Sex differences in symptom presentation and functional outcomes: a pilot study in a matched sample of veterans with mild TBI.

Primary Objective: Research focused on mild traumatic brain injury in active military and veteran populations details the psychological, neurological and functional outcomes of mTBI, in a primarily male (~95%) cohort. This may misrepresent female symptoms and outcomes. Here we assess for genuine sex differences in symptom presentation and functional outcomes.Research Design: We used matched pairs to preclude potential sex bias in outcome data.Methods and Procedures: We matched 49 female/male pairs on; 1) mechanism of injury, 2) time from injury to assessment and 3) age at assessment. Statistics were t-tests, chi-square, correlations and post hoc linear regression.Main outcomes and results: Outcome assessment revealed four significant (p < .05) sex differences; Living situation, Marital status, Vocation and Branch of service. Only the Neurobehavioral Symptom Inventory (NSI) composite cognitive domain factor was significantly different between females (mean: 10.26) and males (mean: 7.58). Linear regression confirmed a significant effect of sex for the cognitive composite (p = .002).Conclusion: We conclude that sex has a moderate effect on mTBI post-concussive symptom presentation. The significant sex difference in the NSI cognitive domain characterizes sex-related symptomology profiles providers can focus on for better rehabilitation management. Replication in the larger cohort would improve generalizability.Abbreviation: TBI: Traumatic Brain Injuries; mTBI: mild Traumatic Brain Injuries; OIF: Operation Iraqi Freedom; OEF: Operation Enduring Freedom; VA: Veterans Affairs Health Care System; PSC: Polytrauma System of Care; PRC: Polytrauma Rehabilitation Center; PTRP: Polytrauma Transitional Rehabilitation Program; PNS: Polytrauma Network Site; PTSD: Post Traumatic Stress Disorder; DoD: Department of Defense; NSI: Neurobehavioral Symptom Inventory; LOC: loss of consciousness; AOC: alteration of consciousness; PTA: posttraumatic amnesia; CPRS: computerized patient record system; CTBIE: Comprehensive TBI Evaluation; OCD: obsessive compulsive disorder; ETOH: alcohol abuse.

Long-Term Functional Outcomes in Military Service Members and Veterans After Traumatic Brain Injury/Polytrauma Inpatient Rehabilitation.

OBJECTIVE: To determine the effect of the established polytrauma/traumatic brain injury (TBI) infrastructure on immediate posttreatment functional gains, the long-term sustainability of any gains, and participation-related community reintegration outcomes in a baseline cohort of patients 8 years postadmission. DESIGN: Retrospective review and prospective repeated measures of an inception cohort. SETTING: Polytrauma rehabilitation center (PRC). PARTICIPANTS: Patients consecutively admitted to the PRC inpatient rehabilitation unit during its first full fiscal year, 2006 (N=44). INTERVENTIONS: The PRC infrastructure and formalized rehabilitation for polytrauma/TBI. MAIN OUTCOME MEASURES: FIM scores at admission, discharge, 3 months, and 8 years postdischarge; participation-related socioeconomic factors reflecting community reintegration 8 years after admission. RESULTS: Functional gains were statistically significantly increased from admission to discharge. Improvements were maintained at both 3 months postdischarge and 8 years postdischarge. The socioeconomic data collected at 8-year follow-up showed >50% either competitively employed or continuing their education and 100% living in a noninstitutionalized setting. CONCLUSIONS: This study addresses a concern regarding the long-term functional outcomes of rehabilitation patients treated by the established infrastructure of the Polytrauma System of Care inpatient rehabilitation centers. The results suggest that polytrauma/TBI rehabilitation care using a comprehensive, integrated approach is effective and durable in achieving functional gains and successful community reintegration within our initial PRC cohort. Follow-up of subsequent fiscal year cohorts would add to the validity of these outcome findings.

Relationship of imprecise corollary discharge in schizophrenia to auditory hallucinations.

CONTEXT: A forward model of intended thoughts and actions prepares sensory cortex for sensations that are a consequence of those actions. Imprecision of the corollary discharge in schizophrenia may contribute to the misperception of inner experiences and thoughts as "voices" or auditory hallucinations. OBJECTIVES: To assess the precision of the forward model in schizophrenia using the N100 component of the auditory event-related potential to speech that is altered or unaltered, in real time, as it is being spoken. To assess the relationship between auditory hallucinations and the imprecision of the corollary discharge. DESIGN: Prospective case-control study. SETTING: Community mental health centers and Palo Alto Veterans Affairs Health Care System, Palo Alto, Calif. PARTICIPANTS: Twenty patients with schizophrenia and 17 sex- and age-matched healthy control subjects. MAIN OUTCOME MEASURES: N100 responses to auditory feedback, which was altered by pitch-shifting the self-voice, substituting an alien voice, or pitch-shifting the alien voice. On each trial, subjects judged whether feedback was "self," "other," or "unsure." Clinical ratings were used to assess severity of auditory hallucinations in patients. RESULTS: In controls, N100 to unaltered self-voice feedback was dampened relative to N100 to altered self-voice or alien auditory feedback. This pattern was not seen in hallucinating patients. This imprecision correlated with the severity of hallucinations and with the percentage of misattribution errors. CONCLUSION: These data support a connection between auditory verbal hallucinations and the imprecision of the corollary discharge heralding the sensory consequences of thoughts and actions.

Temporal stability of auditory event-related potentials in healthy individuals and patients with traumatic brain injury.

Historically, cognitive event-related potentials (ERPs) have received limited acceptance for clinical use due to lack of evidence for their reliability. However, recent advances in computer technology and artifact rejection methods have greatly enhanced the fidelity of ERP measurements. The present study examined the test-retest reliability of ERP measurement by using current data processing methods. We assessed the temporal stability of the most commonly used ERP paradigm, auditory pure-tone "odd ball" detection, and compared it with other commonly used clinical measures reported in the literature. Auditory ERPs were collected in 19 healthy subjects and 7 patients with traumatic brain injury at two time points, 2 days to 2 months apart. Test-retest reliability was calculated for four ERP components: N1, MMN (mismatch negativity), P3, and N4. In healthy subjects, temporal stabilities of these four commonly studied ERP components' amplitude measurements were moderate to high, with intraclass correlations ranging from 0.6 to 0.8. In contrast, in patients with traumatic brain injury, ERPs were stable only for the N1 component (intraclass correlation = 0.7).

The effects of increasing stimulus complexity in event-related potentials and reaction time testing: clinical applications in evaluating patients with traumatic brain injury.

This study compared the effectiveness of P300 event related potentials (ERPs) and reaction time (RT) in discriminating patients with traumatic brain injury (TBI) from healthy control subjects. In particular, we examined how the use of more complex, ecologically relevant stimuli may affect the clinical utility of these tasks. We also evaluated how length of posttraumatic amnesia (PTA) and loss of consciousness (LOC) related to P300 and RT measures in our patient sample. There were 22 subjects (11 patients with TBI and 11 age-matched healthy control subjects). Four stimulus detection procedures were used: two using simple, conventional stimuli (auditory tone discrimination, AT; visual color discrimination, VC), and two using complex, ecologically relevant stimuli in the auditory and visual modalities (auditory word category discrimination, AWC; visual facial affect discrimination, VFA). Our results showed that RT measures were more effective in identifying TBI patients when complex stimuli were used (AWC and VFA). On the other hand, ERP measures were more effective in identifying TBI patients when simple stimuli were used (AT and VC). We also found a remarkably high correlation between duration of PTA and P300 amplitude.

Health Coaching: A Preliminary Report on the Effects in Traumatic Brain Injury/Polytrauma Patients.

BACKGROUND: Failure to adhere to treatment recommendations has significant impact on the health outcomes of the individual and health care systems. Health coaching is a promising care model that has gained interest in the medical field. This study focused on the impact of health coaching on health behaviors that may have direct impact on successful patient outcomes. PRIMARY STUDY OBJECTIVE: The objective of this study was to assess the impact of health coaching administered through the Polytrauma Integrative Medicine Initiative (PIMI). METHODS/DESIGN: This study was a quasiexperimental cohort study. SETTING: This study occurred at a specialized polytrauma rehabilitation center. PARTICIPANTS: Participants were divided into 3 cohorts: (1) 33 patients who served through PIMI enrollment, (2) 22 patients who declined PIMI, and (3) a control cohort of 30 random patients who were not referred to PIMI. Patients were primarily male active duty or veteran military personnel. INTERVENTION: The intervention consisted of personalized health coaching by trained, certified personnel. PRIMARY OUTCOME MEASURES: Outcome measures included the following (1) Self-assessment: utilizing the Personal Health Inventory (PHI) at enrollment and at 3 mo; (2) treatment adherence: the percentage of scheduled appointments fulfilled by patients; and (3) post hoc analysis: for no-show and cancellation rates; 2-tailed paired t tests for PHI data and post hoc within groups; 2-tailed independent samples t tests for treatment adherence percentages and post hoc between groups. RESULTS: There was no significant difference in treatment adherence rates between the 3 cohorts (all P > .45). PIMI patients had significantly higher cancellation rates than no-show rates for both clinical, 20.8%/5%, and coaching appointments, 17.3%/7.5%, (P < .05). PIMI patients had significantly lower no-show rates, 5%, than control patients, 15.8% (P = .007). PHI data suggest PIMI patients believe they are making improvements in many areas of health coaching focus. CONCLUSION: Low cohort numbers are a concern. There was no difference for treatment adherence rates for health coaching compared with no health coaching. Select variables such as cancellation and no-show appointment rates may better capture the impact of health coaching on patient behavior and clinical resource utilization.

Acquiring and inhibiting prepotent responses in schizophrenia: event-related brain potentials and functional magnetic resonance imaging.

BACKGROUND: Schizophrenia is associated with deficits in using context to establish prepotent responses in complex paradigms and failures to inhibit prepotent responses once established. OBJECTIVE: To assess prepotent response establishment and inhibition in patients with schizophrenia using event-related brain potential (ERP) and functional magnetic resonance imaging (fMRI) in a simple NoGo task. To combine fMRI and ERP data to focus on fMRI activations associated with the brief (approximately 200 ms) moment of context updating reflected in the NoGo P300 ERP component. DESIGN AND SETTING: We collected ERP and fMRI data while subjects performed a NoGo task requiring a speedy button press to X stimuli (P=.88) but not to K stimuli (P=.12). The ERPs were collected at the Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif; fMRIs were collected at Stanford University, Stanford, Calif. PARTICIPANTS: We recruited patients with DSM-IV schizophrenia (n=11) from the community and the VA hospital and sex- and age-matched healthy control subjects (n=11) from the community. MAIN OUTCOME MEASURES: Behavioral accuracy, P300 amplitudes and latencies, and fMRI activations suggested that patients with schizophrenia did not establish as strong a prepotent tendency to respond to the Go stimulus as healthy subjects. In healthy subjects, NoGo P300 was related to activations in the anterior cingulate cortex, dorsal lateral prefrontal cortex, and right inferior parietal lobule and caudate nucleus, perhaps reflecting conflict experienced when withholding a response, control needed to inhibit a response, and stopping a response in action, respectively. In patients with schizophrenia, NoGo P300 was modestly related to activations in the anterior cingulate cortex, which is consistent with experiencing conflict. CONCLUSIONS: The difference in ERP and fMRI responses to Go and NoGo stimuli suggested that inhibiting a response was easier for patients with schizophrenia than for healthy subjects. Correlations of P300 and fMRI data suggested that patients with schizophrenia and healthy subjects used different neural structures to inhibit responses, with healthy subjects using a more complex system.

Reduced gamma-band coherence to distorted feedback during speech when what you say is not what you hear.

BACKGROUND: Communication between the frontal lobes, where speech is generated, and the temporal lobes, where it is perceived, may occur through the action of an efference copy/corollary discharge mechanism that prepares the temporal lobes for the expected sound. We suggest that coherence of EEG in gamma-band between frontal and temporal lobes may reflect the successful action of such a mechanism. We tested the hypothesis that there would be a disruption of gamma-band coherence when the expected auditory consequence of speech does not match the auditory experience. METHOD: EEG was recorded from 21 healthy adult subjects as they uttered the sound [a:] (Talking condition) and as they heard these recorded sounds played back (Listening condition). As they spoke, subjects heard real-time feedback of the sounds that were: (1) pitch-shifted down one semi-tone, (2) pitch-shifted down one-half of a semi-tone, or (3) not pitch-shifted (veridical), each in separate runs. Event-related gamma coherence between frontal and temporal sites was calculated relative to the onset of the sound, as it was being spoken during Talking, and as it was being played back during Listening. RESULTS: Frontal-temporal gamma-band coherence spanning 33-43 Hz was greater during Talking than Listening and greater when speech was veridical than when it was distorted a whole semi-tone. CONCLUSIONS: Gamma-band fronto-temporal synchrony may reflect a "binding of expectation with experience." Disruption of this synchrony may provide feedback to the frontal lobes, particularly regions subserving vocalization, to implement sensorimotor adaptations to either adjust motor programs for speech production in the short run, or to reorganize expectations in the long run.

Response-monitoring dysfunction in schizophrenia: an event-related brain potential study.

Error-monitoring abnormalities may underlie positive symptoms of schizophrenia. Response-synchronized event-related potentials during picture-word matching yielded error- and correct-response-related negativity (ERN, CRN) and positivity (Pe, Pc) and preresponse lateralized readiness potentials (LRP) from 18 schizophrenic patients and 18 controls. Both groups responded faster to matches than nonmatches, although patients were generally slower and made more errors to nonmatches. Compared with controls, patients, particularly with paranoid subtype, had smaller ERNs and larger CRNs, which were indistinguishable. LRPs showed evidence of more response conflict before errors than before correct responses in controls but not patients. Despite ERN/CRN abnormalities, post-error slowing and Pe were normal in patients, suggesting a dissociation of ERN and error awareness. Anterior cingulate and dorsolateral prefrontal cortical dysfunction in schizophrenia are implicated.

Simultaneous measurement of perceptual and motor cortical potentials: implications for assessing information processing in traumatic brain injury.

OBJECTIVE: Psychomotor slowing is a common manifestation of traumatic brain injury. Previous electrophysiological studies of traumatic brain injury have focused on abnormal attentional and perceptual responses to incoming stimuli. We hypothesize that traumatic brain injury is also associated with abnormal cortical components of motor execution. DESIGN: To test this hypothesis, we analyzed event-related potentials of 22 subjects (11 with a history of severe traumatic brain injury and 11 age-matched healthy subjects) during oddball discrimination tasks. In addition to the usual stimulus-locked averaging of electrophysiological data to reveal cognitive components, such as the P300, we also analyzed subjects' response-locked data to reveal motor potential waveforms. To focus on generalized effects across modality, analyses were performed on composite measures from both auditory and visual event-related potentials. RESULTS: (1) Traumatic brain injury subjects had abnormal P300 responses (with reduced amplitude and prolonged latency) in both sensory modalities. (2) Traumatic brain injury subjects' motor potential waveforms showed significantly reduced amplitude in both sensory modalities. (3) Abnormalities in P300 latency, amplitude, and motor potential amplitude (effect sizes = 1.2-1.5 SD) were greater than behavioral slowing, as measured by reaction times (0.7 SD). (4) P300 latency and motor potential amplitude together accounted for much of the reaction time prolongation (r = 0.73). CONCLUSIONS: This study demonstrates the value of concurrently analyzing stimulus-locked and response-locked event-related potential data to evaluate cortical components of perceptual and motor processing. The present findings indicate that patients with traumatic brain injury have impairments in both the perceptual interpretation of incoming stimuli and the execution of motor responses and that both abnormalities contribute to psychomotor slowing in patients with traumatic brain injury.

Dissecting corollary discharge dysfunction in schizophrenia.

During talking, a corollary discharge prepares cortex for self-generated sounds, minimizing responsiveness and providing a way to recognize sounds as self-generated. When we talk, we are the agent producing the sound and know what sound to expect. The auditory ERP N1 is normally suppressed during talking, but less so in schizophrenia, perhaps due to deficits in agency and expectancy inherent to talking. N1 was assessed in 27 patients (23 schizophrenia, 4 schizoaffective) and 26 controls. During talking, subjects said "ah" every 1-2 s. During agency, subjects pressed a button to deliver "ah" every 1-2 s. During expectancy, "ah" followed a visual warning. Talking yielded greatest N1 suppression in controls and greatest suppression failure in patients. Agency and expectancy had modest suppression effects on N1 and only in controls. Group differences in expectancy and agency could not account for failed corollary discharge during talking in patients.

Prognostic value of evoked and event-related potentials in moderate to severe brain injury.

Clinicians are often expected to project patients' clinical outcomes to allow effective planning for future care. This can be a challenge in patients with moderate to severe traumatic brain injury (TBI) who are often unable to participate reliably in clinical evaluations. With recent advances in computer instrumentation and signal processing, evoked potentials and event-related potentials show increasing promise as powerful tools for prognosticating the trajectory of recovery and ultimate outcome from the TBI. Short- and middle-latency evoked potentials can now effectively predict coma outcomes in patients with acute TBI. Long-latency event-related potential components hold promise in predicting recovery of higher order cognitive abilities.

Fine-tuning of auditory cortex during speech production.

The cortex suppresses sensory information when it is the result of a self-produced motor act, including the motor act of speaking. The specificity of the auditory cortical suppression to self-produced speech, a prediction derived from the posited operation of a precise forward model system, has not been established. We examined the auditory N100 component of the event-related brain potential elicited during speech production. While subjects uttered a vowel, they heard real-time feedback of their unaltered voice, their pitch-shifted voice, or an alien voice substituted for their own. The subjects' own unaltered voice feedback elicited a dampened auditory N100 response relative to the N100 elicited by altered or alien auditory feedback. This is consistent with the operation of a precise forward model modulating the auditory cortical response to self-generated speech and allowing immediate distinction of self and externally generated auditory stimuli.