Stability of mismatch negativity event-related potentials in a multisite study.

OBJECTIVES: Mismatch negativity (MMN), an auditory event-related potential sensitive to deviance detection, is smaller in schizophrenia and psychosis risk. In a multisite study, a regression approach to account for effects of site and age (12-35 years) was evaluated alongside the one-year stability of MMN. METHODS: Stability of frequency, duration, and frequency + duration (double) deviant MMN was assessed in 167 healthy subjects, tested on two occasions, separated by 52 weeks, at one of eight sites. Linear regression models predicting MMN with age and site were validated and used to derive standardized MMN z-scores. Variance components estimated for MMN amplitude and latency measures were used to calculate Generalizability (G) coefficients within each site to assess MMN stability. Trait-like aspects of MMN were captured by averaging across occasions and correlated with subject traits. RESULTS: Age and site accounted for less than 7% of MMN variance. G-coefficients calculated at electrode Fz were stable (G = 0.63) across deviants and sites for amplitude measured in a fixed window, but not for latency (G = 0.37). Frequency deviant MMN z-scores averaged across tests negatively correlated with averaged global assessment of functioning. CONCLUSION: MMN amplitude is stable and can be standardized to facilitate longitudinal multisite studies of patients and clinical features.

Clinical and Cognitive Significance of Auditory Sensory Processing Deficits in Schizophrenia.

OBJECTIVE: Although patients with schizophrenia exhibit impaired suppression of the P50 event-related brain potential in response to the second of two identical auditory stimuli during a paired-stimulus paradigm, uncertainty remains over whether this deficit in inhibitory gating of auditory sensory processes has relevance for patients' clinical symptoms or cognitive performance. The authors examined associations between P50 suppression deficits and several core features of schizophrenia to address this gap. METHOD: P50 was recorded from 52 patients with schizophrenia and 41 healthy comparison subjects during a standard auditory paired-stimulus task. Clinical symptoms were assessed with the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms. The MATRICS Consensus Cognitive Battery was utilized to measure cognitive performance in a subsample of 39 patients. Correlation and regression analyses were conducted to examine P50 suppression in relation to clinical symptom and cognitive performance measures. RESULTS: Schizophrenia patients demonstrated a deficit in P50 suppression when compared with healthy subjects, replicating prior research. Within the patient sample, impaired P50 suppression covaried reliably with greater difficulties in attention, poorer working memory, and reduced processing speed. CONCLUSIONS: Impaired suppression of auditory stimuli was associated with core pathological features of schizophrenia, increasing confidence that P50 inhibitory processing can inform the development of interventions that target cognitive impairments in this chronic and debilitating mental illness.

Electrophysiological Endophenotypes for Schizophrenia.

Endophenotypes are quantitative, heritable traits that may help to elucidate the pathophysiologic mechanisms underlying complex disease syndromes, such as schizophrenia. They can be assessed at numerous levels of analysis; here, we review electrophysiological endophenotypes that have shown promise in helping us understand schizophrenia from a more mechanistic point of view. For each endophenotype, we describe typical experimental procedures, reliability, heritability, and reported gene and neurobiological associations. We discuss recent findings regarding the genetic architecture of specific electrophysiological endophenotypes, as well as converging evidence from EEG studies implicating disrupted balance of glutamatergic signaling and GABAergic inhibition in the pathophysiology of schizophrenia. We conclude that refining the measurement of electrophysiological endophenotypes, expanding genetic association studies, and integrating data sets are important next steps for understanding the mechanisms that connect identified genetic risk loci for schizophrenia to the disease phenotype.

Procedural Variations in the Stroop and the Symbol Digit Modalities Test: impact on patients with multiple sclerosis.

Decreased information processing speed is often cited as the primary cognitive deficit occurring in conjunction with multiple sclerosis (MS). Two common tools for assessing this deficit are the Stroop Test and the Symbol Digit Modalities Test (SDMT). However, there are procedural variations in these rapid serial processing (RSP) tests pertaining to the response format (e.g., verbal or manual) and the administration format (e.g., paper-based or computerized). The present study was designed to assess whether such variations impact MS patients' and healthy individuals' performance on these tests. In Experiment 1, we showed that response formats in which either the experimenter or the participant was responsible for advancing the items on computerized versions of the Stroop Test and the SDMT were basically equivalent in terms of distinguishing between patients and controls. In Experiment 2, we found differences between administration formats that appear to interact with some of the disease-related features of MS. Understanding how procedural variations differentially impact patients and controls can be useful for interpreting what RSP tests reveal about the cognitive impact of MS.

Mild traumatic brain injury from primary blast vs. blunt forces: post-concussion consequences and functional neuroimaging.

INTRODUCTION: Primary blast forces may cause dysfunction from mild traumatic brain injury (mTBI). OBJECTIVE: To investigate the effects of primary blast forces, independent of associated blunt trauma and post-traumatic stress disorder, on sensitive post-concussive measures. METHODS: This study investigated post-concussive symptoms, functional health and well-being, cognition, and positron emission tomography (PET) neuroimaging among 12 Iraq or Afghanistan war veterans who sustained pure blast-force mTBI, compared to 12 who sustained pure blunt-force mTBI. RESULTS: Both groups had significantly lower scores than published norms on the Rivermead Post-Concussion Questionnaire (RPQ) and the SF36-V Health Survey. Compared to the Blunt Group, the Blast Group had poorer scores on the Paced Auditory Serial Addition Test (PASAT) and greater PET hypometabolism in the right superior parietal region. Only the Blast Group had significant correlations of their RPQ, SF36-V Mental Composite Score, and PASAT scores with specific regional metabolic changes. CONCLUSION: This pilot study suggests that pure blast force mTBI may have greater post-concussive sequelae including deficits in attentional control and regional brain metabolism, compared to blunt mTBI. A disturbance of a right parietal-frontal attentional network is one potential explanation for these findings.

Difficulties in planning among patients with multiple sclerosis: a relative consequence of deficits in information processing speed.

Previous studies show that MS patients take longer than healthy controls to plan their solutions to Tower of London (TOL) problems but yield conflicting results regarding the quality of their solutions. The present study evaluated performance under untimed or timed conditions to assess the possibility that differences in planning ability only occur when restrictions in solution times are imposed. MS patients (n = 39) and healthy controls (n = 43) completed a computerized version of the TOL under one of two conditions. In the untimed condition, participants were allowed as much time as needed on each problem. In the timed condition, limits were imposed on solution times and time remaining was displayed with each problem. Patients exhibited longer planning times than controls, and the disparity between groups increased with problem difficulty. Planning performance depended upon condition. In the untimed condition, patients and controls performed equally well. When solution times were restricted, however, patients solved fewer problems than controls. MS patients' planning ability is intact when permitted sufficient time to formulate the required plan. Deficiencies in planning are only evident when time is restricted, and, therefore, are more accurately considered a relative consequence of disease-related problems in information processing speed.

Changes in personality after mild traumatic brain injury from primary blast vs. blunt forces.

INTRODUCTION: Injuries from explosive devices can cause blast-force injuries, including mild traumatic brain injury (mTBI). OBJECTIVE: This study investigated changes in personality from blast-force mTBI in comparison to blunt-force mTBI. METHODS: Clinicians and significant others assessed US veterans who sustained pure blast-force mTBI (n = 12), as compared to those who sustained pure blunt-force mTBI (n = 12). Inclusion criteria included absence of any mixed blast-blunt trauma and absence of post-traumatic stress disorder. Measures included the Interpersonal Measure of Psychopathy (IM-P), the Big Five Inventory (BFI), the Interpersonal Adjectives Scale (IAS) and the Frontal Systems Behaviour Scale (FrSBe). RESULTS: There were no group differences on demographic or TBI-related variables. Compared to the Blunt Group, the Blast Group had more psychopathy on the IM-P, with anger, frustration, toughness and boundary violations and tended to more neuroticism on the BFI. When pre-TBI and post-TBI assessments were compared on the IAS and FrSBe, only the patients with blast force mTBI had become more cold-hearted, aloof-introverted and apathetic. CONCLUSION: These results suggest that blast forces alone can cause negativistic behavioural changes when evaluated with selected measures of personality. Further research on isolated blast-force mTBI should focus on these personality changes and their relationship to blast over-pressure.

Deficits in planning time but not performance in patients with multiple sclerosis.

Studies of planning ability typically involve some version of the Tower of Hanoi or Tower of London (TOL). When these tests are administered to patients with multiple sclerosis (MS), the findings pertaining to planning "performance" have been conflicting. Possible reasons for failures to find deficits in planning performance among MS patients are: (a) the patients typically have relapsing-remitting MS (RRMS) of mild severity and short duration and thus little cognitive impairment relative to those with more advanced disease; (b) the problems composing the tests are too simple and differences between patients and controls are therefore obscured by ceiling effects; and (c) the scoring system typically used permits participants to earn points for successful solutions on later trials after failing the initial attempt on each problem, thereby further diluting the difference between patients and controls. The present study compared the performance of patients with both relapsing-remitting and secondary progressive disease with that of healthy controls on a more challenging version of the TOL. Patients exhibited lengthier planning times on the test, greater disparity in their average planning times from those of controls as the difficulty level increased, and greater individual variability in their planning times across the full set of problems. However, no differences in planning performance were found between patients and controls or between RRMS and secondary progressive MS patients. Performance differences in other studies may be attributable in part to the imposition of time limits for solving each problem and the disproportionately adverse effect such time limits have on patients' performance.