Statistical methods for biomedical signal analysis and processing

Statistical modelling and statistical learning theory are two powerful analytical frameworks for analyzing signals and developing efficient processing and classification algorithms. In this thesis, these frameworks are applied for modelling and processing biomedical signals in two different contexts: ultrasound medical imaging systems and primate neural activity analysis and modelling. In the context of ultrasound medical imaging, two main applications are explored: deconvolution of signals measured from a ultrasonic transducer and automatic image segmentation and classification of prostate ultrasound scans. In the former application a stochastic model of the radio frequency signal measured from a ultrasonic transducer is derived. This model is then employed for developing in a statistical framework a regularized deconvolution procedure, for enhancing signal resolution. In the latter application, different statistical models are used to characterize images of prostate tissues, extracting different features. These features are then uses to segment the images in region of interests by means of an automatic procedure based on a statistical model of the extracted features. Finally, machine learning techniques are used for automatic classification of the different region of interests. In the context of neural activity signals, an example of bio-inspired dynamical network was developed to help in studies of motor-related processes in the brain of primate monkeys. The presented model aims to mimic the abstract functionality of a cell population in 7a parietal region of primate monkeys, during the execution of learned behavioural tasks.

Controllo dell'atto di prensione: coinvolgimento dell'area V6A nell'orientamento del polso

Prehension in an act of coordinated reaching and grasping. The reaching component is concerned with bringing the hand to object to be grasped (transport phase); the grasping component refers to the shaping of the hand according to the object features (grasping phase) (Jeannerod, 1981). Reaching and grasping involve different muscles, proximal and distal muscles respectively, and are controlled by different parietofrontal circuit (Jeannerod et al., 1995): a medial circuit, involving area of superior parietal lobule and dorsal premotor area 6 (PMd) (dorsomedial visual stream), is mainly concerned with reaching; a lateral circuit, involving the inferior parietal lobule and ventral premotor area 6 (PMv) (dorsolateral visual stream), with grasping. Area V6A is located in the caudalmost part of the superior parietal lobule, so it belongs to the dorsomedial visual stream; it contains neurons sensitive to visual stimuli (Galletti et al. 1993, 1996, 1999) as well as cells sensitive to the direction of gaze (Galletti et al. 1995) and cells showing saccade-related activity (Nakamura et al. 1999; Kutz et al. 2003). Area V6A contains also arm-reaching neurons likely involved in the control of the direction of the arm during movements towards objects in the peripersonal space (Galletti et al. 1997; Fattori et al. 2001). The present results confirm this finding and demonstrate that during the reach-to-grasp the V6A neurons are also modulated by the orientation of the wrist. Experiments were approved by the Bioethical Committee of the University of Bologna and were performed in accordance with National laws on care and use of laboratory animals and with the European Communities Council Directive of 24th November 1986 (86/609/EEC), recently revised by the Council of Europe guidelines (Appendix A of Convention ETS 123). Experiments were performed in two awake Macaca fascicularis. Each monkey was trained to sit in a primate chair with the head restrained to perform reaching and grasping arm movements in complete darkness while gazing a small fixation point. The object to be grasped was a handle that could have different orientation. We recorded neural activity from 163 neurons of the anterior parietal sulcus; 116/163 (71%) neurons were modulated by the reach-to-grasp task during the execution of the forward movements toward the target (epoch MOV), 111/163 (68%) during the pulling of the handle (epoch HOLD) and 102/163 during the execution of backward movements (epoch M2) (t_test, p ≤ 0.05). About the 45% of the tested cells turned out to be sensitive to the orientation of the handle (one way ANOVA, p ≤ 0.05). To study how the distal components of the movement, such as the hand preshaping during the reaching of the handle, could influence the neuronal discharge, we compared the neuronal activity during the reaching movements towards the same spatial location in reach-to-point and reach-to-grasp tasks. Both tasks required proximal arm movements; only the reach-to-grasp task required distal movements to orient the wrist and to shape the hand to grasp the handle. The 56% of V6A cells showed significant differences in the neural discharge (one way ANOVA, p ≤ 0.05) between the reach-to-point and the reach-to-grasp tasks during MOV, 54% during HOLD and 52% during M2. These data show that reaching and grasping are processed by the same population of neurons, providing evidence that the coordination of reaching and grasping takes place much earlier than previously thought, i.e., in the parieto-occipital cortex. The data here reported are in agreement with results of lesions to the medial posterior parietal cortex in both monkeys and humans, and with recent imaging data in humans, all of them indicating a functional coupling in the control of reaching and grasping by the medial parietofrontal circuit.

Coding of reaching in 3-D space

Many psychophysical studies suggest that target depth and direction during reaches are processed independently, but the neurophysiological support to this view is so far limited. Here, we investigated the representation of reach depth and direction by single neurons in an area of the medial posterior parietal cortex (V6A). Single-unit activity was recorded from V6A in two Macaca fascicularis monkeys performing a fixation-to-reach task to targets at different depths and directions. We found that in a substantial percentage of V6A neurons depth and direction signals jointly influenced fixation, planning and arm movement-related activity in 3D space. While target depth and direction were equally encoded during fixation, depth tuning became stronger during arm movement planning, execution and target holding. The spatial tuning of fixation activity was often maintained across epochs, and this occurred more frequently in depth. These findings support for the first time the existence of a common neural substrate for the encoding of target depth and direction during reaching movements in the posterior parietal cortex. Present results also highlight the presence in V6A of several types of cells that process independently or jointly eye position and arm movement planning and execution signals in order to control reaches in 3D space. It is possible that depth and direction influence also the metrics of the reach action and that this effect on the reach kinematic variables can account for the spatial tuning we found in V6A neural activity. For this reason, we recorded and analyzed behavioral data when one monkey performed reaching movements in 3-D space. We evaluated how the target spatial position, in particular target depth and target direction, affected the kinematic parameters and trajectories describing the motor action properties.

The role of medial parieto occipital cortex in visuospatial attention and reach planning: electrophysiological studies in human and non-human primates

We usually perform actions in a dynamic environment and changes in the location of a target for an upcoming action require both covert shifts of attention and motor planning update. In this study we tested whether, similarly to oculomotor areas that provide signals for overt and covert attention shifts, covert attention shifts modulate activity in cortical area V6A, which provides a bridge between visual signals and arm-motor control. We performed single cell recordings in monkeys trained to fixate straight-ahead while shifting attention outward to a peripheral cue and inward again to the fixation point. We found that neurons in V6A are influenced by spatial attention demonstrating that visual, motor, and attentional responses can occur in combination in single neurons of V6A. This modulation in an area primarily involved in visuo-motor transformation for reaching suggests that also reach-related regions could directly contribute in the shifts of spatial attention necessary to plan and control goal-directed arm movements. Moreover, to test whether V6A is causally involved in these processes, we have performed a human study using on-line repetitive transcranial magnetic stimulation over the putative human V6A (pV6A) during an attention and a reaching task requiring covert shifts of attention and reaching movements towards cued targets in space. We demonstrate that the pV6A is causally involved in attention reorienting to target detection and that this process interferes with the execution of reaching movements towards unattended targets. The current findings suggest the direct involvement of the action-related dorso-medial visual stream in attentional processes, and a more specific role of V6A in attention reorienting. Therefore, we propose that attention signals are used by the V6A to rapidly update the current motor plan or the ongoing action when a behaviorally relevant object unexpectedly appears at an unattended location.