**5. Cortical connectivity and coma**

During coma states as during the anesthesia, there is a decrease in connectivity ("communication") between different cortical regions, or between cortical and subcortical regions, caused by a reduction of cerebral activity. The basis of cortical connectivity is made of structural links, such as synapses and neural fibers.

In clinical practice, the evaluation of connectivity is performed by analyzing the coherence/ correlation between biological signals (EEG, ECoG and local-field potentials) from different regions of the brain.

*Functional connectivity* is based on biological signals analysis, which can be described as time series (such as the EEG) and can quantify cortical connectivity using statistical analysis (correlation) of the EEG signals from different cortical areas. The better the EEG signals are correlated (estimated by the correlation coefficient, XAppEn, mscohere), the more they are alike; therefore, there is a good connectivity between the cortical areas. Importantly, good statistical correlation of biological signals does not necessarily involve causality, and does not point out the direction the information moves [80]. Unlike structural connectivity, functional connectivity is time-dependent [81].

*Effective connectivity* may be regarded as a unit of structural and functional connectivity. It is the latest instrument trying to establish causal relations between neural network components [81]. Effective connectivity is calculated using complex mathematical algorithms (such as Granger causality or transfer entropy), applied to time series.

The state of consciousness, according to Buzsaki (2007), is the consequence of the functional transformation of information contained by a neural network. Both posterior parietal and prefrontal association areas and frontoparietal network information integration were considered involved in the generation and maintenance of the state of consciousness [82, 83]. During sleep, which is a reversible modification of consciousness as well, there is a modification of cortical connectivity; therefore, during NREM sleep, it lowers and during REM sleep, it increases [84].

Cortical connectivity changes during anesthesia were first observed in lab animals, and then in humans. Thus, in 2005, the cortical connectivity changes, especially in the prefrontal cortex, during sevoflurane anesthesia of different concentrations, were described. Bouveroux et al. described the effects of propofol on cortical connectivity: during propofol anesthesia, corticocortical and thalamocortical connectivity decreases in frontal-parietal networks, while it is maintained in the visual and auditory cortex [85]. Mhuircheartaigh et al. regard the lack of response to auditory and pain stimuli during propofol anesthesia as a consequence of putamencortex connectivity decreases, while thalamocortical connectivity remains unchanged [86]. Ferrarelli et al. notice as well the frontal intracortical connectivity decreases, during transcranial magnetic stimulation, under midazolam sedation [87]. Cortical connectivity is disrupted in several pathological states, such as brain trauma, vegetative state and memory or attention loss.

During mild brain trauma, there have been described frontal and occipital cortical connectivity changes, a decrease of intercortical connectivity over longer distances and an increase of cortical connectivity over shorter distances [88]. The vegetative state is defined as the abolishing of consciousness, while excitatory external factors are present. While in vegetative state, there is a decrease of cortical connectivity in several areas: prefrontal and premotor cortex, temporal-parietal association areas and posterior cingulate cortex. Furthermore, there is an altered connectivity between prefrontal and premotor cortical areas and posterior cingulate cortex [89]. Subcortical cerebrovascular accidents alter cortical connectivity between the two hemispheres: between supplementary motor areas and between ipsilateral supplementary motor area and lateral premotor area. These neural connectivity modifications, both under physiological and under pathological conditions, make cortical connectivity, if not the most sensitive, among the most sensitive parameters of nervous function.
