Twenty years have passed since the dysconnection hypothesis was first proposed (Friston and Frith, 1995; Weinberger, 1993). In that time, neuroscience has witnessed tremendous advances: we now live in a world of non-invasive neuroanatomy, computational neuroimaging and the Bayesian brain. The genomics era has come and gone. Connectomics and large-scale neuroinformatics initiatives are emerging everywhere. So where is the dysconnection hypothesis now? This article considers how the notion of schizophrenia as a dysconnection syndrome has developed – and how it has been enriched by recent advances in clinical neuroscience. In particular, we examine the dysconnection hypothesis in the context of (i) theoretical neurobiology and computational psychiatry; (ii) the empirical insights afforded by neuroimaging and associated connectomics – and (iii) how bottom-up (molecular biology and genetics) and top-down (systems biology) perspectives are converging on the mechanisms and nature of dysconnections in schizophrenia.

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PurposeShape and exact location of motor cortical areas varies among individuals. The exact knowledge of these locations is crucial for planning of neurosurgical procedures. In this study, we have used robot-assisted image-guided transcranial magnetic stimulation (Ri-TMS) to elicit MEP response recorded for individual muscles and reconstruct functional motor maps of the primary motor cortex.MethodsOne healthy volunteer and five patients with intracranial tumors neighboring the precentral gyrus were selected for this pilot study. Conventional MRI and fMRI were obtained. Transcranial magnetic stimulation was performed using a MagPro X100 stimulator and a standard figure-of-eight coil positioned by an Adept Viper s850 robot. The fMRI activation/Ri-TMS response pattern were compared. In two cases, Ri-TMS was additionally compared to intraoperative direct electrical cortical stimulation.ResultsMaximal MEP response of the m. abductor digiti minimi was located in an area corresponding to the “hand knob” of the precentral gyrus for both hemispheres. Repeated Ri-TMS measurements showed a high reproducibility. Simultaneous registration of the MEP response for m. brachioradialis, m. abductor pollicis brevis, and m. abductor digiti minimi demonstrated individual peak areas of maximal MEP response for the individual muscle groups. Ri-TMS mapping was compared to the corresponding fMRI studies. The areas of maximal MEP response localized within the “finger tapping” activated areas by fMRI in all six individuals.ConclusionsRi-TMS is suitable for high resolution non-invasive preoperative somatotopic mapping of the motor cortex. Ri-TMS may help in the planning of neurosurgical procedures and may be directly used in navigation systems.