Marco Bove

Dissociated cortical networks show spontaneously correlated activity patterns during in vitro development.

In vitro cultured neuronal networks coupled to microelectrode arrays (MEAs) constitute a valuable experimental model for studying changes in the neuronal dynamics at different stages of development. After a few days in culture, neurons start to connect each other with functionally active synapses, forming a random network and displaying spontaneous electrophysiological activity. The patterns of collective rhythmic activity change in time spontaneously during in vitro development. Such activity-dependent modifications play a key role in the maturation of the network and reflect changes in the synaptic efficacy, fact widely recognized as a cellular basis of learning, memory and developmental plasticity. Getting advantage from the possibilities offered by the MEAs, the aim of our study is to analyze and characterize the natural changes in dynamics of the electrophysiological activity at different ages of the culture, identifying peculiar steps of the spontaneous evolution of the network. The main finding is that between the second and the third week of culture, the network completely changes its electrophysiological patterns, both in terms of spiking and bursting activity and in terms of cross-correlation between pairs of active channels. Then the maturation process can be characterized by two main phases: modulation and shaping in the synaptic functional connectivity of the network (within the first and second week) and general moderate correlated activity, spread over the entire network, with connections properly formed and stabilized (within the fourth and fifth week).

Effect of cognitive and motor tasks on postural stability in Parkinson's disease: a posturographic study.

To analyse the effect of concomitant cognitive or motor task performance on balance control in Parkinsons disease (PD), we performed a posturographic study in 24 PD patients and in 20 sex‐ and age‐matched control subjects. Postural sway was measured with eyes open (EO) and eyes closed (EC) during quiet stance and during performance of calculation or motor sequence of thumb opposition to the other fingers. No difference of centre of foot pressure (COP) parameters was observed during quiet standing (either EO or EC) between patients and controls, but visual deprivation induced in both groups a worsening of postural stability. COP area was significantly increased in PD patients during dual task performance, whereas no difference of COP path and x–y axes was observed. The effects induced by the performance of cognitive or motor task were significantly more evident in PD patients with clinical evidence of postural instability (presence of prior falls in the history). This study demonstrates that dual task interference on postural control can be observed in PD patients during performance of cognitive as well as motor tasks. The balance deterioration during dual task performance was significantly enhanced in patients with history of prior falls. These findings have some implications for the strategies to be used in reducing the risk of fall in PD.

Callosal Contributions to Simultaneous Bimanual Finger Movements

Corpus callosum (CC) is involved in the performance of bimanual motor tasks. We asked whether its functional role could be investigated by combining a motor behavioral study on bimanual movements in multiple sclerosis (MS) patients with a quantitative magnetic resonance diffusion tensor imaging (DTI) analysis of CC, which is shown to be damaged in this disease. MS patients and normal subjects were asked to perform sequences of bimanual finger opposition movements at different metronome rates; then we explored the structural integrity of CC by means of DTI. Significant differences in motor performance, mainly referred to timing accuracy, were observed between MS patients and control subjects. Bimanual motor coordination was impaired in MS patients as shown by the larger values of the interhand interval observed at all the tested metronome rates with respect to controls. Furthermore, DTI revealed a significant reduction of fractional anisotropy (FA), indicative of microstructural tissue damage, in the CC of MS patients. By correlating the mean FA values with the different motor behavior parameters, we found that the degree of damage in the anterior callosal portions mainly influences the bimanual coordination and, in particular, the movement phase preceding the finger touch. Finally, the described approach, which correlates quantitative measures of tissue damage obtained by advanced magnetic resonance imaging tools with appropriate behavioral measurements, may help the exploration of different aspects of motor performance impairment attributable to the disease.

Action observation improves freezing of gait in patients with Parkinson's disease

Background. Freezing of gait (FOG) is a disabling impairment for people with Parkinson’s disease (PD) and may not respond to medications. The effectiveness of physical therapy for FOG is debatable. Action observation strategies to overcome FOG may enhance physical training. Objective. To assess whether action observation, combined with practicing the observed actions, may reduce FOG episodes. Methods. Twenty patients with PD entered a single-blind trial and were randomly assigned to the experimental (Action) or control (Landscape) groups. Those in the Action group watched video clips showing specific movements and strategies to circumvent FOG episodes, whereas those in the Landscape group watched video clips of static pictures showing different landscapes. All patients underwent identical physical therapy training, 3 sessions a week for 4 weeks. Results. The FOG Questionnaire score and the number of FOG episodes were significantly reduced in both groups after the training period. At follow-up examination (4 weeks after the end of the intervention), a significant reduction in the number of FOG episodes was observed only in the Action group. Motor performance (walking and balance) and quality-of-life assessments were significantly improved in both groups at the end of training and at follow-up. Conclusions. Our results suggest that action observation has a positive additional effect on recovery of walking ability in PD patients with FOG. Further studies on the combination of observation and imitation to supplement a physical training program may result in an innovative rehabilitative approach for FOG.

Cultured neurons coupled to microelectrode arrays: circuit models, simulations and experimental data

The purpose of this paper is to characterize the neuron-microelectrode junction, based on the equivalent electric-circuit approach. As a result, recording of action potentials can be simulated with a general-purpose circuit simulation program such as HSPICE. The response of the microelectrode was analyzed as a function of parameters such as sealing resistance and adhesion conditions. The models of the neuron and microelectrode implemented in HSPICE were first described. These models were used to simulate the behavior of the junction between a patch of neuronal membrane (described by the compartmental model) and a microelectrode.

Experimental analysis of neuronal dynamics in cultured cortical networks and transitions between different patterns of activity

Abstract. Experimental investigation of the dynamics of biological networks is a fundamental step towards understanding how the nervous system works. Spontaneous activity in cultured networks of cortical neurons has been investigated by using a multisite recording technique with planar electrode arrays. In these networks, the spatiotemporal firing patterns were studied in the presence of different extracellular solutions. Transitions from asynchronous firing dynamics to synchronous firing dynamics were observed when the extracellular Ca2+ concentration was increased from 0.1 mM to 1 mM. Addition of extracellular Mg2+ reduced the spontaneous activity at any Ca2+ concentration, and an increase in the extracellular K+ concentration enhanced the frequency of periodical synchronous bursts. N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor antagonists inhibited synchronous activity. A spatiotemporal analysis of the data has been performed, and the properties of the network such as the synchronization and the periodicity have been quantified in order to clarify how variations of intrinsic parameters of the network can induce structural transitions in the neural dynamics. This experimental study is a possible approach to investigate the computational properties of a neuronal network.

The serial reaction time task revisited: a study on motor sequence learning with an arm-reaching task

With a series of novel arm-reaching tasks, we have shown that visuomotor sequence learning encompasses the acquisition of the order of sequence elements, and the ability to combine them in a single, skilled behavior. The first component, which is mostly declarative, is reflected by changes in movement onset time (OT); the second, which occurs without subject’s awareness, is measured by changes in kinematic variables, including movement time (MT). Key-press-based serial reaction time tasks (SRTT) have been used to investigate sequence learning and results interpreted as indicative of the implicit acquisition of the sequence order. One limitation to SRT studies, however, is that only one measure is used, the response time, the sum of OT and MT: this makes interpretation of which component is learnt difficult and disambiguation of implicit and explicit processes problematic. Here, we used an arm-reaching version of SRTT to propose a novel interpretation of such results. The pattern of response time changes we obtained was similar to the key-press-based tasks. However, there were significant differences between OT and MT, suggesting that both partial learning of the sequence order and skill improvement took place. Further analyses indicated that the learning of the sequence order might not occur without subjects’ awareness.

Short-Term Limb Immobilization Affects Motor Performance

C. Ghez, J. Gordon, and M. R Ghilardi (1995; J. Gordon, M. R Ghilardi, & C. Ghez, 1995; R. L. Sainburg, M. R Ghilardi, H. Poizner, & C. Ghez, 1995) have found that proprio-ceptive deafferentation impairs feedforward and feedback mechanisms that control reaching movements. In the present study, the authors found immobilization-induced changes in limb kinematics, including joint motion, in 32 healthy participants who performed out-and-back movements before and after 0, 6, or 12 hr of immobilization of the left arm. Control participants did not undergo the arm immobilization procedure. Immobilization for 12 hr, but not 6 hr, caused trajectories with increased hand-path areas and altered interjoint coordination. The abnormalities were smaller in amplitude but similar in quality to those reported in deafferented patients (R. L. Sainburg et al.). In addition, movement onset point significantly drifted after immobilization. Thus, short-term limb disuse can affect interjoint coordination by acting on feedforward mechanisms. These behavioral alterations are potentially related to cortical plastic changes.

An array of Pt-tip microelectrodes for extracellular monitoring of activity of brain slices

A microelectrode array (MEA) consisting of 34 silicon nitride passivated Pt-tip microelectrodes embedded on a perforated silicon substrate (porosity 35%) has been realized. The electrodes are 47 microns high, of which only the top 15 microns are exposed Pt-tips having a curvature of 0.5 micron. The MEA is intended for extracellular recordings of brain slices in vitro. Here we report the fabrication, characterization and initial electrophysiological evaluation of the first generation of Pt-tip MEAs.

Use-dependent hemispheric balance.

In the human brain, homologous regions of the primary motor cortices (M1s) are connected through transcallosal fibers. Interhemispheric communication between the two M1s plays a major role in the control of unimanual hand movements, and the strength of this connection seems to be dependent on arm activity. For instance, a lesion in the M1 can induce an increase in the excitability of the intact M1 and an abnormal high inhibitory influence onto the damaged M1. This can be attributable to either the disuse of the affected limb or the overuse of the unaffected one. Here, to directly investigate cortical modifications induced by an abnormal asymmetric use of the two limbs, we studied both the excitability of the two M1s and transcallosal interaction between them in healthy subjects whose right hand was immobilized for 10 h. The left “not-immobilized” arm was completely free to move in one group of participants (G1) and limited in the other one (G2). We found that the non-use reduced the excitability of the left M1 and decreased the inhibitory influence onto the right hemisphere in the two groups. However, an increase in the excitability of right M1 and a deeper inhibitory interaction onto the left hemisphere were evident only in G1. Thus, modifications in the right M1 were not directly produced by the non-use but would depend on the overuse of the “not-immobilized” arm. Our findings suggest that the balance between the two M1s is strongly use dependent.