Abstract
Objectives: A combined approach of behavioral characteristics and network properties was applied to explore the effect of repetitive transcranial magnetic stimulation (rTMS) on disorders of consciousness (DOC) and to observe changes in brain network connections before and after the stimulation.Methods: A total of 7 DOC patients and 11 healthy controls were enrolled. The study was designed as a randomized, sham-controlled study. All DOC patients were given 20 Hz rTMS real and sham stimuli to the left M1 region, with each stimulus lasting for 5 consecutive working days and the interval between two stimuli being 1 week. Coma Recovery Scale-Revised (CRS-R) and resting state functional MRI data before and after stimuli were collected. The functional connection (FC) of the default mode network and the frontoparietal network were chosen as the central target to compare differences in network connections between the DOC group and the normal control group. For DOC patients, changes in behavior and brain function before and after real and sham stimuli were also assessed as a group and individually.Results: (1). The overall analyses showed no significant changes of CRS-R scores or brain FC following real or sham rTMS stimuli in the DOC patients. However, real rTMS stimuli tended to enhance the FC of nodes in left lateral parietal cortex (LPC), left inferior temporal cortex (ITC) and right dorsolateral prefrontal cortex (DLPFC). (2). The individual analyses showed one minimally conscious state (MCS) patient presented with a obviously increased CRS-R score following real rTMS stimuli, and a visibly enhanced connectivity was observed in the nodes of left LPC, left ITC and right DLPFC of this patient.Conclusion: Our findings did not provide sufficient evidence of therapeutic effect of 20 Hz rTMS over the left M1 in DOC. However, MCS patients shortly after brain injury may possibly benefit from rTMS. Reconstruction of the left LPC, the left ITC and the right DLPFC may be the brain networking foundation of improvements in consciousness from rTMS.
Highlights
The term chronic disorders of consciousness (DOC) refers to the state of wakefulness without awareness or with minimal awareness in a patient following brain injury, including the unresponsive wakefulness syndrome/vegetative state (UWS/VS) and the minimally conscious state (MCS) [1]
High frequency repetitive TMS (rTMS) has lately been used in an attempt to treat DOC, with the stimulation points mostly positioned at the primary motor cortex (M1) or the dorsolateral prefrontal cortex (DLPFC)
By comparison with the healthy controls, the DOC patients demonstrated significantly altered Functional Connectivity (FC). Those DOC patients exhibited enhanced connections between the node of right lateral parietal cortex (LPC) and the left precentral gyrus/postcentral gyrus, in contrast, they had weakened connections between the node of left inferior temporal cortex (ITC) and the left cuneus/superior occipital gyrus, between the node of thalamus and the right medial frontal gyrus/anterior cingulate gyrus, between the node of left DLPFC and the left cerebellum posterior lobe
Summary
The term chronic disorders of consciousness (DOC) refers to the state of wakefulness without awareness or with minimal awareness in a patient following brain injury, including the unresponsive wakefulness syndrome/vegetative state (UWS/VS) and the minimally conscious state (MCS) [1]. Given its property of modulation, high frequency repetitive TMS (rTMS) increases the excitability of cortical neurons, whereas low frequency rTMS decreases their excitability These effects persist for a period following the stimulation [7]. Manganotti et al applied 20 Hz rTMS to the M1 region in 3 UWS/VS patients and 3 MCS patients and achieved significant behavioral improvement in one of the MCS patients, whose Coma Recovery Scale-Revised (CRS-R) score increased by 8 points and whose EEG persistently responded well [9]. In another randomized and sham-controlled EEG study conducted by Cincotta et al, there was no improvement of consciousness in UWS/VS patients following 20 Hz rTMS applied at the M1 region [10]
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