Publications

Several procedures have been developed to enhance the rehabilitation of stroke patients. However, most techniques struggle to promote sustained recovery in the months following the treatment. Therefore, it is essential to understand the mechanisms that can be harnessed during treatment to potentiate retention of benefits and sustained recovery. While stroke patients often suffer from thalamocortical dysrhythmia (TCD), a perturbation in alpha (8-13 Hz) rhythms caused by decreased excitation in the cortico-thalamic projections, the functional relevance of TCD in stroke patients is not yet clear. We propose that TCD can be counteracted by combining focal stimulation of the motor cortex with virtual-reality (VR) based rehabilitation, which engages distributed networks associated with goal-oriented behavior. Critically, we investigate whether this can be the key to promoting sustained recovery in stroke patients. We compare thalamocortical rhythms and behavioral recovery in patients receiving Sham and bilateral tDCS stimulation of the motor cortex during therapy with the Rehabilitation Gaming System (RGS). Our results reveal that patients in the tDCS group show a sustained recovery in all clinical scales up to three months post-treatment, as opposed to the Sham group. Furthermore, we demonstrate that the slowing down of alpha rhythms can be counteracted by transcranial direct-current stimulation (tDCS), with a particular role for enhancing the excitability of parietal areas. That said, we found no correlation between changes in alpha rhythms and motor recovery. On one hand, our findings suggest that sustained recovery can be potentiated by tDCS-enhanced VR-based rehabilitation. On the other hand, enhancing the excitability of parietal areas while recruiting brain networks associated with goal-oriented behavior can successfully counteract TCD, even though this is likely not the main driver of sustained motor recovery.

JTD Keywords: Activation, Alpha rhythms, Deep brain-stimulation, Direct-current stimulation, Excitatory-inhibitory balance, Guidelines, Human thalamus, Involvement, Motor recovery, Quality-of-life, Rehabilitation, Sensitivity, Stroke, Transcranial direct-current stimulation

Experimental and clinical studies of consciousness identify brain states (i.e. quasi-stable functional cerebral organization) in a non-systematic manner and largely independent of the research into brain state modulation. In this narrative review, we synthesize advances in the identification of brain states associated with consciousness in animal models and physiological (sleep), pharmacological (anaesthesia) and pathological (disorders of consciousness) states of altered consciousness in humans. We show that in reduced consciousness the frequencies in which the brain operates are slowed down and that the pattern of functional communication is sparser, less efficient, and less complex. The results also highlight damaged resting-state networks, in particular the default mode network, decreased connectivity in long-range connections and especially in the thalamocortical loops. Next, we show that therapeutic approaches to treat disorders of consciousness, through pharmacology (e.g. amantadine, zolpidem), and (non-) invasive brain stimulation (e.g. transcranial direct current stimulation, deep brain stimulation) have shown partial effectiveness in promoting consciousness recovery. Although some features of conscious brain states may improve in response to neuromodulation, targeting often remains non-specific and does not always lead to (behavioural) improvements. The fields of brain state identification and neuromodulation of brain states in relation to consciousness are showing fascinating developments that, when integrated, might propel the development of new and better-targeted techniques for disorders of consciousness. We here propose a therapeutic framework for the identification and modulation of brain states to facilitate the interaction between the two fields. We propose that brain states should be identified in a predictive setting, followed by theoretical and empirical testing (i.e. in animal models, under anaesthesia and in patients with a disorder of consciousness) of neuromodulation techniques to promote consciousness in line with such predictions. This framework further helps to identify where challenges and opportunities lay for the maturation of brain state research in the context of states of consciousness. It will become apparent that one angle of opportunity is provided through the addition of computational modelling. Finally, it aids in recognizing possibilities and obstacles for the clinical translation of these diagnostic techniques and neuromodulation treatment options across both the multimodal and multi-species approaches outlined throughout the review.

JTD Keywords: (disorders of) consciousness, Anaesthesia, Animal model, Animal models, Area induces reanimation, Brain states, Direct-current stimulation, Disorder, Electrical-stimulation, Functional connectivity, General-anesthesia, Neuromodulation, Propofol-induced loss, Thalamic-stimulation, Transcranial magnetic stimulation, Vegetative state