Selectively reduced regional cortical volumes in post-traumatic stress disorder.
TL;DR: Cortical parcellation of magnetic resonance imaging data was performed to test for volumetric differences in pregenual ACC and SC, and results are consistent with contemporary schemes regarding functional and structural dissection of frontal cortex, and suggest specific regional cortical pathology in PTSD.
Abstract: Different subterritories of anterior cingulate cortex (ACC) and adjacent ventromedial frontal cortex have been shown to serve distinct functions. This scheme has influenced contemporary pathophysiologic models of psychiatric disorders. Prevailing neurocircuitry models of post-traumatic stress disorder (PTSD) implicate dysfunction within pregenual ACC and subcallosal cortex (SC), as well as amygdala and hippocampus. In the current study, cortical parcellation of magnetic resonance imaging data was performed to test for volumetric differences in pregenual ACC and SC, between women with PTSD and trauma-exposed women without PTSD. The PTSD group exhibited selectively decreased pregenual ACC and SC volumes. These results are consistent with contemporary schemes regarding functional and structural dissection of frontal cortex, and suggest specific regional cortical pathology in PTSD.
Citations
More filters
TL;DR: Additional research will be needed to clarify the exact role of each component of the fear circuitry in the anxiety disorders, determine whether functional abnormalities identified in the Anxiety disorders represent acquired signs of the disorders or vulnerability factors that increase the risk of developing them, and use functional neuroimaging to predict treatment response and assess treatment-related changes in brain function.
1,617 citations
Cites background from "Selectively reduced regional cortic..."
...The findings of several studies suggest diminished volumes or gray matter densities in the ACC in PTSD (Corbo et al, 2005; Kasai et al, 2008; Rauch et al, 2003; Woodward et al, 2006; Yamasue et al, 2003), and smaller ACC volumes have been associated with greater PTSD symptom severity (Woodward et…...
[...]
TL;DR: It is proposed that posttraumatic stress disorder is characterized by exaggerated amygdala responses and deficient frontal cortical function and deficiencies in extinction and the capacity to suppress attention/response to trauma-related stimuli, as well as deficient hippocampal function.
1,247 citations
Cites background or methods from "Selectively reduced regional cortic..."
...Given that rACC, SC, and medial orbitofrontal cortex are ypothesized to be candidate human homologues of rodent nfralimbic cortex (Ongur and Price 2000), these findings conerge with the observation of decreased rACC and SC volumes in TSD (Rauch et al 2003)....
[...]
...An initial cortical parcellation study (Rauch et al 2003) was ecently performed and found that Vietnam combat-exposed urses with PTSD versus without PTSD exhibited selectively educed volumes in rACC and SC....
[...]
...Moreover, we have proposed that this regional athophysiology in PTSD corresponds to exuberant acquisition f conditioned fear and exaggerated fear responses, as well as eficient extinction recall and an incapacity to appreciate safe ontexts....
[...]
TL;DR: Neuroimaging research reveals heightened amygdala responsivity in PTSD during symptomatic states and during the processing of trauma‐unrelated affective information and suggests diminished volumes, neuronal integrity, and functional integrity of the hippocampus in PTSD.
Abstract: The last decade of neuroimaging research has yielded important information concerning the structure, neurochemistry, and function of the amygdala, medial prefrontal cortex, and hippocampus in posttraumatic stress disorder (PTSD). Neuroimaging research reviewed in this article reveals heightened amygdala responsivity in PTSD during symptomatic states and during the processing of trauma-unrelated affective information. Importantly, amygdala responsivity is positively associated with symptom severity in PTSD. In contrast, medial prefrontal cortex appears to be volumetrically smaller and is hyporesponsive during symptomatic states and the performance of emotional cognitive tasks in PTSD. Medial prefrontal cortex responsivity is inversely associated with PTSD symptom severity. Lastly, the reviewed research suggests diminished volumes, neuronal integrity, and functional integrity of the hippocampus in PTSD. Remaining research questions and related future directions are presented.
1,058 citations
TL;DR: These results provide evidence for exaggerated amygdala responsivity, diminished medial prefrontal cortexresponsivity, and a reciprocal relationship between these 2 regions during passive viewing of overtly presented affective stimuli unrelated to trauma in PTSD.
Abstract: Background: Previous functional neuroimaging studies have demonstrated exaggerated amygdala responses and diminished medial prefrontal cortex responses during the symptomatic state in posttraumatic stress disorder (PTSD). Objectives: To determine whether these abnormalities also occur in response to overtly presented affective stimuli unrelated to trauma; to examine the functional relationship between the amygdala and medial prefrontal cortex and their relationship to PTSD symptom severity in response to these stimuli; and to determine whether responsivity of these regions habituates normally across repeated stimulus presentations in PTSD.
908 citations
TL;DR: This study provides the first direct evidence that dendritic remodeling in the prefrontal cortex may underlie the functional deficits in attentional control that are symptomatic of stress-related mental illnesses.
Abstract: Stressful life events have been implicated clinically in the pathogenesis of mental illness, but the neural substrates that may account for this observation remain poorly understood. Attentional impairments symptomatic of these psychiatric conditions are associated with structural and functional abnormalities in a network of prefrontal cortical structures. Here, we examine whether chronic stress-induced dendritic alterations in the medial prefrontal cortex (mPFC) and orbital frontal cortex (OFC) underlie impairments in the behaviors that they subserve. After 21 d of repeated restraint stress, rats were tested on a perceptual attentional set-shifting task, which yields dissociable measures of reversal learning and attentional set-shifting, functions that are mediated by the OFC and mPFC, respectively. Intracellular iontophoretic injections of Lucifer yellow were performed in a subset of these rats to examine dendritic morphology in layer II/III pyramidal cells of the mPFC and lateral OFC. Chronic stress induced a selective impairment in attentional set-shifting and a corresponding retraction (20%) of apical dendritic arbors in the mPFC. In stressed rats, but not in controls, decreased dendritic arborization in the mPFC predicted impaired attentional set-shifting performance. In contrast, stress was not found to adversely affect reversal learning or dendritic morphology in the lateral OFC. Instead, apical dendritic arborization in the OFC was increased by 43%. This study provides the first direct evidence that dendritic remodeling in the prefrontal cortex may underlie the functional deficits in attentional control that are symptomatic of stress-related mental illnesses.
870 citations
Cites background from "Selectively reduced regional cortic..."
...Attentional impairments symptomatic of these conditions are associated with structural and functional anomalies in a circuit of prefrontal cortical structures (Cohen and Servan-Schreiber, 1992; Drevets et al., 1997; Casey et al., 2002; Rauch et al., 2003)....
[...]
References
More filters
[...]
01 Jan 1996
TL;DR: In The Emotional Brain, Joseph LeDoux investigates the origins of human emotions and explains that many exist as part of complex neural systems that evolved to enable us to survive.
Abstract: Apa yang terjadi di otak kita untuk membuat kita merasa takut, benci, marah, dan sukacita? Apakah kita mengendalikan emosi kita, atau apakah emosi itu mengendalikan kita? Apakah hewan memiliki emosi? Bagaimana pengalaman traumatis pada masa anak-anak awal dalam mempengaruhi perilaku pada masa dewasa, walaupun kita tidak memiliki memori sadar terhadap pemngalaman itu? Dalam The Emotional Brain, Joseph LeDoux menyelidiki asal-usul emosi manusia dan menjelaskan kompleksitas evolusi sistem syaraf yang memungkinkan kita dapa bertahan hidup.
Joseph LeDoux adalah salah satu profil peniliti utama dalam emotional Intelligence karya Danierl Goleman yang merupakan penulis terkemuka di bidang neurosains. Di dalam buku The Emotional Brain yan provokatif ini, ia mengeksplorasi mekanisme otak yang mendasari emosi kita mekanisme yang baru sekarang terungkap.
3,849 citations
"Selectively reduced regional cortic..." refers background in this paper
...Contemporary neurobiological models of PTSD have been substantially influenced by animal data regarding the anatomy of fear conditioning [5], together with findings from initial neuroimaging studies of people with PTSD (see [4] for review)....
[...]
TL;DR: The research evidence indicates that the CAPS has excellent reliability, yielding consistent scores across items, raters, and testing occasions, and there is also strong evidence of validity: the CAPs has excellent convergent and discriminant validity, diagnostic utility, and sensitivity to clinical change.
Abstract: The Clinician-Administered PTSD Scale (CAPS) is a structured interview for assessing posttraumatic stress disorder (PTSD) diagnostic status and symptom severity. In the 10 years since it was developed, the CAPS has become a standard criterion measure in the field of traumatic stress and has now been used in more than 200 studies. In this paper, we first trace the history of the CAPS and provide an update on recent developments. Then we review the empirical literature, summarizing and evaluating the findings regarding the psychometric properties of the CAPS. The research evidence indicates that the CAPS has excellent reliability, yielding consistent scores across items, raters, and testing occasions. There is also strong evidence of validity: The CAPS has excellent convergent and discriminant validity, diagnostic utility, and sensitivity to clinical change. Finally, we address several concerns about the CAPS and offer recommendations for optimizing the CAPS for various clinical research applications.
1,812 citations
TL;DR: It is suggested that consolidation of extinction learning potentiates infralimbic activity, which inhibits fear during subsequent encounters with fear stimuli, indicating that medial prefrontal cortex might store long-term extinction memory.
Abstract: Conditioned fear responses to a tone previously paired with a shock diminish if the tone is repeatedly presented without the shock, a process known as extinction. Since Pavlov it has been hypothesized that extinction does not erase conditioning, but forms a new memory. Destruction of the ventral medial prefrontal cortex, which consists of infralimbic and prelimbic cortices, blocks recall of fear extinction, indicating that medial prefrontal cortex might store long-term extinction memory. Here we show that infralimbic neurons recorded during fear conditioning and extinction fire to the tone only when rats are recalling extinction on the following day. Rats that froze the least showed the greatest increase in infralimbic tone responses. We also show that conditioned tones paired with brief electrical stimulation of infralimbic cortex elicit low freezing in rats that had not been extinguished. Thus, stimulation resembling extinction-induced infralimbic tone responses is able to simulate extinction memory. We suggest that consolidation of extinction learning potentiates infralimbic activity, which inhibits fear during subsequent encounters with fear stimuli.
1,694 citations
TL;DR: In monozygotic twins discordant for trauma exposure, it is found evidence that smaller hippocampi indeed constitute a risk factor for the development of stress-related psychopathology.
Abstract: In animals, exposure to severe stress can damage the hippocampus. Recent human studies show smaller hippocampal volume in individuals with the stress-related psychiatric condition posttraumatic stress disorder (PTSD). Does this represent the neurotoxic effect of trauma, or is smaller hippocampal volume a pre-existing condition that renders the brain more vulnerable to the development of pathological stress responses? In monozygotic twins discordant for trauma exposure, we found evidence that smaller hippocampi indeed constitute a risk factor for the development of stress-related psychopathology. Disorder severity in PTSD patients who were exposed to trauma was negatively correlated with the hippocampal volume of both the patients and the patients’ trauma-unexposed identical co-twin. Furthermore, severe PTSD twin pairs—both the trauma-exposed and unexposed members—had significantly smaller hippocampi than non-PTSD pairs.
1,469 citations
TL;DR: There is a fundamental dichotomy between the functions of anterior and posterior cingulate cortices, which subserves primarily executive functions related to the emotional control of visceral, skeletal, and endocrine outflow and evaluation of spatial orientation and memory.
Abstract: The cingulate gyrus is a major part of the "anatomical limbic system" and, according to classic accounts, is involved in emotion. This view is oversimplified in light of recent clinical and experimental findings that cingulate cortex participates not only in emotion but also in sensory, motor, and cognitive processes. Anterior cingulate cortex, consisting of areas 25 and 24, has been implicated in visceromotor, skeletomotor, and endocrine outflow. These processes include responses to painful stimuli, maternal behavior, vocalization, and attention to action. Since all of these activities have an affective component, it is likely that connections with the amygdala are critical for them. In contrast, posterior cingulate cortex, consisting of areas 29, 30, 23, and 31, contains neurons that monitor eye movements and respond to sensory stimuli. Ablation studies suggest that this region is involved in spatial orientation and memory. It is likely that connections between posterior cingulate and parahippocampal cortices contribute to these processes. We conclude that there is a fundamental dichotomy between the functions of anterior and posterior cingulate cortices. The anterior cortex subserves primarily executive functions related to the emotional control of visceral, skeletal, and endocrine outflow. The posterior cortex subserves evaluative functions such as monitoring sensory events and the organism's own behavior in the service of spatial orientation and memory.
1,334 citations