**7. Pathological changes in the functional connectome**

To know the role of cortical afferents in the striatal microcircuit, we used decorticated striatal slices. The decorticated striatal microcircuit preserves some active network states conforming temporal sequences, albeit alternation between ensembles is greatly reduced. In fact, network analysis revealed a loss of active hub neurons [9]. This result suggested that cortical afferents maintain privileged connections with striatal hub neurons, probably interneurons, to organize striatal activity.

Similarly, in the rodent model of Parkinson's disease, there is a significant loss of hub active neurons. Not strangely, the Parkinsonian striatal microcircuit shows less transitions between network states, confirming that one larger neuronal ensemble becomes dominant [8, 38], recruiting the majority of active neurons [9]. These results indicate that the majority of hub neurons are functionally eliminated during dopamine deprivation and a remaining set of hub neurons help to maintain the dominant state. This is supported by studies that suggest a breakdown of corticostriatal connectivity during Parkinson's disease [60, 61]. Other studies show potentiation of synaptic currents of some classes of interneurons [62, 63]. It is also known that drugs as L-DOPA or nicotine could return the microcircuit to control conditions [38, 39], implying that hub neurons are not physically eliminated during dopamine deprivation. The role of the interneurons has been recently addressed [9], since previous studies did not consider them [64].

In the L-DOPA-induced dyskinesia model, the microcircuit keeps showing a significant increase in activity with respect to the controls. In fact, more functional connections and even more hub neurons, and more transitions between network states correlate with the increase of prokinetic gamma rhythms described in dyskinetic subjects [65]. The "return" of hub neurons confirmed that they were not physically but only functionally removed during the Parkinsonian state. Their reappearance during dyskinesia indicates that they are necessary in the striatal microcircuit to produce movements. Nevertheless, the dyskinetic striatal microcircuit exhibited a loss of hierarchical modules [9]. This finding could be seen as a correlate of the excessive disordered movements present in dyskinetic subjects.
