Neuroscience and Biobehavioral Reviews 37 (2013) 2721–2736 Contents lists available at ScienceDirect Neuroscience and Biobehavioral Reviews jou rn al h om epage: www.elsevier.com/locate/neubiorev Review Emerging from an unresponsive wakefulness syndrome: Brain plasticity has to cross a threshold level Sergio Bagnato a,* , Cristina Boccagni a , Antonino Sant’Angelo a , Alexander A. Fingelkurts b , Andrew A. Fingelkurts b , Giuseppe Galardi a a Unit of Neurophysiology and Unit for Severe Acquired Brain Injury, Rehabilitation Department, Fondazione Istituto San Raffaele G. Giglio, Cefalù, PA, Italy b BM-Science – Brain and Mind Technologies Research Centre, Espoo, Finland a r t i c l e i n f o Article history: Received 20 June 2013 Received in revised form 29 August 2013 Accepted 12 September 2013 Keywords: Vegetative state Minimally conscious state Consciousness Awareness Rehabilitation Recovery Cortex Thalamus Thalamocortical projections Brain hypoxia Traumatic brain injuries (TBI) EEG a b s t r a c t Unresponsive wakefulness syndrome (UWS, previously known as vegetative state) occurs after patients survive a severe brain injury. Patients suffering from UWS have lost awareness of themselves and of the external environment and do not retain any trace of their subjective experience. Current data demonstrate that neuronal functions subtending consciousness are not completely reset in UWS; however, they are reduced below the threshold required to experience consciousness. The critical factor that determines whether patients will recover consciousness is the distance of their neuronal functions from this threshold level. Recovery of consciousness occurs through functional and/or structural changes in the brain, i.e., through neuronal plasticity. Although some of these changes may occur spontaneously, a growing body of evidence indicates that rehabilitative interventions can improve functional outcome by promoting adaptive functional and structural plasticity in the brain, especially if a comprehensive neurophysiological theory of consciousness is followed. In this review we will focus on the pathophysiological mechanisms involved in UWS and on the plastic changes operating on the recovery of consciousness. © 2013 Elsevier Ltd. All rights reserved. Contents 1. Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2722 2. Brain areas or brain functions to explain consciousness impairment in UWS? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2722 2.1. Evidence from neuropathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2723 2.2. Evidence from neuroimaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2724 2.3. Evidence from neurophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2724 3. Where and how do plastic changes operate in order to recover consciousness? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2726 3.1. Plasticity in cortical areas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2727 3.2. Plasticity in thalamocortical and corticothalamic projections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2728 4. Current difficulties and strategies in the rehabilitation of patients with UWS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2729 5. Developing a rehabilitation specific for UWS and based on a neurophysiological theory of consciousness and on neuroplasticity tenets . . . . 2730 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2732 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2732 * Corresponding author at: Rehabilitation Department, Fondazione Istituto “San Raffaele – G. Giglio”, Viale G. Giardina, 90015 Cefalù, PA, Italy. Tel.: +39 921920357; fax: +39 921920253. E-mail address: sergiobagnato@gmail.com (S. Bagnato). 0149-7634/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.neubiorev.2013.09.007