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ABSTRACT: We examined the relationship between a remote history of concussions with current symptoms of depression in retired professional athletes. Thirty retired National Football League (NFL) athletes with a history of concussion and 29 age- and IQ-matched controls without a history of concussion were recruited. We found a significant correlation between the number of lifetime concussions and depressive symptom severity using the Beck Depression Inventory II. Upon investigating a three-factor model of depressive symptoms (affective, cognitive, and somatic; Buckley et al., 2001) from the BDI-II, the cognitive factor was the only factor that was significantly related to concussions. In general, NFL players endorsed more symptoms of depression on all three Buckley factors compared with matched controls. Findings suggest that the number of self-reported concussions may be related to later depressive symptomology (particularly cognitive symptoms of depression).
Archives of Clinical Neuropsychology 05/2013; · 2.18 Impact Factor
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Continuum (Minneapolis, Minn.). 04/2013; 19(2 Dementia):480-8.
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ABSTRACT: OBJECTIVES To assess cognitive impairment and depression in aging former professional football (National Football League [NFL]) players and to identify neuroimaging correlates of these dysfunctions. DESIGN We compared former NFL players with cognitive impairment and depression, cognitively normal retired players who were not depressed, and matched healthy control subjects. SETTING Research center in the North Texas region of the United States. PATIENTS Cross-sectional sample of former NFL players with and without a history of concussion recruited from the North Texas region and age-, education-, and IQ-matched controls. Thirty-four retired NFL players (mean age, 61.8 years) underwent neurological and neuropsychological assessment. A subset of 26 players also underwent detailed neuroimaging; imaging data in this subset were compared with imaging data acquired in 26 healthy matched controls. MAIN OUTCOME MEASURES Neuropsychological measures, clinical diagnoses of depression, neuroimaging mea-sures of white matter pathology, and a measure of cerebral blood flow. RESULTS Of the 34 former NFL players, 20 were cognitively normal. Four were diagnosed as having a fixed cognitive deficit; 8, mild cognitive impairment; 2, dementia; and 8, depression. Of the subgroup in whom neuroimaging data were acquired, cognitively impaired participants showed the greatest deficits on tests of naming, word finding, and visual/verbal episodic memory. We found significant differences in white matter abnormalities in cognitively impaired and depressed retired players compared with their respective controls. Regional blood flow differences in the cognitively impaired group (left temporal pole, inferior parietal lobule, and superior temporal gyrus) corresponded to regions associated with impaired neurocognitive performance (problems with memory, naming, and word finding). CONCLUSIONS Cognitive deficits and depression appear to be more common in aging former NFL players compared with healthy controls. These deficits are correlated with white matter abnormalities and changes in regional cerebral blood flow.
JAMA neurology. 01/2013;
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ABSTRACT: We propose that pre-supplementary motor area (pre-SMA)-thalamic interactions govern processes fundamental to semantic retrieval of an integrated object memory. At the onset of semantic retrieval, pre-SMA initiates electrical interactions between multiple cortical regions associated with semantic memory subsystems encodings as indexed by an increase in theta-band EEG power. This starts between 100-150ms after stimulus presentation and is sustained throughout the task. We posit that this activity represents initiation of the object memory search, which continues in searching for an object memory. When the correct memory is retrieved, there is a high beta-band EEG power increase, which reflects communication between pre-SMA and thalamus, designates the end of the search process and resultant in object retrieval from multiple semantic memory subsystems. This high beta signal is also detected in cortical regions. This circuit is modulated by the caudate nuclei to facilitate correct and suppress incorrect target memories.
Brain and Language 09/2012; · 3.12 Impact Factor
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ABSTRACT: 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.
NeuroToxicology 06/2012; 33(5):1096-105. · 3.10 Impact Factor
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ABSTRACT: Major depression in adolescents is a significant public health concern because of its frequency and severity. To examine the neurobiological basis of depression in this population, the authors studied functional activation characteristics of the brain before and after antidepressant treatment in antidepressant-naive depressed adolescents and healthy comparison subjects.
Depressed (N=19) and healthy (N=21) adolescents, ages 11 to 18 years, underwent functional MRI assessment while viewing fearful and neutral facial expressions at baseline and again 8 weeks later. The depressed adolescents received 8 weeks of open-label fluoxetine treatment after their baseline scan.
Voxel-wise whole brain analyses showed that depressed youths have exaggerated brain activation compared with healthy comparison subjects in multiple regions, including the frontal, temporal, and limbic cortices. The 8 weeks of fluoxetine treatment normalized most of these regions of hyperactivity in the depressed group. Region-of-interest analyses of the areas involved in emotion processing indicated that before treatment, depressed youths had significantly greater activations to fearful relative to neutral facial expressions than did healthy comparison subjects in the amygdala, orbitofrontal cortex, and subgenual anterior cingulate cortex bilaterally. Fluoxetine treatment decreased activations in all three regions, as compared with the repeat scans of healthy comparison subjects.
While effective treatments are available, the impact of depression and its treatment on the brain in adolescents is understudied. This study confirms increases in brain activation in untreated depressed adolescents and demonstrates reductions in these aberrant activations with treatment.
American Journal of Psychiatry 01/2012; 169(4):381-8. · 12.54 Impact Factor
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ABSTRACT: Linear statistical models are used very effectively to assess task-related differences in EEG power spectral analyses. Mixed models, in particular, accommodate more than one variance component in a multisubject study, where many trials of each condition of interest are measured on each subject. Generally, intra- and intersubject variances are both important to determine correct standard errors for inference on functions of model parameters, but it is often assumed that intersubject variance is the most important consideration in a group study. In this article, we show that, under common assumptions, estimates of some functions of model parameters, including estimates of task-related differences, are properly tested relative to the intrasubject variance component only. A substantial gain in statistical power can arise from the proper separation of variance components when there is more than one source of variability. We first develop this result analytically, then show how it benefits a multiway factoring of spectral, spatial, and temporal components from EEG data acquired in a group of healthy subjects performing a well-studied response inhibition task. Hum Brain Mapp, 2011. © 2011 Wiley-Liss, Inc.
Human Brain Mapping 11/2011; · 5.88 Impact Factor
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Xiufeng Li,
Jeffrey S Spence,
David M Buhner, John Hart,
C Munro Cullum,
Melanie M Biggs,
Andrea L Hester,
Timothy N Odegard,
Patrick S Carmack,
Richard W Briggs,
Robert W Haley
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ABSTRACT: PURPOSE: To determine, with arterial spin labeling (ASL) perfusion magnetic resonance (MR) imaging and physostigmine challenge, if abnormal hippocampal blood flow in ill Gulf War veterans persists 11 years after initial testing with single photon emission computed tomography and nearly 20 years after the 1991 Gulf War. Materials and Methods: The local institutional review board approved this HIPAA-compliant study. Veterans were screened for contraindications and gave written informed consent before the study. In a semiblinded retrospective protocol, veterans in three Gulf War illness groups-syndrome 1 (impaired cognition), syndrome 2 (confusion-ataxia), and syndrome 3 (central neuropathic pain)-and a control group received intravenous infusions of saline in an initial session and physostigmine in a second session, 48 hours later. Each infusion was followed by measurement of hippocampal regional cerebral blood flow (rCBF) with pulsed ASL. A mixed-effects linear model adjusted for age was used to test for differences in rCBF after the cholinergic challenge across the four groups. Results: Physostigmine significantly decreased hippocampal rCBF in control subjects (P < .0005) and veterans with syndrome 1 (P < .05) but significantly increased hippocampal rCBF in veterans with syndrome 2 (P < .005) and veterans with syndrome 3 (P < .002). The abnormal increase in rCBF was found to have progressed to the left hippocampus of the veterans with syndrome 2 and to both hippocampi of the veterans with syndrome 3. Conclusion: Chronic hippocampal perfusion dysfunction persists or worsens in veterans with certain Gulf War syndromes. ASL MR imaging examination of hippocampal rCBF in a cholinergic challenge experiment may be useful as a diagnostic test for this condition.
Radiology 09/2011; 261(1):218-25. · 5.73 Impact Factor
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ABSTRACT: 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.
The Journal of neuropsychiatry and clinical neurosciences 01/2011; 23(1):40-7. · 2.34 Impact Factor
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ABSTRACT: A better understanding of carbon dioxide (CO(2)) effect on brain activity may have a profound impact on clinical studies using CO(2) manipulation to assess cerebrovascular reserve and on the use of hypercapnia as a means to calibrate functional magnetic resonance imaging (fMRI) signal. This study investigates how an increase in blood CO(2), via inhalation of 5% CO(2), may alter brain activity in humans. Dynamic measurement of brain metabolism revealed that mild hypercapnia resulted in a suppression of cerebral metabolic rate of oxygen (CMRO(2)) by 13.4% ± 2.3% (N=14) and, furthermore, the CMRO(2) change was proportional to the subject's end-tidal CO(2) (Et-CO(2)) change. When using functional connectivity MRI (fcMRI) to assess the changes in resting-state neural activity, it was found that hypercapnia resulted in a reduction in all fcMRI indices assessed including cluster volume, cross-correlation coefficient, and amplitude of the fcMRI signal in the default-mode network (DMN). The extent of the reduction was more pronounced than similar indices obtained in visual-evoked fMRI, suggesting a selective suppression effect on resting-state neural activity. Scalp electroencephalogram (EEG) studies comparing hypercapnia with normocapnia conditions showed a relative increase in low frequency power in the EEG spectra, suggesting that the brain is entering a low arousal state on CO(2) inhalation.
Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 01/2011; 31(1):58-67. · 5.46 Impact Factor
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ABSTRACT: We used functional magnetic resonance imaging (fMRI) to study semantic memory processing in 38 Gulf War veterans in 3 affected groups (Syndromes 1, 2, and 3) and normal-deployed controls. Subjects were given the Semantic Object Retrieval Test (SORT), which requires participants to decide whether two features combine and result in the retrieval of a specific object (e.g., "desert" and "humps" → "camel"). Differences between groups were calculated using a repeated measures analysis of variance (ANOVA). Then, regions of interest were constructed and correlations assessed between the percent signal change (PSC) within these regions, followed by correlations between behavioral measures and PSC. We found affected groups performed less well on the SORT than the controls did, and behavioral differences were correlated to PSC within the caudate and thalamus. The combination of performance deficits and functional neuroimaging differences between affected Gulf War veterans and deployed normal controls begins to establish a neurobiological basis for their word-finding deficits.
Brain Imaging and Behavior 12/2010; 4(3-4):248-55. · 1.66 Impact Factor
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ABSTRACT: 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.
International journal of psychophysiology: official journal of the International Organization of Psychophysiology 12/2010; 78(3):215-24. · 3.05 Impact Factor
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ABSTRACT: 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.
Journal of the neurological sciences 10/2010; 297(1-2):1-5. · 2.32 Impact Factor
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ABSTRACT: Cognitive impairment is a key factor that threatens functionality and quality of life in seniors. Given the projection that the population of individuals 65 years of age and older will double within the next 25 years, a critical need exists to identify and test effectiveness of protocols that target higher-order cognitive skills such as gist reasoning to maximize cognitive capacity in later life.
This study examined the effects of eight hours of gist reasoning training in 26 cognitively normal seniors between the ages of 64-85 years (M = 74.23, SD = 6.67).
Findings suggest that top-down strategy-based gist reasoning training significantly improved abstraction ability, a skill relevant to everyday life, as well as generalized to untrained measures of executive function including concept abstraction, cognitive switching, and verbal fluency. Individuals with lower baseline ability to abstract gist showed the greatest gain in the target domain trained.
These findings highlight the potential value of engaging in cognitively challenging activities that involve gist reasoning, to strengthen and preserve cognitive capacity with aging.
International Journal of Geriatric Psychiatry 10/2010; 26(9):961-8. · 2.42 Impact Factor
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ABSTRACT: Compare subjective reports of both memory and word-finding deficits to clinical diagnosis and objective neuropsychological testing.
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.
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.
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.
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.
Cognitive and behavioral neurology: official journal of the Society for Behavioral and Cognitive Neurology 09/2010; 23(3):185-91. · 1.09 Impact Factor
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ABSTRACT: To explore the temporal sequence of, and the relationship between, the left and right hemispheres (LH and RH) during semantic memory (SM) processing we identified the neural networks involved in the performance of functional MRI semantic object retrieval task (SORT) using group independent component analysis (ICA) in 47 healthy individuals. SORT requires participants to determine whether word pairs describing object features combine to retrieve an object. Functional network connectivity (FNC) was used to assess the correlations between components' time courses. Results showed that semantic left and right hemisphere networks comprise two independent ICA components. The components' time courses were highly correlated and RH activation preceded that of the LH. Moreover, this correlation was significantly stronger in better vs. poorer performers of the SORT. These results indicate an early activation of the RH that is closely followed by activation of the LH, to facilitate performance during word retrieval from SM.
Brain and Cognition 04/2009; 70(2):238-46. · 3.17 Impact Factor
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ABSTRACT: Posttraumatic stress disorder (PTSD) is one of the few psychiatric conditions in which a subjective decrease in emotional range serves as a diagnostic criterion. In order to investigate whether veterans with chronic PTSD also experienced objective limitations in emotional perception, the authors administered the Aprosodia Battery to a group of 11 veterans with chronic PTSD, nine subjects with right hemisphere damage, seven subjects with left hemisphere damage, and 12 comparison subjects. The patients with PTSD displayed significant deficiencies in the comprehension and discriminative components of affective speech, similar in severity and performance profile on the Aprosodia Battery to the individuals with focal right hemisphere damage due to ischemic infarction.
The Journal of neuropsychiatry and clinical neurosciences 02/2009; 21(1):52-8. · 2.34 Impact Factor
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ABSTRACT: 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.
Journal of the International Neuropsychological Society 10/2008; 14(5):815-22. · 2.76 Impact Factor
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ABSTRACT: A new method is developed for analyzing the time-varying spectral content of EEG data collected in cognitive tasks. The goal is to extract and summarize the most salient features of numerical results, which span space, time, frequency, task conditions, and multiple subjects. Direct generalization of an established approach for analyzing event-related potentials, which uses sequential PCA followed by ANOVA to test for differences between conditions across subjects, gave unacceptable results. The new method, termed STAT-PCA, advocates statistical testing for differences between conditions within single subjects, followed by sequential PCA across subjects. In contrast to PCA-ANOVA, it is demonstrated that STAT-PCA gives results which: 1) isolate task-related spectral changes, 2) are insensitive to the precise definition of baseline power, 3) are stable under deletion of a random subject, and 4) are interpretable in terms of the group-averaged power. Furthermore, STAT-PCA permits the detection of activity that is not only different between conditions, but also common to both conditions, providing a complete yet parsimonious view of the data. It is concluded that STAT-PCA is well suited for analyzing the time-varying spectral content of EEG during cognitive tasks.
NeuroImage 10/2008; 45(1):109-21. · 5.89 Impact Factor
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ABSTRACT: The authors aim to delineate cognitive dysfunction associated with posttraumatic stress disorder (PTSD) by evaluating a well-defined cohort of former World War II prisoners of war (POWs) with documented trauma and minimal comorbidities. The authors studied a cross-sectional assessment of neuropsychological performance in former POWs with PTSD, PTSD with other psychiatric comorbidities, and those with no PTSD or psychiatric diagnoses. Participants who developed PTSD had average IQ, while those who did not develop PTSD after similar traumatic experiences had higher IQs than average (approximately 116). Those with PTSD performed significantly less well in tests of selective frontal lobe functions and psychomotor speed. In addition, PTSD patients with co-occurring psychiatric conditions experienced impairment in recognition memory for faces. Higher IQ appears to protect individuals who undergo a traumatic experience from developing long-term PTSD, while cognitive dysfunctions appear to develop with or subsequent to PTSD. These distinctions were supported by the negative and positive correlations of these cognitive dysfunctions with quantitative markers of trauma, respectively. There is a suggestion that some cognitive decrements occur in PTSD patients only when they have comorbid psychiatric diagnoses.
The Journal of neuropsychiatry and clinical neurosciences 02/2008; 20(3):309-16. · 2.34 Impact Factor
