Altered Brain Activation in Military Personnel with One or More Traumatic Brain Injuries Following Blast

AbstractExplosive blast is a frequent cause of traumatic brain injury (TBI) among personnel deployed to Afghanistan and Iraq. Functional magnetic resonance imaging (fMRI) with an event-related stimulus-response compatibility task was used to compare 15 subjects with mild, chronic blast-related TBI with 15 subjects who had not experienced a TBI or blast exposure during deployment. Six TBI subjects reported multiple injuries. Relative to the control group, TBI subjects had slightly slower responses during fMRI and increased somatic complaints and symptoms of post-traumatic stress disorder (PTSD) and depression. A between-group analysis indicated greater activation during stimulus-response incompatibility in TBI subjects within the anterior cingulate gyrus, medial frontal cortex, and posterior cerebral areas involved in visual and visual-spatial functions. This activation pattern was more extensive after statistically controlling for reaction time and symptoms of PTSD and depression. There was also a negative relationship between symptoms of PTSD and activation within posterior brain regions. These results provide evidence for increased task-related activation following mild, blast-related TBI and additional changes associated with emotional symptoms. Limitations of this study include no matching for combat exposure and different recruitment strategies so that the control group was largely a community-based sample, while many TBI subjects were seeking services. (JINS, 2012, 18, 89–100)

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Multi-Modal Analysis of Resting-State fMRI Data in mTBI Patients and Association With Neuropsychological Outcomes

Frontiers in Neurology ◽

10.3389/fneur.2021.639760 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jian Shi ◽

Jing Teng ◽

Xianping Du ◽

Na Li

Keyword(s):

Correlation Analysis ◽

Resting State ◽

Brain Injuries ◽

Structural Connectivity ◽

Executive Dysfunction ◽

Brain Regions ◽

Acute Stage ◽

Anterior Cingulate ◽

Control Group ◽

Neuropsychological Outcomes

Various cognitive disorders have been reported for mild traumatic brain injury (mTBI) patients during the acute stage. This acute stage provides an opportunity for clinicians to optimize treatment protocols, which are based on the evaluation of brain structural connectivity. So far, most brain functional magnetic resonance imaging studies are focused on moderate to severe traumatic brain injuries (TBIs). In this study, we prospectively collected resting state data on 50 mTBI within 3 days of injury and 50 healthy volunteers and analyzed them using Amplitude of low-frequency fluctuation (ALFF), Regional Homogeneity (ReHo), graph theory methods and behavior measure, to explore the dysfunctional brain regions in acute mTBI. In our study, a total of 50 patients suffering <3 days mTBI and 50 healthy subjects were tested in rs-fMRI, as well as under neuropsychological examinations including the Wechsler Intelligence Scale and Stroop Color and Word Test. The correlation analysis was conducted between graph theoretic parameters and neuropsychological results. For the mTBI group, the ReHo of the inferior temporal gyrus and the cerebellum superior are significantly lower than in the control group, and the ALFF of the left insula, the cerebellum inferior, and the middle occipital gyrus were significantly higher than in the control group, which implies the dysfunctionality usually observed in Parkinson's disease. Executive function disorder was significantly correlated with the global efficiencies of the dorsolateral superior frontal gyrus and the anterior cingulate cortex, which is consistent with the literature: the acute mTBI patients demonstrate abnormality in terms of motor speed, association, information processing speed, attention, and short-term memory function. Correlation analysis between the neuropsychological outcomes and the network efficiency for the mTBI group indicates that executive dysfunction might be caused by local brain changes. Our data support the idea that the cerebral internal network has compensatory reactions in response to sudden pathological and neurophysiological changes. In the future, multimode rs-fMRI analysis could be a valuable tool for evaluating dysfunctional brain regions after mTBI.

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Cortical activation in alexithymia as a response to emotional stimuli

The British Journal of Psychiatry ◽

10.1192/bjp.bp.106.034728 ◽

2008 ◽

Vol 192 (1) ◽

pp. 32-38 ◽

Cited By ~ 74

Author(s):

Hasse Karlsson ◽

Petri Näätänen ◽

Hanna Stenman

Keyword(s):

Emotion Processing ◽

Three Dimensional ◽

Brain Regions ◽

Physical Symptoms ◽

Cortical Activation ◽

Anterior Cingulate ◽

Control Group ◽

Emotional Stimuli ◽

Healthy Women ◽

The Brain

BackgroundAlexithymia has been shown to be related to many psychiatric and somatic illnesses. Aberrant emotion processing in the brain may underlie several psychiatric disorders. However, little is known about the neurobiological underpinnings of alexithymia.AimsTo determine the way in which the brain processes emotion in alexithymia.MethodThe participants were 10 healthy women with alexithymia and 11 healthy women without this condition, recruited into the study on the basis of their scores on the 20-item Toronto Alexithymia Scale. Four films were projected on a video screen to induce each of three emotional conditions (neutral, amusement, sadness). The brain areas activated during emotional stimuli in the alexithymia group were compared with those activated in the non-alexithymia group. Scans of the distribution of [15O]H2O were acquired using a positron emission tomography (PET) scanner operated in three-dimensional mode.ResultsIn response to emotional stimuli participants with alexithymia activated more parts of their sensory and motor cortices and insula, especially on the left side, and less of their anterior cingulate, compared with the control group.ConclusionsWomen with alexithymia seem to over-activate their ‘bodily’ brain regions, implying a different mode of emotion processing. This may be related to their tendency to experience physical symptoms.

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Altered resting-state functional connectivity of the frontal-striatal circuit in elderly with apathy

PLoS ONE ◽

10.1371/journal.pone.0261334 ◽

2021 ◽

Vol 16 (12) ◽

pp. e0261334

Author(s):

Chizuko Hamada ◽

Toshikazu Kawagoe ◽

Masahiro Takamura ◽

Atsushi Nagai ◽

Shuhei Yamaguchi ◽

...

Keyword(s):

Functional Connectivity ◽

Resting State ◽

Group Analysis ◽

Underlying Mechanism ◽

Brain Regions ◽

Anterior Cingulate ◽

Psychiatric Disease ◽

Resting State Functional Connectivity ◽

Dorsal Anterior Cingulate Cortex ◽

Aged People

Apathy is defined as reduction of goal-directed behaviors and a common nuisance syndrome of neurodegenerative and psychiatric disease. The underlying mechanism of apathy implicates changes of the front-striatal circuit, but its precise alteration is unclear for apathy in healthy aged people. The aim of our study is to investigate how the frontal-striatal circuit is changed in elderly with apathy using resting-state functional MRI. Eighteen subjects with apathy (7 female, 63.7 ± 3.0 years) and eighteen subjects without apathy (10 female, 64.8 ± 3.0 years) who underwent neuropsychological assessment and MRI measurement were recruited. We compared functional connectivity with/within the striatum between the apathy and non-apathy groups. The seed-to-voxel group analysis for functional connectivity between the striatum and other brain regions showed that the connectivity was decreased between the ventral rostral putamen and the right dorsal anterior cingulate cortex/supplementary motor area in the apathy group compared to the non-apathy group while the connectivity was increased between the dorsal caudate and the left sensorimotor area. Moreover, the ROI-to-ROI analysis within the striatum indicated reduction of functional connectivity between the ventral regions and dorsal regions of the striatum in the apathy group. Our findings suggest that the changes in functional connectivity balance among different frontal-striatum circuits contribute to apathy in elderly.

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Correlation between Mild Traumatic Brain Injury-Induced Inflammatory Cytokines and Emotional Symptom Traits: A Systematic Review

Brain Sciences ◽

10.3390/brainsci12010102 ◽

2022 ◽

Vol 12 (1) ◽

pp. 102

Author(s):

Shazia Malik ◽

Omar Alnaji ◽

Mahnoor Malik ◽

Teresa Gambale ◽

Michel Piers Rathbone

Keyword(s):

Systematic Review ◽

Data Analysis ◽

Inflammatory Cytokines ◽

Brain Injuries ◽

Psychological Symptoms ◽

Cochrane Central Register ◽

Post Traumatic Stress ◽

Emotional Symptoms ◽

Similar Clinical Outcome ◽

Emotional Impairments

Both mild traumatic brain injuries (mTBI) and systemic injuries trigger a transient neuroinflammatory response that result in similar clinical outcome. The ensuing physical, cognitive, and emotional symptoms fail to subside in approximately 15–20% of the concussed population. Emotional impairments, particularly depression, anxiety, and post-traumatic stress disorder (PTSD), are commonly associated with poor recovery following mTBI. These emotional impairments also have a significant neuroinflammatory component. We hypothesized that the inflammatory cytokines seen in mTBI patients with emotional symptoms would coincide with those commonly seen in patients with emotional symptoms without mTBI. A systematic review was conducted to identify the most common neuroinflammatory cytokines in the mTBI population with psychological symptoms (depression, anxiety, PTSD). The electronic databases EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED, and PSYCINFO were searched from data inception to 31 August 2021. A systematic screening approach was employed from screening to data analysis. A total of 994 articles were screened, 108 were selected for full article review, and 8 were selected for data analysis. The included studies consisted of 875 patients of which 81.3% were male. The mean sample size of patients with at least one mTBI was 73.8 ± 70.3 (range, 9–213), with a mean age of 33.9 ± 4.8 years. The most common cytokines associated with poor psychological outcomes involving PTSD and/or depression in the chronic mTBI population were IL-6, TNFα, IL-10, and CRP.

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Structural Covariance Networks in Post-Traumatic Stress Disorder: A Multisite ENIGMA-PGC Study

10.1101/2021.03.13.432212 ◽

2021 ◽

Author(s):

Gopalkumar Rakesh ◽

Delin Sun ◽

Mark Logue ◽

Emily Clarke-Rubright ◽

Brian M. O Leary ◽

...

Keyword(s):

Stress Disorder ◽

Occipital Cortex ◽

Brain Regions ◽

Anterior Cingulate ◽

Parahippocampal Gyrus ◽

Centrality Measures ◽

Post Traumatic Stress ◽

Cross Sectional ◽

Structural Covariance ◽

Functional Connections

Introduction - Cortical thickness (CT) and surface area (SA) are established biomarkers of brain pathology in posttraumatic stress disorder (PTSD). Structural covariance networks (SCN) constructed from CT and SA may represent developmental associations, or unique interactions between brain regions, possibly influenced by a common causal antecedent. The ENIGMA-PGC PTSD Working Group aggregated PTSD and control subject data from 29 cohorts in five countries (3439). Methods - Using Destrieux Atlas, we built SCNs and compared centrality measures between PTSD subjects and controls. Centrality is a graph theory measure derived using SCN. Results - Notable nodes with higher CT-based centrality in PTSD compared to controls were left fusiform gyrus, left superior temporal gyrus, and right inferior temporal gyrus. We found sex-based centrality differences in bilateral frontal lobe regions, left anterior cingulate, left superior occipital cortex and right ventromedial prefrontal cortex (vmPFC). Comorbid PTSD and MDD showed higher CT-based centrality in the right anterior cingulate gyrus, right parahippocampal gyrus and lower SA-based centrality in left insular gyrus. Conclusion - Unlike previous studies with smaller sample sizes (less than 318), our study found differences in centrality measures using a sample size of 3439 subjects. This is the first cross-sectional study to examine SCN interactions with age, sex, and comorbid MDD. Although limited to group level inferences, centrality measures offer insights into nodal relationship to the entire functional connectome unlike approaches like seed-based connectivity or independent component analysis. Nodes having higher centrality have greater structural or functional connections, lending them invaluable for translational treatments like neuromodulation.

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Neuroticism and Its Associated Brain Activation in Women With PTSD

Journal of Interpersonal Violence ◽

10.1177/0886260516682519 ◽

2016 ◽

Vol 35 (1-2) ◽

pp. 341-363

Author(s):

Nicholas Brown ◽

Jessica A. Wojtalik ◽

Melissa Turkel ◽

Tessa Vuper ◽

David Strasshofer ◽

...

Keyword(s):

Neural Activity ◽

Interpersonal Violence ◽

Neural Correlates ◽

Brain Regions ◽

Anterior Cingulate ◽

Control Group ◽

Stress Model ◽

Conflict Task ◽

Increased Risk ◽

Diathesis Stress Model

Previous research suggests a diathesis-stress model of posttraumatic stress disorder (PTSD), wherein individuals with high levels of neuroticism who are exposed to traumatic events subsequently develop PTSD. Although studies have established relationships between neuroticism and neurological functioning in various brain regions for healthy and depressed individuals, the specific neural correlates of neuroticism for individuals with PTSD are yet unknown. This relationship is particularly relevant for women, given that their increased risk for PTSD is partially accounted for by their higher baseline levels of neuroticism. The current study examined previously established neural correlates of neuroticism in 61 women (48 women with interpersonal violence [IPV]/PTSD and 13 healthy controls). A specific region of interest map, including the amygdala, hippocampus, parahippocampus, anterior cingulate cortex (ACC), and dorsal medial prefrontal cortex (dmPFC), was examined while participants completed an emotional conflict task. Results showed that the PTSD group had significantly higher neuroticism scores than the healthy control group ( t = 6.90, p < .001). Higher neuroticism scores were associated with increased neural activity in the right dmPFC when participants were instructed to directly attend to faces with negative emotional valences. Significant trends between higher neuroticism scores and greater right amygdala and right ACC activation also emerged for this condition. Finally, neuroticism was found to be associated with right amygdala and right parahippocampal activity when participants were instructed to ignore faces with negative emotional valences. The results of this study lend further evidence to the proposed diathesis-stress model of neuroticism and PTSD. Moreover, findings suggest a significant association between neuroticism and neural activity in brain regions associated with fear and emotion regulation for women with IPV and subsequent PTSD.

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Data-Driven Approach to the Analysis of Real-Time FMRI Neurofeedback Data: Disorder-Specific Brain Synchrony in PTSD

International Journal of Neural Systems ◽

10.1142/s012906572150043x ◽

2021 ◽

pp. 2150043

Author(s):

Jana Zweerings ◽

Kiira Sarasjärvi ◽

Krystyna Anna Mathiak ◽

Jorge Iglesias-Fuster ◽

Fengyu Cong ◽

...

Keyword(s):

Real Time ◽

Brain Activity ◽

Inferior Frontal Gyrus ◽

Self Regulation ◽

Blood Oxygen Level Dependent ◽

Brain Regions ◽

Anterior Cingulate ◽

Data Driven ◽

Post Traumatic Stress ◽

Data Driven Approach

Brain–computer interfaces (BCIs) can be used in real-time fMRI neurofeedback (rtfMRI NF) investigations to provide feedback on brain activity to enable voluntary regulation of the blood-oxygen-level dependent (BOLD) signal from localized brain regions. However, the temporal pattern of successful self-regulation is dynamic and complex. In particular, the general linear model (GLM) assumes fixed temporal model functions and misses other dynamics. We propose a novel data-driven analyses approach for rtfMRI NF using intersubject covariance (ISC) analysis. The potential of ISC was examined in a reanalysis of data from 21 healthy individuals and nine patients with post-traumatic stress-disorder (PTSD) performing up-regulation of the anterior cingulate cortex (ACC). ISC in the PTSD group differed from healthy controls in a network including the right inferior frontal gyrus (IFG). In both cohorts, ISC decreased throughout the experiment indicating the development of individual regulation strategies. ISC analyses are a promising approach to reveal novel information on the mechanisms involved in voluntary self-regulation of brain signals and thus extend the results from GLM-based methods. ISC enables a novel set of research questions that can guide future neurofeedback and neuroimaging investigations.

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The Role of the Lateral Prefrontal Cortex and Anterior Cingulate in Stimulus-Response Association Reversals

Journal of Cognitive Neuroscience ◽

10.1162/jocn.2007.19.1.13 ◽

2007 ◽

Vol 19 (1) ◽

pp. 13-24 ◽

Cited By ~ 21

Author(s):

Benjamin A. Parris ◽

Ngoc J. Thai ◽

Abdelmalek Benattayallah ◽

Ian R. Summers ◽

Timothy L. Hodgson

Keyword(s):

Motor Response ◽

Brain Activity ◽

Brain Regions ◽

Anterior Cingulate ◽

Subcortical Structures ◽

Simple Task ◽

Stimulus Response ◽

Relative Contribution ◽

Behavioral Rules ◽

Subcortical Regions

Many complex tasks require us to flexibly switch between behavioral rules, associations, and strategies. The prefrontal cerebral cortex is thought to be critical to the performance of such behaviors, although the relative contribution of different components of this structure and associated subcortical regions are not fully understood. We used functional magnetic resonance imaging to measure brain activity during a simple task which required repeated reversals of a rule linking a colored cue and a left/right motor response. Each trial comprised three discrete events separated by variable delay periods. A colored cue instructed which response was to be executed, followed by a go signal which told the subject to execute the response and a feedback instruction which indicated whether to “hold” or “flip” the rule linking the colored cue and response. The design allowed us to determine which brain regions were recruited by the specific demands of preparing a rule contingent motor response, executing such a response, evaluating the significance of the feedback, and reconfiguring stimulus-response (SR) associations. The results indicate that an increase in neural activity occurs within the anterior cingulate gyrus under conditions in which SR associations are labile. In contrast, lateral frontal regions are activated by unlikely/unexpected perceptual events regardless of their significance for behavior. A network of subcortical structures, including the mediodorsal nucleus of the thalamus and striatum were the only regions showing activity that was exclusively correlated with the neurocognitive demands of reversing SR associations. We conclude that lateral frontal regions act to evaluate the behavioral significance of perceptual events, whereas medial frontal-thalamic circuits are involved in monitoring and reconfiguring SR associations when necessary.

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The brain function state in different phase and relation with clinical symptoms in migraine: an fMRI study based on Reho

10.21203/rs.3.rs-198584/v1 ◽

2021 ◽

Author(s):

Ming Lei ◽

Jun-Jian Zhang ◽

Dong-Mei Wu

Keyword(s):

Clinical Symptoms ◽

Depression Scale ◽

Brain Regions ◽

Regional Homogeneity ◽

Anterior Cingulate ◽

Control Group ◽

Hamilton Depression Scale ◽

Montreal Neurological Institute ◽

Lingual Gyrus ◽

The Brain

Abstract Objective Through regional homogeneity (ReHo) to analyze the activation of brain regions at different phase in migraineurs and to explore its relationship with clinical symptoms. Methods we analyzed resting-state Resting brain functional magnetic resonance in 19 patients with episodes and 22 patients with interictal phase,22 healthy controls. Using regional homogeneity (ReHo) method to do post-processing. All subjects were evaluated by Montreal cognitive assessment scale (MoCA), simple mental state examination (MMSE), Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD). Subjects' clinical indicators (such as frequency of attack, course of disease, duration of each headache, and severity of headache) were correlated with ReHo values of brain regions. This study was approved by the ethics committee of Yangtze river shipping general hospital. Results the episodes group compared with the interictal group, Montreal Neurological Institute (MNI) (-9,42༌15)༌is that the ReHo value of bilateral anterior cingulate cortex was lower active than the interictal group; and Montreal Neurological Institute (MN) (-3༌-24༌66) ,the ReHo value of bilateral paracentrallobule was stronger active than the interictal group(P < 0.01). Compared with the control group, patients in interictal phase had lower activation in bilateral cuneus and bilateral lingual gyrus, MNI of the two are (9, -84, 36) and (0,-72,6). No significant different brain area was found between the episodes group and the control group. In episodes group, significant correlation was found between attack frequency and ReHo value of the bilateral paracentrallobule (r = 0.492; p = 0.038). Conclusion We need to observe the course of migraine as a whole. Even in the interictal, it may affect the development of the disease through the cuneus and lingual gyrus. ACC regulates different states of migraine by inducing anti-injury sensation regulation function. Paracentric lobule is not only associated with migraine attacks, but also with the frequency. it may have an effect with the outcome of subsequent migraines, whether become chronic, and the remodeling of the brain.

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Detecting Abnormal Neuronal Activity in a Chronic Migraine Model by Egr1-EGFP Transgenic Mice

Frontiers in Neuroscience ◽

10.3389/fnins.2021.705938 ◽

2021 ◽

Vol 15 ◽

Author(s):

Fei Wang ◽

Weiqing Jiang ◽

Li Gao ◽

Chen Liu ◽

Mingzhu Deng ◽

...

Keyword(s):

Transgenic Mice ◽

Chronic Migraine ◽

Fluorescent Protein ◽

Brain Regions ◽

Anterior Cingulate ◽

Temporal Association ◽

Emotional Symptoms ◽

Early Growth Response Gene ◽

Green Fluorescent ◽

Based Medicine

Chronic migraine (CM) is a highly disabling neurological disorder characterized by recurrent headache accompanied by a variety of sensory and/or emotional symptoms. However, the mechanisms of migraine onset and its chronicity have not been elucidated. The present study was designed to search for brain regions and neurons that were abnormally activated by CM and might be related to its pathogenesis and different concomitant symptoms. CM models were established here by repeated intraperitoneal injection of nitroglycerin (NTG) every other day for 9 days to early growth response gene 1 (Egr1)-enhanced green fluorescent protein (EGFP) transgenic mice, which allowed monitoring of neuronal activities in the whole brain. CM-related behaviors were recorded through head grooming test and light aversion assay. Elevation of Egr1 expression signals was detected in trigeminal nucleus caudalis (TNC), primary somatosensory cortex (SSp), lateral amygdala nucleus (LA), primary visual area (VISp), and temporal association areas (TEa) 2 h after the last injection of NTG by immunofluorescence and digital slice scanning technology. Meanwhile, no change of Egr1 expression was found in auditory areas (AUD), CA1, ectorhinal area (ECT), piriform (PIR), and anterior cingulate area (ACC). Furthermore, with the strongest support by evidence-based medicine among the current limited oral treatments of CM, topiramate was administrated every day for 11 days from 2 days before the first NTG injection. The results showed that topiramate partially improved the photophobia behavior of CM models in the short-term with gradually weakened efficacy as the course of the disease prolonged. Meanwhile, NTG-induced increase in Egr1 expression was completely reversed in TNC, SSp, and VISp and partially reduced in LA and TEa by topiramate at the same time point mentioned above. In conclusion, the current results suggested that the abnormal hyperactivities in TNC, SSp and VISp were associated with the pathogenesis of CM.

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