P3a amplitude to trauma-related stimuli reduced after successful trauma-focused PTSD treatment.

An elevated P3a amplitude to trauma-related stimuli is strongly associated with posttraumatic stress disorder (PTSD), yet little is known about whether this response to trauma-related stimuli is affected by treatment that decreases PTSD symptoms. As an analysis of secondary outcome measures from a randomized controlled trial, we investigated the latency and amplitude changes of the P3a in responses in a three-condition oddball visual task that included trauma-related (combat scenes) and trauma-unrelated (threatening animals) distractors. Fifty-five U.S. veterans diagnosed with combat-related PTSD were randomized to receive either active or sham repetitive transcranial magnetic stimulation (rTMS). All received cognitive processing therapy, CPT+A, which requires a written account of the index trauma. They were tested before and 6 months after protocol completion. P3a amplitude and response time decreases were driven largely by the changes in the responses to the trauma-related stimuli, and this decrease correlated to the decrease in PTSD symptoms. The amplitude changes were greater in those who received rTMS + CPT than in those who received sham rTMS + CPT, suggesting that rTMS plays beneficial role in reducing arousal and threat bias, which may allow for more effective engagement in trauma-focused PTSD treatment.

Auditory N2 Correlates of Treatment Response in Posttraumatic Stress Disorder.

Emotional processing and cognitive control are implicated as being dysfunctional in posttraumatic stress disorder (PTSD) and targeted in cognitive processing therapy (CPT), a trauma-focused treatment for PTSD. The N2 event-related potential has been interpreted in the context of emotional processing and cognitive control. In this analysis of secondary outcome measures from a randomized controlled trial, we investigated the latency and amplitude changes of the N2 in responses to task-relevant target tones and task-irrelevant distractor sounds (e.g., a trauma-related gunshot and a trauma-unrelated lion's roar) and the associations between these responses and PTSD symptom changes. United States military veterans (N = 60) diagnosed with combat-related PTSD were randomized to either active or sham repetitive transcranial magnetic stimulation (rTMS) and received a CPT intervention that included a written trauma account element (CPT+A). Participants were tested before and 6 months after protocol completion. Reduction in N2 amplitude to the gunshot stimulus was correlated with reductions in reexperiencing, |r| = .445, and hyperarousal measures, |r| = .364. In addition, in both groups, the latency of the N2 event-related potential to the distractors became longer with treatment and the N2 latency to the task-relevant stimulus became shorter, ηp 2  = .064, both of which are consistent with improved cognitive control. There were no between-group differences in N2 amplitude and latency. Normalized N2 latencies, reduced N2 amplitude to threatening distractors, and the correlation between N2 amplitude reduction and PTSD symptom reduction reflect improved cognitive control, consistent with the CPT+A objective of addressing patients' abilities to respond more appropriately to trauma triggers.

Neurophysiology of threat processing bias in combat-related post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a debilitating condition that may develop after experiencing a traumatic event. Combat exposure increases an individual's chance of developing PTSD, making veterans especially susceptible to the disorder. PTSD is characterized by dysregulated emotional networks, memory deficits, and a hyperattentive response to perceived threatening stimuli. Recently, there have been a number of imaging studies that show structural and functional abnormalities associated with PTSD; however, there have been few studies utilizing electroencephalography (EEG). The goal of this study was to characterize **EEG brain dynamics in individuals with PTSD, in order to better understand the neurophysiological underpinnings of some of the salient features of PTSD, such as threat-processing bias. Veterans of Operation Enduring Freedom/Iraqi Freedom completed an implicit visual threat semantic memory recognition task with stimuli that varied on both category (animals, items, nature, and people) and feature (threatening and nonthreatening) membership, including trauma-related stimuli. Combat veterans with PTSD had slower reaction times for the threatening stimuli relative to the combat veterans without PTSD (VETC). There were trauma-specific effects in frontal regions, with theta band EEG power reductions for the threatening combat scenes in the PTSD patients compared to the VETC group. Additionally, a moderate negative correlation was observed between trauma-specific frontal theta power and hyperarousal symptoms as measured by clinically administered PTSD scale. These findings complement and extend current models of cortico-limbic dysfunction in PTSD. The moderate negative correlation between frontal theta power and hyperarousal endorsements suggests the utility of these measures as therapeutic markers of symptomatology in PTSD patients.

Gulf War illness associated with abnormal auditory P1 event-related potential: Evidence of impaired cholinergic processing replicated in a national sample.

Our team previously reported event-related potential (ERP) and hyperarousal patterns from a study of one construction battalion of the U.S. Naval Reserve who served during the 1991 Persian Gulf War. We sought to replicate these findings in a sample that was more representative of the entire Gulf War-era veteran population, including male and female participants from four branches of the military. We collected ERP data from 40 veterans meeting Haley criteria for Gulf War syndromes 1-3 and from 22 matched Gulf War veteran controls while they performed an auditory oddball task. Reports of hyperarousal from the ill veterans were significantly greater than those from the control veterans, and P1 amplitudes in Syndromes 2 and 3 were significantly higher than P1 amplitudes in Syndrome 1, replicating our previous findings. Many of the contributors to the generation of the P1 potential are also involved in the regulation of arousal and are modulated by cholinergic and dopaminergic systems-two systems whose dysfunction has been implicated in Gulf War illness. These differences among the three syndrome groups where their means were on either side of controls is a replication of our previous ERP study and is consistent with previous imaging studies of this population.

Conjoint differences in inhibitory control and processing speed in childhood to older adult cohorts: Discriminant functions from a Go/No-Go task.

To investigate differences in inhibitory control and processing speed over the life span, participants in 7- to 8-, 10- to 11-, 12- to 15-, 18- to 25-, and 54- to 80-year-old age cohorts completed a Go/No-Go task requiring varying levels of semantic categorization. Discriminant function analysis of correct rejection rates (CRRs), hit rates (HRs), and reaction times (RTs) revealed a function on which CRR loaded positively and RT loaded negatively, across categorization levels. Scores increased from youngest to the younger adult cohort and decreased for the older adult cohort. On a second function, CRR and RT loaded positively and HR loaded negatively across categorization levels. Scores were highest for the older adult cohort and higher for the youngest cohort than for the younger adult cohort. The results suggest change along 2 dimensions might underlie cognitive development: (a) combined increased inhibitory control and processing speed and (b) combined increased speed and decreased biased responding for better inhibitory control. In addition, 2 dimensions might underlie senescence: (a) combined decreased inhibitory control and processing speed and (b) combined decreased speed and increased biased responding for better inhibitory control. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Electrophysiological correlates of semantic memory retrieval in Gulf War Syndrome 2 patients.

Gulf War veterans meeting criteria for Haley Syndrome 2 of Gulf War illness endorse a particular constellation of symptoms that include difficulty with processing information, word-finding, and confusion. To explore the neural basis of their word-finding difficulty, we assessed event-related potentials (ERPs) associated with semantic memory retrieval in 22 veterans classified as Syndrome 2 and 28 veterans who served as controls. We recorded EEGs while subjects judged whether pairs of words that represented object features combined to elicit a retrieval of an object memory or no retrieval. Syndrome 2 subjects' responses were significantly slower, and those participants were less accurate than controls on the retrieval trials, but they performed similarly on the nonretrieval trials. Analysis of the ERPs revealed a difference between retrievals and nonretrievals that has previously been detected around 750ms at the left temporal region was present in both the Syndrome 2 patients and controls. However, the Syndrome 2 patients also showed an ERP difference between retrievals and nonretrievals at the midline parietal region that had a scalp voltage polarity opposite from that recorded at the left temporal area. We hypothesize that the similarities between task performance and ERP patterns in Syndrome 2 veterans and in patients with amnestic mild cognitive impairment reflect disordered thalamic cholinergic neural activity, possibly in the dorsomedial nucleus.

Visual event-related potentials as markers of hyperarousal in Gulf War illness: evidence against a stress-related etiology.

An exaggerated response to emotional stimuli is among the many symptoms widely reported by veterans of the 1991 Persian Gulf War. These symptomologies have been attributed to damage and dysfunction associated with deployment-related exposures. We collected event-related potential data from 22 veterans meeting Haley criteria for Gulf War (GW) Syndromes 1-3 and from 8 matched GW veteran controls, who were deployed but not symptomatic, while they performed a visual three-condition oddball task where images authenticated to be associated with the 1991 Persian Gulf War were the distractor stimuli. Hyperarousal reported by ill veterans was significantly greater than that by control veterans, but this was not paralleled by higher amplitude P3a in their ERP responses to GW-related distractor stimuli. Whereas previous studies of PTSD patients have shown higher amplitude P3b responses to target stimuli that are placed amid trauma-related nontarget stimuli, ill veterans in this study showed P3b amplitudes to target stimuli - placed amid GW-related nontarget stimuli - that were significantly lower than those of the control group. Hyperarousal scores reliably predicted P3b, but not P3a, amplitudes. Although many factors may contribute to P3b amplitude differences - most notably depression and poor sleep quality, symptoms that are prevalent in the GW syndrome groups - our findings in context of previous studies on this population are consistent with the contention that dysfunction in cholinergic and dopaminergic neurotransmitter systems, and in white matter and basal ganglia may be contributing to impairments in GW veterans.

Event-related potential patterns associated with hyperarousal in Gulf War illness syndrome groups.

An exaggerated response to emotional stimuli is one of the several symptoms widely reported by veterans of the 1991 Persian Gulf War. Many have attributed these symptoms to post-war stress; others have attributed the symptoms to deployment-related exposures and associated damage to cholinergic, dopaminergic, and white matter systems. We collected event-related potential (ERP) data from 20 veterans meeting Haley criteria for Gulf War Syndromes 1-3 and from 8 matched Gulf War veteran controls, who were deployed but not symptomatic, while they performed an auditory three-condition oddball task with gunshot and lion roar sounds as the distractor stimuli. Reports of hyperarousal from the ill veterans were significantly greater than those from the control veterans; different ERP profiles emerged to account for their hyperarousability. Syndromes 2 and 3, who have previously shown brainstem abnormalities, show significantly stronger auditory P1 amplitudes, purported to indicate compromised cholinergic inhibitory gating in the reticular activating system. Syndromes 1 and 2, who have previously shown basal ganglia dysfunction, show significantly weaker P3a response to distractor stimuli, purported to indicate dysfunction of the dopaminergic contribution to their ability to inhibit distraction by irrelevant stimuli. All three syndrome groups showed an attenuated P3b to target stimuli, which could be secondary to both cholinergic and dopaminergic contributions or disruption of white matter integrity.

Tracking cognitive phases in analogical reasoning with event-related potentials.

Analogical reasoning consists of multiple phases. Four-term analogies (A:B::C:D) have an encoding period in which the A:B pair is evaluated prior to a mapping phase. The electrophysiological timing associated with analogical reasoning has remained unclear. We used event-related potentials to identify neural timing related to analogical reasoning relative to perceptual and semantic control conditions. Spatiotemporal principal-components analyses revealed differences primarily in left frontal electrodes during encoding and mapping phases of analogies relative to the other conditions. The timing of the activity differed depending upon the phase of the problem. During the encoding of A:B terms, analogies elicited a positive deflection compared to the control conditions between 400 and 1,200 ms, but for the mapping phase analogical processing elicited a negative deflection that occurred earlier and for a shorter time period, between 350 and 625 ms. These results provide neural and behavioral evidence that 4-term analogy problems involve a highly active evaluation phase of the A:B pair.

Repetitive transcranial magnetic stimulation and threat memory: selective reduction of combat threat memory p300 response after right frontal-lobe stimulation.

Using the event-related potential P3a component as a marker, the authors tested the efficacy of repetitive transcranial magnetic stimulation (rTMS) for reducing hyperarousability to specific threat stimuli in one Vietnam veteran with chronic posttraumatic stress disorder (PTSD), who exhibited an exaggerated P3a response to combat-related pictures. Twenty minutes of 1-Hz rTMS to the right prefrontal area effected a reduction in the P3a amplitude, whereas similar rTMS to the left prefrontal area did not. In addition to providing evidence for the effectiveness of right frontal rTMS for an exaggerated response to trauma-related stimuli, this study provides electrophysiological corroboration of subjective reports of PTSD symptoms.

Subjective report of word-finding and memory deficits in normal aging and dementia.

OBJECTIVE: Compare subjective reports of both memory and word-finding deficits to clinical diagnosis and objective neuropsychological testing. BACKGROUND: With the increasing number of aging individuals with cognitive impairments, effective screening measures would improve the likelihood of detection. Subjective reports of symptoms are typically obtained in clinical settings, yet the validity of these reports is relatively unknown. METHODS: Clinical screening for dementia was carried out at an Alzheimer disease center. Dichotomous ratings for memory and word-finding/language problems were given by patients and neurologists. These ratings were compared with 13 neuropsychological measures of word-finding/language and episodic memory. RESULTS: Ratings of memory by both patients and neurologists correlated well with standard neuropsychological measures of memory. However, both the patients' and physicians' ratings of word-finding/language impairments had notably less of a correlation with the relevant neuropsychological measures of word-finding/language. CONCLUSION: Compared with ratings of memory, similar assessments of word-finding/language difficulties were relatively inaccurate, and thus poor predictors of impairment. It is imperative to develop effective screening methods that will help reveal cognitive impairments, as this issue will almost certainly become more pressing given the projected increase in the number of aging individuals and those with dementia.

Frontal theta and alpha power and coherence changes are modulated by semantic complexity in Go/NoGo tasks.

To study the interactions between semantic processing and motor response inhibition, we recorded scalp EEG as subjects performed a series of Go/NoGo response inhibition tasks whose response criteria depended on different levels of semantic processing. Three different tasks were used. The first required the subject to make a Go/NoGo decision based on pictures of one particular car or one particular dog. The second used pictures of different types of cars and of dogs, and the final task used stimuli that ranged across multiple types of objects and animals. We found that the theta-band EEG power recorded during the NoGo response was attenuated as a function of semantic complexity while the peak latency was delayed in only the most complex category task. Further, frontal alpha-band desynchronization was strongest for the simplest task and remained close to baseline for the other tasks. Finally, there was significant theta-band coherence between the frontal pole and pre-SMA for the NoGo conditions across tasks, which was not found in the Go trials. These findings provide information about how more rostral frontal regions interact with the pre-SMA during response inhibition across different stimuli and task demands: specifically, level of processing affects latency, difficulty affects amplitude, and coherence is affected by whether the decision is Go or NoGo.

Impaired response inhibition in ill Gulf War veterans.

Poor performance on tasks requiring response inhibition has been observed among chronically ill veterans of the 1991 Persian Gulf War. Semantic difficulties have also been reported. We collected event-related potential (ERP) and behavioral data from 25 Gulf War veterans who complained of cognitive difficulties and from 23 matched controls, who were deployed but not symptomatic, while they performed a GO-NOGO task that required both a semantic decision and inhibitory processing. A significantly greater false-alarm rate among the ill veterans was accompanied in the ERP data by significantly reduced amplitude in the NOGO P3, consistent with previous ERP studies of other patient groups that have shown poor inhibitory response performance. This supports the contention that the ill veterans' deficit lies more in inhibiting than in detecting task-related differences in the stimuli.

An fMRI investigation of cognitive stages in reasoning by analogy.

We compared reasoning about four-term analogy problems in the format (A:B::C: D) to semantic and perceptual control conditions that required matching without analogical mapping. We investigated distinct phases of the problem solving process divided into encoding, mapping/inference, and response. Using fMRI, we assessed the brain activation relevant to each of these phases with an emphasis on achieving a better understanding of analogical reasoning relative to these other matching conditions. We predicted that the analogical condition would involve the most cognitive effort in the encoding and mapping/inference phases, while the control conditions were expected to engage greater prefrontal cortex (PFC) activation at the response period. Results showed greater activation for the analogical condition relative to the control conditions at the encoding phase in several predominantly left lateralized and medial areas of the PFC. Similar results were observed for the mapping/inference phase, though this difference was limited to the left PFC and rostral PFC. The response phase resulted in the fastest and most accurate responses in the analogy condition relative to the control conditions. This was accompanied by greater processing within the left lateral and the medial PFC for the control conditions relative to the analogy condition, consistent with most of the cognitive processing of the analogy condition having occurred in the prior task phases. Overall we demonstrate that the left ventral and dorsal lateral, medial, and rostral PFC are important in both the encoding of relational information, mapping and inference processes, and verification of semantic and perceptual responses in four term analogical reasoning.

Estradiol levels during the menstrual cycle differentially affect latencies to right and left hemispheres during dichotic listening: an ERP study.

Many behavioral studies have found high-estrogen phases of the menstrual cycle to be associated with enhanced left-hemisphere processing and low-estrogen phases to be associated with better right-hemisphere processing. This study examined the changing of hemispheric asymmetry during the menstrual cycle by analyzing event-related potential (ERP) data from midline and both hemispheres of 23 women during their performance of a dichotic tasks shown to elicit a left-hemisphere response (semantic categorization) and a right-hemisphere response (complex tones). Each woman was tested during her high-estrogen follicular phase and low-estrogen menstrual phase. Salivary assays of estradiol and progesterone were used to confirm cycle phase. Analyses of the ERP data revealed that latency for each hemisphere was differentially affected by phase and target side, such that latencies to the left hemisphere and from the right ear were shorter during the high-estrogen phase, and latencies to the right hemisphere and from the left ear were shorter during the low-estrogen phase. These findings supply electrophysiological correlates of the cyclically based interhemispheric differences evinced by behavioral studies.

Event-related potentials in semantic memory retrieval.

The involvement of the left temporal lobe in semantics and object naming has been repeatedly demonstrated in the context of language comprehension; however, its role in the mechanisms and time course for the retrieval of an integrated object memory from its constituent features have not been well delineated. In this study, 19 young adults were presented with two features of an object (e.g., "desert" and "humps") and asked to determine whether these two features were congruent to form a retrieval of a specific object ("camel") or incongruent and formed no retrieval while event-related potentials (ERP) were recorded. Beginning around 750 ms the ERP retrieval and nonretrieval waveforms over the left anterior fronto-temporal region show significance differences, indicating distinct processes for retrievals and nonretrievals. In addition to providing further data implicating the left frontal-anterior temporal region in object memory/retrieval, the results provide insight into the time course of semantic processing related to object memory retrieval in this region. The likely semantic process at 750 ms in this task would be coactivation of feature representations common to the same object. The consistency of this finding suggests that the process is stable across individuals. The potential clinical applications are discussed.