Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder

Fear conditioning is an established model for investigating posttraumatic stress disorder (PTSD). However, symptom triggers may vaguely resemble the initial traumatic event, differing on a variety of sensory and affective dimensions. We extended the fear-conditioning model to assess generalization of conditioned fear on fear processing neurocircuitry in PTSD. Military veterans (n=67) consisting of PTSD (n=32) and trauma-exposed comparison (n=35) groups underwent functional magnetic resonance imaging during fear conditioning to a low fear-expressing face while a neutral face was explicitly unreinforced. Stimuli that varied along a neutral-to-fearful continuum were presented before conditioning to assess baseline responses, and after conditioning to assess experience-dependent changes in neural activity. Compared with trauma-exposed controls, PTSD patients exhibited greater post-study memory distortion of the fear-conditioned stimulus toward the stimulus expressing the highest fear intensity. PTSD patients exhibited biased neural activation toward high-intensity stimuli in fusiform gyrus (P<0.02), insula (P<0.001), primary visual cortex (P<0.05), locus coeruleus (P<0.04), thalamus (P<0.01), and at the trend level in inferior frontal gyrus (P=0.07). All regions except fusiform were moderated by childhood trauma. Amygdala–calcarine (P=0.01) and amygdala–thalamus (P=0.06) functional connectivity selectively increased in PTSD patients for high-intensity stimuli after conditioning. In contrast, amygdala–ventromedial prefrontal cortex (P=0.04) connectivity selectively increased in trauma-exposed controls compared with PTSD patients for low-intensity stimuli after conditioning, representing safety learning. In summary, fear generalization in PTSD is biased toward stimuli with higher emotional intensity than the original conditioned-fear stimulus. Functional brain differences provide a putative neurobiological model for fear generalization whereby PTSD symptoms are triggered by threat cues that merely resemble the index trauma.     

Wound healing effect of methanolic leaf extract of Napoleona vogelii(Family:Lecythidaceae) in rats

Objective:To investigate the wound healing properly of Napoleona vogelii leaf extract in folkloric medicine.Methods:Roth sexes of adult albino rats(n=25) were used in this study and another group(n=30) were subjected to acute toxicity test(LD_(50)) of the plant extract.For the LD_(50),three randomized groups of 5 rats were first treated with 10,100,1 000 mg/kg body weight(bw),orally.This w as followed by a second treatment of 1500,3000,and 5 000 mg/kg bw of the leaf extract with continual monitoring of the animals for mortality or non-mortality.Incision wounds(1.3cm) were created on the skin of five groups of 5 rals using surgical blade under anesthesia.The first group was topically treated with petroleum jelly alone,group 2 was topically applied 400 mg/mL w/v of the reference drug,Neobaein,while group 3-5 were topically treated with 5-50 mg/mL w/v of the plant extract,respectively.Results:The percentage yield of the extract was 49.80%w/w dry matter.The phytochemical analysis revealed several bioactive constituents including glycosides,tannins,alkaloids,perpenoids.saponins,steroids,proteins,and carbohydrates.The LD_(50) was beyond our experimental limit and was not determined.Increased concentrations(5,20,and 50mg/mL w/v) of the extract had significant(ANOVA,P0.05) healing effect on the incision wounds giving rise to 125%-140% while treatmentawith Neobacin resulted in 150% healing effect on the third treatment regimen compared to the control(100%).Conclusions:These data indicate that Napoleona vogelii leaf extract contains potent bioactive compounds containing wound healing activity,substantiating its use as a wound healer in folkloric medicine.     

Effects of chronic mild traumatic brain injury on white matter integrity in Iraq and Afghanistan war veterans

Mild traumatic brain injury (TBI) is a common source of morbidity from the wars in Iraq and Afghanistan. With no overt lesions on structural MRI, diagnosis of chronic mild TBI in military veterans relies on obtaining an accurate history and assessment of behavioral symptoms that are also associated with frequent comorbid disorders, particularly posttraumatic stress disorder (PTSD) and depression. Military veterans from Iraq and Afghanistan with mild TBI (n = 30) with comorbid PTSD and depression and non‐TBI participants from primary (n = 42) and confirmatory (n = 28) control groups were assessed with high angular resolution diffusion imaging (HARDI). White matter‐specific registration followed by whole‐brain voxelwise analysis of crossing fibers provided separate partial volume fractions reflecting the integrity of primary fibers and secondary (crossing) fibers. Loss of white matter integrity in primary fibers (P < 0.05; corrected) was associated with chronic mild TBI in a widely distributed pattern of major fiber bundles and smaller peripheral tracts including the corpus callosum (genu, body, and splenium), forceps minor, forceps major, superior and posterior corona radiata, internal capsule, superior longitudinal fasciculus, and others. Distributed loss of white matter integrity correlated with duration of loss of consciousness and most notably with “feeling dazed or confused,” but not diagnosis of PTSD or depressive symptoms. This widespread spatial extent of white matter damage has typically been reported in moderate to severe TBI. The diffuse loss of white matter integrity appears consistent with systemic mechanisms of damage shared by blast‐ and impact‐related mild TBI that involves a cascade of inflammatory and neurochemical events. Hum Brain Mapp 34:2986–2999, 2013. © 2012 Wiley Periodicals, Inc.     

FreeSurfer-based segmentation of hippocampal subfields: A review of methods and applications,with a novel quality control procedure for ENIGMA studies and other collaborative efforts

Structural hippocampal abnormalities are common in many neurological and psychiatric disorders, and variation in hippocampal measures is related to cognitive performance and other complex phenotypes such as stress sensitivity. Hippocampal subregions are increasingly studied, as automated algorithms have become available for mapping and volume quantification. In the context of the Enhancing Neuro Imaging Genetics through Meta Analysis Consortium, several Disease Working Groups are using the FreeSurfer software to analyze hippocampal subregion (subfield) volumes in patients with neurological and psychiatric conditions along with data from matched controls. In this overview, we explain the algorithm's principles, summarize measurement reliability studies, and demonstrate two additional aspects (subfield autocorrelation and volume/reliability correlation) with illustrative data. We then explain the rationale for a standardized hippocampal subfield segmentation quality control (QC) procedure for improved pipeline harmonization. To guide researchers to make optimal use of the algorithm, we discuss how global size and age effects can be modeled, how QC steps can be incorporated and how subfields may be aggregated into composite volumes. This discussion is based on a synopsis of 162 published neuroimaging studies (01/2013–12/2019) that applied the FreeSurfer hippocampal subfield segmentation in a broad range of domains including cognition and healthy aging, brain development and neurodegeneration, affective disorders, psychosis, stress regulation, neurotoxicity, epilepsy, inflammatory disease, childhood adversity and posttraumatic stress disorder, and candidate and whole genome (epi-)genetics. Finally, we highlight points where FreeSurfer-based hippocampal subfield studies may be optimized.     

Treatment efficacy of social communication skills training after traumatic brain injury: a randomized treatment and deferred treatment controlled trial

Dahlberg CA, Cusick CP, Hawley LA, Newman JK, Morey CE. Harrison-Felix CL, Whiteneck GG. Treatment efficacy of social communication skills training after traumatic brain injury: a randomized treatment and deferred treatment controlled trial.

Objective

To evaluate the efficacy of a replicable group treatment program to improve social communication skills after traumatic brain injury (TBI).

Design

Randomized treatment and deferred treatment controlled trial, with follow-up at 3, 6, and 9 months post-treatment.

Setting

Community.

Participants

Volunteer sample of 52 people with TBI who were at least 1 year postinjury, who received rehabilitation, and who had identified social communication deficits.

Intervention

Twelve weekly group sessions (1.5h each) to improve social communication.

Main Outcome Measures

The Profile of Functional Impairment in Communication (PFIC), Social Communication Skills Questionnaire–Adapted (SCSQ-A), Goal Attainment Scale (GAS), Craig Handicap Assessment and Reporting Technique–Short Form social integration and occupation subscales, Community Integration Questionnaire social integration and productivity subscales, and Satisfaction With Life Scale (SWLS).

Results

Independent samples t test analysis showed significant treatment effect compared with no treatment on 7 of 10 of the PFIC subscales (P range, .024 to <.001) and the SCSQ-A (P=.005) after the first 12 weeks of the study. After 12 weeks of treatment for all participants, repeated-measures analysis showed significant improvements from baseline on 9 of 10 PFIC subscales (P range, .01−.001), SCSQ-A (P≤.001), GAS (P≤.001), and SWLS (P=.011). At 6-month follow-up, scores were significantly better than baseline on 6 of 10 PFIC scales (P range, .01−.001), the SCSQ-A (P≤.001), GAS (P≤.001), and SWLS (P≤.001).

Conclusions

TBI subjects who received social communication skills training had improved communication skills that were maintained on follow-up. Overall life satisfaction for participants was improved.     

Two-year trends in physical performance following supervised exercise among community-dwelling older veterans

The extent to which exercise can delay the normal decline in physical performance associated with aging is unknown. We examined the impact of 2 years of supervised exercise on cardiovascular fitness, flexibility, and strength in a group of elderly (age 65-74) veterans. Seventy-five patients exercised 3 days/week for 90-minute sessions emphasizing aerobic, flexibility, and strength development. Thirty-six (47%) completed 2 years of a voluntary supervised exercise program (n = 16-25 with complete data). Over a 2-year follow-up period, cardiovascular outcome variables improved significantly: metabolic equivalents increased 20% (7.4 +/- 2.2 to 9.0 +/- 2.4, P less than 0.001) and submaximal heart rate decreased 7% (131.4 +/- 14.8 to 121.0 +/- 18.5 beats/minute, P = 0.06). Resting heart rate decreased 8% (68.5 +/- 8.0 to 63.6 +/- 8.4 beats/minute, P = 0.02) but this difference did not reach statistical significance. Flexibility, measured by hamstring length, improved 11% (57.5 +/- 15.1 to 64.0 +/- 11.1 degrees, P = 0.02). Strength variables did not improve. The study indicates that improvements in cardiovascular function and flexibility achieved by the elderly in the early stages of an exercise program can be maintained for at least 2 years.     

Oxidative metabolism of the human eosinophil

We have compared the oxidative metabolism of human eosinophils (80%-90% purity) to that of neutrophils. Hexose monophosphate (HMP) shunt activity of eosinophils was higher than that of neutrophils under either resting or phagocytizing conditions. Eosinophil HMP shunt activity also was stimulated by phorbol myristate acetate, a membrane- active agent. Eosinophils showed a marked incorporation of 125I into trichloroacetic acid-insoluble material under resting conditions, which increased markedly during phagocytosis. Eosinophils likewise showed a greater reduction of nitroblue tetrazolium dye during phagocytosis than did neutrophils. Measurement of other parameters of oxidative metabolism indicated that eosinophils generated superoxide anion following phagocytosis and also elicited a burst of chemiluminescence similar to that observed during phagocytosis by neutrophils. Measurement of NADPH oxidase activity demonstrated that this enzyme was 3-6 times more active in fractions isolated from eosinophils than in corresponding fractions isolated from neutrophils; this was observed over a range of substrate concentrations. The eosinophil enzyme sedimented differently than the neutrophil enzyme with differential centrifugation; neither showed sedimentation characteristics of peroxidase. These data indicate that eosinophils possess a similar, although in some ways more potent, oxidative burst than neutrophils and are consistent with a role for NADPH oxidase in the initiation of that burst.