Clinical application of neuromodulation therapy in patients with disorder of consciousness: A pooled analysis of 544 participants.

BACKGROUND: The number of patients with disorders of consciousness (DoC) has increased dramatically with the advancement of intensive care and emergency medicine, which brings tremendous economic burdens and even ethical issues to families and society. OBJECTIVE: To evaluate the effectiveness of neuromodulation therapy for patients with DoC. METHODS: First, we conducted a literature review of individual patient data (IPD) on PubMed, EMBASE, and Cochrane-controlled trials following PRISMA guidelines. Then, we collected neuromodulation cases from our institution. Finally, we conducted a pooled analysis using the participants from the medical literature (n = 522) and our local institutions (n = 22). RESULTS: In this pooled analysis of 544 patients with DoC with a mean age of 46.33 years, our results revealed that patients have improved CRS-R scores [1.0 points (95% CI, 0.57-1.42)] after neuromodulation. Among them, patients have better effectiveness in traumatic than non-traumatic etiology (P < 0.05). The effectiveness of consciousness improvement could be affected by the age, baseline consciousness state, and duration of stimulation. Compared with non-invasive intervention, an invasive intervention can bring more behavioral improvement (P < 0.0001) to MCS rather than UWS/VS patients. Importantly, neuromodulation is a valuable therapy even years after the onset of DoC. CONCLUSION: This pooled analysis spotlights that the application of neuromodulation can improve the behavioral performance of patients with DoC. A preliminary trend is that age, etiology, baseline consciousness state, and stimulation duration could impact its effectiveness.

Assessing the depth of language processing in patients with disorders of consciousness.

Assessing residual consciousness and cognitive abilities in unresponsive patients is a major clinical concern and a challenge for cognitive neuroscience. Although neuroimaging studies have demonstrated a potential for informing diagnosis and prognosis in unresponsive patients, these methods involve sophisticated brain imaging technologies, which limit their clinical application. In this study, we adopted a new language paradigm that elicited rhythmic brain responses tracking the single-word, phrase and sentence rhythms in speech, to examine whether bedside electroencephalography (EEG) recordings can help inform diagnosis and prognosis. EEG-derived neural signals, including both speech-tracking responses and temporal dynamics of global brain states, were associated with behavioral diagnosis of consciousness. Crucially, multiple EEG measures in the language paradigm were robust to predict future outcomes in individual patients. Thus, EEG-based language assessment provides a new and reliable approach to objectively characterize and predict states of consciousness and to longitudinally track individual patients' language processing abilities at the bedside.

ISO-alpha-acids improve the hematoma resolution and prevent peri-hematoma inflammations by transforming microglia via PPARgamma-CD36 axis in ICH rats.

OBJECTIVE: To elucidate the effects of ISO-α-acids (IAAs), a PPAR-γ agonist, on ICH rats and its potential mechanism. MATERIAL AND METHODS: The Sprague Dawley rats ICH model was induced by stereotactic injecting of 100 µl autologous artery blood. Ninety male rats were randomly allocated to five groups: autologous blood and IAAs (IAA); received autologous blood, IAAs and PPAR-γ inhibitor (IAA + GW9662); autologous blood and normal Saline (Saline); only autologous blood (Mock); and only needle injection (Sham). Neurological functions were assessed by mNSS. Hematoma volume, brain water content, surface proteins and inflammatory factors were detected. The microglia anti-inflammatory abilities were also evaluated. RESULTS: IAAs were able to significantly decrease ICH rat's mNSS scores, alleviate brain water content, improve hematoma resolution than Saline, Mock (p < 0.05). More "M2" microglial/macrophage can be induced by IAAs. The expression of CD 36 was statistically higher in IAA than other groups (p < 0.05). Injection of IAAs led to a greatly increasing in CD 11b and CD 206 double-positive anti-inflammatory type microglial/macrophage, moreover, a reduction of inflammatory cytokines expression (p < 0.05). Such protective effects can be relieved by GW9662. CONCLUSIONS: This is the first study to elucidate the relationship between IAAs and ICH. IAAs were able to accelerate hematoma absorption, alleviate brain edema, suppress peri-hematoma inflammations and finally improved the outcome of ICH rats. The phenotype was due to the IAAs induction of "M2" microglial/macrophage via activating of PPAR-γ and increasing CD 36 expression.

The self and its resting state in consciousness: an investigation of the vegetative state.

Recent studies have demonstrated resting-state abnormalities in midline regions in vegetative state/unresponsive wakefulness syndrome and minimally conscious state patients. However, the functional implications of these resting-state abnormalities remain unclear. Recent findings in healthy subjects have revealed a close overlap between the neural substrate of self-referential processing and the resting-state activity in cortical midline regions. As such, we investigated task-related neural activity during active self-referential processing and various measures of resting-state activity in 11 patients with disorders of consciousness (DOC) and 12 healthy control subjects. Overall, the results revealed that DOC patients exhibited task-specific signal changes in anterior and posterior midline regions, including the perigenual anterior cingulate cortex (PACC) and posterior cingulate cortex (PCC). However, the degree of signal change was significantly lower in DOC patients compared with that in healthy subjects. Moreover, reduced signal differentiation in the PACC predicted the degree of consciousness in DOC patients. Importantly, the same midline regions (PACC and PCC) in DOC patients also exhibited severe abnormalities in the measures of resting-state activity, that is functional connectivity and the amplitude of low-frequency fluctuations. Taken together, our results provide the first evidence of neural abnormalities in both the self-referential processing and the resting state in midline regions in DOC patients. This novel finding has important implications for clinical utility and general understanding of the relationship between the self, the resting state, and consciousness.