Keywords:Vegetative state Unresponsive wakefulness syndrome Minimally conscious state Brain injury Transcranial magnetic stimulation Motor evoked potentials Somatosensory evoked potentials Short latency afferent inhibition a b s t r a c t Background: Transcranial magnetic stimulation (TMS) has been frequently used to explore changes in the human motor cortex in different conditions, while the extent of motor cortex reorganization in patients in vegetative state (VS) (now known as unresponsive wakefulness syndrome, UWS) and minimally conscious (MCS) states due to severe brain damage remains largely unknown. Objective/hypothesis: It was hypothesized that cortical motor excitability would be decreased and would correlate to the level of consciousness in patients with disorders of consciousness. Methods: Corticospinal excitability was assessed in 47 patients (24 VS/UWS and 23 MCS) and 14 healthy controls. The test parameters included maximal peak-to-peak M-wave (M max ), F-wave persistence, peripheral and central motor conduction times, sensory (SEP) and motor evoked (MEP) potential latencies and amplitudes, resting motor threshold (RMT), stimulus/response curves, and short latency afferent inhibition (SAI). TMS measurements were correlated to the level of consciousness (assessed using the Coma Recovery Scale-Revised). Results: On average, the patient group had lower M max , lower MEP and SEP amplitudes, higher RMTs, narrower stimulus/response curves, and reduced SAI compared to the healthy controls (P < 0.05). The SAI alterations were correlated to the level of consciousness (P < 0.05). Conclusions:The findings demonstrated the impairment of the cortical inhibitory circuits in patients with disorders of consciousness. Moreover, the significant relationship was found between cortical inhibition and clinical consciousness dysfunction.Ó 2013 Elsevier Inc. All rights reserved. IntroductionFollowing severe brain damage, disorders of consciousness (DOC), such as vegetative state (VS) (now known as unresponsive wakefulness syndrome, UWS) [1] or minimally conscious state (MCS) have been linked to poor long term prognosis [2]. The recovery of consciousness could be related to the number of surviving neurons and the functional integrity of long-range cortico-cortical and cortico-thalamo-cortical connections [3]. Transcranial magnetic stimulation (TMS) is an objective method to assess the motor cortex excitability and the integrity of motor pathways [4]. Several studies indicate that cortical injuries, independent of their etiology, can lead to a reduced strength of inhibitory neurotransmission [5e8]. Paired TMS has been used for over 20 years to investigate recovery of motor function in stroke patients [9]. Cortical excitability is also shown to correlate with the severity of brain damage in patients with diffuse traumatic brain injury (TBI) [10e14] and to be related to the clinical recovery in mild to moderate TBI [15]. By coupling peripheral nerve stimulation with TMS, it is possible to modify the excitability of the mot...

Training of specific muscles causes plastic changes in corticomotor pathways which may underlie the effect of various clinical rehabilitation procedures. The paired pulse transcranial magnetic stimulation (ppTMS) technique can be used to assess short interval intra-cortical inhibitory (SICI) and intra-cortical facilitatory (ICF) networks. This study examined changes in SICI and ICF in tongue motor cortex after tongue training in 11 healthy volunteers using ppTMS. Paired pulse TMS was applied to the 'hot-spot' for the tongue motor cortex and motor-evoked potentials (MEPs) were recorded from tongue muscles. In tongue motor cortex, bilateral SICI (P < 0.019) and ICF (P < 0.001) was detected before and after training. There were no significant effects of training on single MEPs or SICI/ICF (P > 0.063). The success rate improved during training (P < 0.001) and changes in success were correlated to changes in single MEP amplitude (P < 0.006) but not to SICI/ICF (P > 0.113). This first study of SICI/ICF after tongue training showed no training-related changes in intra-cortical inhibitory or facilitatory networks. However, there was an association between task performance and changes in corticomotor excitability. Further studies are required to determine the clinical utility of muscle specific training for oral rehabilitation purposes.

Transcranial magnetic stimulation (TMS) is a noninvasive means of investigating the function, plasticity, and excitability of the human brain. TMS induces a brief intracranial electrical current, which produces action potentials in excitable cells. Stimulation applied over the motor cortex can be used to measure overall excitability of the corticospinal system, somatotopic representation of muscles, and subsequent plastic changes following injury. The facilitation and inhibition characteristics of the cerebral cortex can also be compared using the modulatory effect of a conditioning stimulus preceding a test stimulus. So called paired-pulse protocols have been used in humans and animals to assess GABA (g-amino-butyric acid)-ergic function and may have a future role directing therapeutic interventions. Indeed, repetitive magnetic stimulation, where intracranial currents are induced by repetitive stimulation higher than 1 Hz, has been shown to modulate brain responses to sensory and cognitive stimulation. Here, we summarize information gathered using TMS with patients in coma, vegetative state, and minimally conscious state. Although in the early stages of investigation, there is preliminary evidence that TMS represents a promising tool by which to elucidate the pathophysiological sequelae of impaired consciousness and potentially direct future therapeutic interventions. We will discuss the methodology of work conducted to date, as well as debate the general limitations and pitfalls of TMS studies in patients with altered states of consciousness.

Keywords:Brain injury Motor evoked potential Transcranial magnetic stimulation Short latency afferent inhibition a b s t r a c t Background: Transcranial magnetic stimulation (TMS) have been frequently used to explore changes in motor cortex excitability in stroke and traumatic brain injury, while the extent of motor cortex reorganization in patients with diffuse non-traumatic brain injury remains largely unknown. Objective/hypothesis: It was hypothesized that the motor cortex excitability would be decreased and would correlate to the severity of brain injury and level of functioning in patients with anoxic, traumatic, and non-traumatic diffuse brain injury. Methods: TMS was applied to primary motor cortices of 19 patients with brain injury (5 traumatic and 14 non-traumatic causes; on average four months after insult), and 9 healthy controls. The test parameters included resting motor threshold (RMT), short intracortical inhibition (SICI), intracortical facilitation (ICF), and short latency afferent inhibition (SAI). Excitability parameters were correlated to the severity of brain injury measured with Glasgow Coma Scale and the level of functioning assessed using the Ranchos Los Amigos Levels of Cognitive Functioning Assessment Scale and Functional Independence Measure. Results: The patient group revealed a significantly decreased SICI and SAI compared to healthy controls with the amount of SICI correlated significantly to the severity of brain injury. Other electrophysiological parameters did not differ between the groups and did not exhibit any significant relationship with clinical functional scores.Conclusions: The present study demonstrated the impairment of the cortical inhibitory circuits in patients with brain injury of traumatic and non-traumatic aetiology. Moreover, the significant correlation was found between the amount of SICI and the severity of brain injury.

The study showed that robotic gait training induced measurable changes in the EEG power spectrum in healthy individuals, while no changes were observed in patients with severe TBI. The absence of the EEG changes following training might be an indicator of the severity of brain dysfunction.