, und in welcher Weise sind Entscheidungen durch Biases beeinflussbar? Der zentrale Teil dieser Publikation gibt einen zusammenfassenden Überblick (review) über die Ergebnisse neuroökonomischer Studien, die die fMRI-Technik nutzen (bis Juni 2010).

The posterior parietal cortex: a bridge between vision and action

The present work takes into account three posterior parietal areas, V6, V6A, and PEc, all operating on different subsets of signals (visual, somatic, motor). The work focuses on the study of their functional properties, to better understand their respective contribution in the neuronal circuits that make possible the interactions between subject and external environment. In the caudalmost pole of parietal lobe there is area V6. Functional data suggest that this area is related to the encoding of both objects motion and ego-motion. However, the sensitivity of V6 neurons to optic flow stimulations has been tested only in human fMRI experiments. Here we addressed this issue by applying on monkey the same experimental protocol used in human studies. The visual stimulation obtained with the Flow Fields stimulus was the most effective and powerful to activate area V6 in monkey, further strengthening this homology between the two primates. The neighboring areas, V6A and PEc, show different cytoarchitecture and connectivity profiles, but are both involved in the control of reaches. We studied the sensory responses present in these areas, and directly compared these.. We also studied the motor related discharges of PEc neurons during reaching movements in 3D space comparing also the direction and depth tuning of PEc cells with those of V6A. The results show that area PEc and V6A share several functional properties. Area PEc, unlike V6A, contains a richer and more complex somatosensory input, and a poorer, although complex visual one. Differences emerged also comparing the motor-related properties for reaches in depth: the incidence of depth modulations in PEc and the temporal pattern of modulation for depth and direction allow to delineate a trend among the two parietal visuomotor areas.

Approccio strumentale per l'acquisizione del segnale epilettico

L’epilessia è una patologia neurologica cronica caratterizzata dalla tendenza, in un dato soggetto, a generare crisi convulsive spontanee, accompagnate generalmente da perdita di coscienza. Rappresenta uno fra i più frequenti disturbi neurologici cronici: l’1% della popolazione mondiale (circa 50 milioni) ne è affetta. Il presente elaborato di tesi ha analizzato le tecniche di imaging biomediche non invasive per lo studio dell’epilessia. Le tecniche PET, MEG e fMRI contribuiscono non solo a fornire una migliore comprensione dell’anatomia, della fisiologia e della connettività funzionale di specifiche aree cerebrali, ma consentono anche di localizzare determinate aree legate all’insorgenza e alla propagazione della crisi epilettica. Sono stati riportati studi clinici recenti che hanno investigato sull’uso di queste tecniche al fine di localizzare la zona epilettogena nei pazienti. Inoltre, gli studi si sono incentrati anche sullo sviluppo e sulla propagazione della crisi epilettica, fornendo delle indicazioni sulle possibili prospettive future relative alla tecnologia e all’elaborazione dei dati. L’analisi verrà condotta approfondendo le principali apparecchiature responsabili degli attuali sviluppi nelle ricerche sull’epilessia. Nello specifico, si effettuerà l’analisi della strumentazione partendo dai principi fisici alla base del suo funzionamento, per poi descriverne la struttura, le modalità di impiego per la specifica indagine e i futuri sviluppi.

Language lateralization correlates with verbal memory performance in children with focal epilepsy

PURPOSE: Assessment of language dominance with functional magnetic resonance imaging (fMRI) and neuropsychological evaluation is often used prior to epilepsy surgery. This study explores whether language lateralization and cognitive performance are systematically related in young patients with focal epilepsy. METHODS: Language fMRI and neuropsychological data (language, visuospatial functions, and memory) of 40 patients (7-18 years of age) with unilateral, refractory focal epilepsy in temporal and/or frontal areas of the left (n = 23) or right hemisphere (n = 17) were analyzed. fMRI data of 18 healthy controls (7-18 years) served as a normative sample. A laterality index was computed to determine the lateralization of activation in three regions of interest (frontal, parietal, and temporal). RESULTS: Atypical language lateralization was demonstrated in 12 (30%) of 40 patients. A correlation between language lateralization and verbal memory performance occurred in patients with left-sided epilepsy over all three regions of interest, with bilateral or right-sided language lateralization being correlated with better verbal memory performance (Word Pairs Recall: frontal r = -0.4, p = 0.016; parietal r = -0.4, p = 0.043; temporal r = -0.4, p = 0.041). Verbal memory performance made the largest contribution to language lateralization, whereas handedness and side of seizures did not contribute to the variance in language lateralization. DISCUSSION: This finding reflects the association between neocortical language and hippocampal memory regions in patients with left-sided epilepsy. Atypical language lateralization is advantageous for verbal memory performance, presumably a result of transfer of verbal memory function. In children with focal epilepsy, verbal memory performance provides a better idea of language lateralization than handedness and side of epilepsy and lesion.

Association of individual resting state EEG alpha frequency and cerebral blood flow

Cognitive task performance differs considerably between individuals. Besides cognitive capacities, attention might be a source of such differences. The individual's EEG alpha frequency (IAF) is a putative marker of the subject's state of arousal and attention, and was found to be associated with task performance and cognitive capacities. However, little is known about the metabolic substrate (i.e. the network) underlying IAF. Here we aimed to identify this network. Correlation of IAF with regional Cerebral Blood Flow (rCBF) in fifteen young healthy subjects revealed a network of brain areas that are associated with the modulation of attention and preparedness for external input, which are relevant for task execution. We hypothesize that subjects with higher IAF have pre-activated task-relevant networks and thus are both more efficient in the task-execution, and show a reduced fMRI-BOLD response to the stimulus, not because the absolute amount of activation is smaller, but because the additional activation by processing of external input is limited due to the higher baseline.