Electrophysiological Multimodal Assessments Improve Outcome Prediction in Traumatic Cervical Spinal Cord Injury.

Outcome prediction after spinal cord injury (SCI) is essential for early counseling and orientation of the rehabilitative intervention. Moreover, prognostication of outcome is crucial to achieving meaningful stratification when conceiving clinical trials. Neurophysiological examinations are commonly employed for prognostication after SCI, but whether neurophysiology could improve the functional prognosis based on clinical predictors remains an open question. Data of 224 patients included in the European Multicenter Study about Spinal Cord Injury were analyzed with bootstrapping analysis and multivariate logistical regression to derive prediction models of complete functional recovery in the chronic stage after traumatic cervical SCI. Within 40 days after SCI, we evaluated age, gender, the motor and sensory cumulative scores of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), and neurophysiological variables (motor evoked potentials, sensory evoked potentials, nerve conduction study) as possible predictors. Positive outcome was defined by a Spinal Cord Independence Measure total score of 100. Analyzing clinical variables, we derived a prediction model based on the ISNCSCI total motor score and age: the area under the receiver operating curve (AUC) was 0.936 (95% confidence interval [CI]: 0.904-0.968). Adding neurophysiological variables to the model, the AUC increased significantly: 0.956 (95% CI: 0.930-0.982; p = 0.019). More patients could be correctly classified by adding the electrophysiological data. Our study demonstrates that neurophysiological assessment improves the prediction of functional prognosis after traumatic cervical SCI, and suggests the use of neurophysiology to optimize patient information, rehabilitation, and discharge planning and the design of future clinical trials.

How specific are deficits in mismatch negativity generation to schizophrenia?

BACKGROUND: Mismatch negativity (MMN) is an auditory event-related potential that provides an index of auditory sensory memory. Deficits in MMN generation have been repeatedly demonstrated in chronic schizophrenia. Their specificity to schizophrenia has not been established. METHODS: Mismatch negativity to both duration and frequency deviants was investigated in gender- and age-matched patients with schizophrenia or schizoaffective disorder (n = 26), bipolar disorder (n = 16), or major depression (n = 22) and healthy control subjects (n = 25). RESULTS: Only patients with schizophrenia demonstrated significantly smaller mean MMN than did healthy control subjects. Detailed analyses showed significantly smaller MMN to both duration and frequency deviants in patients with schizophrenia than in healthy control subjects; however, the reduction of frequency MMN in patients with schizophrenia was not significant in the comparison across all groups. Mismatch negativity topography did not differ among groups. No consistent correlations with clinical, psychopathologic, or treatment variables were observed. CONCLUSIONS: Mismatch negativity deficits, and by extension deficits in early cortical auditory information processing, appear to be specific to schizophrenia. Animal and human studies implicate dysfunctional N-methyl-D-aspartate receptor functioning in MMN deficits. Thus MMN deficits may become a useful endophenotype to investigate the genetic underpinnings of schizophrenia, particularly with regard to the N-methyl-D-aspartate receptor.

Effects of the 5-HT2A agonist psilocybin on mismatch negativity generation and AX-continuous performance task: implications for the neuropharmacology of cognitive deficits in schizophrenia.

Previously the NMDA (N-methyl-D-aspartate) receptor (NMDAR) antagonist ketamine was shown to disrupt generation of the auditory event-related potential (ERP) mismatch negativity (MMN) and the performance of an 'AX'-type continuous performance test (AX-CPT)--measures of auditory and visual context-dependent information processing--in a similar manner as observed in schizophrenia. This placebo-controlled study investigated effects of the 5-HT(2A) receptor agonist psilocybin on the same measures in 18 healthy volunteers. Psilocybin administration induced significant performance deficits in the AX-CPT, but failed to reduce MMN generation significantly. These results indirectly support evidence that deficient MMN generation in schizophrenia may be a relatively distinct manifestation of deficient NMDAR functioning. In contrast, secondary pharmacological effects shared by NMDAR antagonists and the 5-HT(2A) agonist (ie disruption of glutamatergic neurotransmission) may be the mechanism underlying impairments in AX-CPT performance observed during both psilocybin and ketamine administration. Comparable deficits in schizophrenia may result from independent dysfunctions of 5-HT(2A) and NMDAR-related neurotransmission.

Mismatch negativity predicts psychotic experiences induced by NMDA receptor antagonist in healthy volunteers.

BACKGROUND: Previous studies indicate that mismatch negativity (MMN)-a preattentive auditory event-related potential (ERP)-depends on NMDA receptor (NMDAR) functioning. To explore if the strength of MMN generation reflects the functional condition of the NMDAR system in healthy volunteers, we analyzed correlations between MMN recorded before drug administration and subsequent responses to the NMDAR antagonist ketamine or the 5-HT2a agonist psilocybin. METHODS: In two separate studies, MMN was recorded to both frequency and duration deviants prior to administration of ketamine or psilocybin. Behavioral and subjective effects of ketamine and psilocybin were assessed with the Brief Psychiatric Rating Scale and the OAV Scale-a rating scale developed to measure altered states of consciousness. Correlations between ERP amplitudes (MMN, N1, and P2) and drug-induced effects were calculated in each study group and compared between them. RESULTS: Smaller MMN to both pitch and duration deviants was significantly correlated to stronger effects during ketamine, but not psilocybin administration. No significant correlations were observed for N1 and P2. CONCLUSIONS: Smaller MMN indicates a NMDAR system that is more vulnerable to disruption by the NMDAR antagonist ketamine. MMN generation appears to index the functional state of NMDAR-mediated neurotransmission even in subjects who do not demonstrate any psychopathology.