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Nov 29, 2012 - Victor G. Carrion & Shane S. Wong & Hilit Kletter. Published ...... 1351–1356. Jackowski, A. P., Douglas-Palumberi, H., Jackowski, M., Win, L.,.
J Fam Viol (2013) 28:53–61 DOI 10.1007/s10896-012-9489-2

IPVAND CHILDREN’S ADJUSTMENT: THE ROLE OF EMOTION REGULATION AND NEUROFUNCTIONAL CAPACITIES

Update on Neuroimaging and Cognitive Functioning in Maltreatment-Related Pediatric PTSD: Treatment Implications Victor G. Carrion & Shane S. Wong & Hilit Kletter

Published online: 29 November 2012 # Springer Science+Business Media New York 2012

Abstract This article reviews maltreatment-related pediatric posttraumatic stress disorder (PTSD) neuroimaging and neuropsychology research. Existent interventions that target brain networks associated with PTSD and cognitive impairment are highlighted. Furthermore, the benefits of combining neuroimaging and neuropsychology research in treatment outcomes are discussed. To conduct this review, a literature search was done utilizing the words MRI, structural, functional, neuropsychological testing, children, maltreatment, treatment, and PTSD. This was supplemented with a direct search of developmental trauma experts. Results from the neuroimaging studies found differences in the total cerebral volume, prefrontal cortex, hippocampus, cerebellum, superior temporal gyrus, corpus callosum, and other regions in maltreatment-related childhood PTSD. Neuropsychological findings demonstrate deficits in memory, attention, learning, and executive function that correspond to these brain regions. Existent and novel psychotherapeutic interventions address these deficits. These interventions may be directed at key networks associated with cognitive processing. Future directions include the implementation of treatment outcome research integrating psychotherapy with putative biological and psychological markers.

V. G. Carrion (*) Division of Child and Adolescent Psychiatry and Child Development, Stanford University, Stanford, CA 94305-5719, USA e-mail: [email protected] V. G. Carrion : S. S. Wong : H. Kletter Stanford Early Life Stress Research Program, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA

Keywords Pediatric PTSD . Child maltreatment . Magnetic resonance imaging . Neuropsychological testing . Interventions

Annually, an estimated 6 million children in the United States are referred to Child Protective Services for alleged maltreatment, with approximately 702,000 children determined to be victims of abuse or neglect in 2009 (U.S. Department of Health and Human Services 2010). Maltreatment of children can significantly impact their social, emotional, and cognitive development. Children with a history of maltreatment are at increased risk for cognitive deficits and consequent poor academic performance. At school, children exposed to traumatic stress are more likely to be absent (Hurt et al. 2001), have low reading ability and achievement (Perez and Widom 1994), and poor academic performance (Schwab-Stone et al. 1995). The development of posttraumatic stress disorder (PTSD) may be a potential mechanism by which maltreatment leads to functional impairment in critical areas of cognitive development. For example, De Bellis (2001) has argued that increased catecholamines, neurotransmitters such as dopamine and norepinephrine that are released during times of stress, are associated with a prolonged hyperarousal state that can impede development during maturation, which in turn compromises cognitive functioning. Although not all maltreated children develop psychopathology after a history of maltreatment, a significant proportion experience negative sequelae such as posttraumatic symptoms. PTSD is characterized by three different clusters of symptoms: (a) re-experiencing, such as nightmares and flashbacks; (b) avoidance and numbing, such as inability to recall an aspect of the traumatic memory or restricted affect; and (c) hyperarousal, such as insomnia or poor concentration (American Psychiatric Association 2000).

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During the past 15 years, advancements in the developmental psychophysiology of PTSD have shed light onto the anatomical underpinnings associated with the cognitive impairments that may result from a history of maltreatment. The advent of magnetic resonance imaging (MRI) has facilitated this investigation. This methodology has been welcomed by developmental neuroscientists because of its excellent spatial resolution and pediatric tolerability due to its lack of requirements for radiation or contrast. Parallel to this work, the field of neuropsychology continues to clarify the cognitive deficits of youth who have experienced developmental trauma and stress. Discovering neural networks and cognitive deficits associated with PTSD may lead to the identification of disease markers, which can further inform the development of novel interventions and predict treatment outcome. Studies of adult patients with PTSD have shown abnormalities in brain imaging and cognitive functioning, but the literature on pediatric populations is more limited. Over the past 15 years, however, studies using increasingly advanced neuroimaging techniques have identified putative brain networks associated with cognitive deficits in pediatric PTSD. The aims of the present review are to examine brain imaging studies involving children with maltreatment-related PTSD, to examine how these relate to neuropsychological findings, and to highlight how addressing these cognitive limitations is a characteristic of effective treatments. We discuss implications of treatment outcome research combining both neuroimaging and cognitive functioning.

Method A literature search utilizing the keywords MRI, structural, functional, neuropsychological testing, children, maltreatment, treatment, and PTSD was conducted as well as a direct search of developmental trauma experts in the area of maltreatment-related PTSD research. Relevant neuroimaging studies and neurocognitive examinations of children with PTSD secondary to maltreatment were identified through multiple searches. A total of 14 cognitive psychology and 17 neuroimaging articles were reviewed.

Results Total Cerebral Volume Reduced brain volumes have been observed in pediatric PTSD. Three early studies (Carrion et al. 2001; De Bellis et al. 1999, 2002a) of children with PTSD found reduced intracranial and cerebral volumes. Most recently, a comparison of 30 children with PTSD and a history of interpersonal

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trauma, and 15 healthy controls (age and gender matched), found that children with PTSD showed reduced regions of the prefrontal cortex (Carrion et al. 2010a). Lower brain volume may represent a risk factor for pediatric PTSD by compromising the cognitive resources required to adaptively process a traumatic event. The Prefrontal Cortex (PFC) and Executive Function The PFC is an anterior frontal lobe structure extensively interconnected with other cortical and subcortical regions consistent with its major role in attention shifting and fear conditioning. In healthy individuals, the PFC supports cognitive control, the ability to filter and suppress information and actions in favor of shifting attention to relevant information and responses (Casey et al. 2002). Human studies by Owen and colleagues (1991) have shown that individuals with PFC lesions have deficits in shifting attention. On cognitive testing, children with maltreatment-related PTSD perform worse on measures of attention, abstract reasoning, and executive function higher level cognitive processes such as planning, problem-solving, inhibition, and mental flexibility (Beers and De Bellis 2002). De Bellis and colleagues (2009) more recently found that the severity of symptoms correlated with poorer performance on multiple cognitive domains including language, reading, visual-spatial, attention, and executive function. Beyond trauma exposure, Schoeman et al. (2009) found that the presence of PTSD in children was associated with attention, visual memory, and nonverbal concept formation deficits. Saltzman and colleagues (2006) showed that low IQ, which may reflect impairments in multiple cognitive domains, was associated most specifically with the re-experiencing symptoms of PTSD. Most recently, Samuelson et al. (2010) found that children with PTSD exhibited slower and less effective learning, greater sensitivity to interference, and impaired effect of rehearsal on memory acquisition. Consistent with these cognitive impairments, Saigh et al. (1997) found that adolescents with PTSD had lower scores on an academic achievement test. These robust findings of impairment in attention, learning, and executive function implicate the dysfunction of the PFC in pediatric PTSD. Network connections between the medial PFC (mPFC) and the amygdala are involved in the management of stress, emotion, and impulses. Individuals with bilateral damage to this region have deficits in emotion regulation, including changes in the physiological stress response (Anderson et al. 2006). Neuroimaging studies have suggested that the mPFC exerts inhibitory control over autonomic output such as heart rate, respiration, and digestion, as well as endocrine functions such as metabolism, growth and development, and mood (Wang et al. 2005). Consequently, damage to this region results in disinhibition of psychological and

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physiological responses to stress. Animal studies conducted by Morgan and colleagues (1993) have shown that when the mPFC is damaged, unlearning of a conditioned response known as extinction does not occur normally, resulting in a marked increase in fear reactivity. Consistent with these animal studies, Heberlein et al. (2008) showed that patients with mPFC damage have difficulty interpreting social and emotional cues, and human imaging studies have shown that the PFC is preferentially active during the extinction of fear (Gottfried and Dolan 2004), supporting the argument that impairments in the PFC are associated with PTSD. An early neuroimaging study found no difference in the PFC between maltreated children and healthy subjects (De Bellis et al. 1999). However, Carrion et al. (2001) later found that maltreated children showed attenuation of frontal lobe asymmetry due to greater left frontal gray matter in comparison to healthy controls, suggesting impaired frontal lobe functioning. In a follow-up study, De Bellis et al. (2002b) found reduced white matter volume in the PFC among children with a history of maltreatment. Recently, Carrion et al. (2010b) investigated the relationship of the stress hormone cortisol to PFC volume among children with a history of interpersonal trauma. Children with PTSD showed decreased left ventral and left inferior prefrontal gray volumes. Furthermore, high prebedtime cortisol levels were associated with reduced left ventral PFC gray volume. These findings suggest a potential link between cortisol dysregulation and PFC volume. Within the PFC, differences specific to the mPFC have also been found in neuroimaging studies of maltreated children. De Bellis and colleagues (2000) used single voxel proton magnetic resonance spectroscopy (proton MRS) to measure the relative concentration of N-acetylaspartate and creatine, a marker of neural integrity, in the anterior cingulate. The ratio of N-acetylaspartate to creatine was lower in the maltreated subjects with PTSD, suggesting abnormal neuronal metabolism. In a later study, Richert et al. (2006) found increased gray matter volume in areas of the medial PFC among 23 children with PTSD symptoms, further suggesting aberrant development of these regions. Most recently, a functional imaging (fMRI) study using a “Go/ No-Go” task that presents youth with continuous stimuli that they either have to respond to (Go) or ignore (No Go) to assess sustained attention and response inhibition found that adolescents with maltreatment-related PTSD showed relatively decreased activation of the middle frontal cortex and increased activation in the left medial frontal gyrus and anterior cingulate gyrus (Carrion et al. 2008). These findings suggest that children with maltreatment-related PTSD are not utilizing key areas of the PFC to the same extent as the healthy age and gender-matched control counterparts. Impaired structure and function of the PFC may confer specific stress vulnerabilities associated with the pathophysiology of PTSD and cognitive impairments in children.

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The Hippocampus and Memory The hippocampus is a medial temporal brain structure in the limbic system that plays an essential role in new learning and memory. In healthy individuals, the hippocampus is engaged during encoding and retrieval of memory, especially episodic memories, which involve ongoing life experiences (Tulving and Markowitsch 1998). However, individuals with PTSD seem to have difficulties regulating memories. This leads to intrusive thoughts and symptoms of reexperiencing, or conversely, memories may become absent, leading to inability to recall important details or selective amnesia. According to a meta-analysis by Johnsen and Asbjørnsen (2008), the literature robustly demonstrates that adults with PTSD have impairments in verbal memory performance. In children, Moradi and colleagues (1999) demonstrated an association between PTSD and deficits in everyday memory performance, such as remembering names and faces. A second study replicated the findings of poor overall memory performance while also demonstrating a bias in favor of recalling negative information (Moradi et al. 2000). More recently, two other studies by Saigh et al. (2006) and Yasik et al. (2007) showed that children with trauma-related PTSD evidenced lower scores on general and verbal memory tasks along with learning deficits. Even when controlling for exposure to trauma, the presence of PTSD is associated with both impaired visual and verbal memory (De Bellis et al. 2010; Samuelson et al. 2010). These cognitive manifestations suggest common involvement of the hippocampus in the pathophysiology of PTSD. Animal research has shown that one potential mechanism of damage to the hippocampus is through corticosterone, the animal analogue to cortisol in humans, which Sapolsky et al. (1990) found to be neurotoxic, or destroying neural cells, if secreted in high levels. In human studies of patients with Cushing’s disease, which is characterized by excessive release of cortisol over long periods of time, hippocampal volume reductions in brain imaging have been demonstrated and correlated to deficits in verbal declarative memory (Starkman et al. 1992). Reductions in hippocampal volume have been consistently found in adults with PTSD (Smith 2005), including adults with a childhood history of abuse (Bremner et al. 1997). Clinical studies of adults with PTSD have also demonstrated increased sensitivity of the negative feedback system of the hypothalamic-pituitary-adrenal (HPA) axis, which is responsible for cortisol secretion (Yehuda et al. 1993). These studies suggest that the stress resulting from trauma may lead to dysregulation of cortisol levels. Periods of high cortisol levels can be neurotoxic to regions such as the hippocampus that are rich in glucocorticoid receptors to which cortisol binds. Gilbertson and colleagues (2002), however, found that a smaller hippocampus

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can be a risk factor for PTSD by studying twin siblings of veterans who were not exposed to trauma. This last study does not rule out the potential neurotoxic effects of stress in this structure, but suggests the possibility of a smaller hippocampal volume as an added risk factor. Studying PTSD as it unfolds during development will help elucidate this dilemma. Cross-sectional data has been unable to replicate adult findings of a smaller hippocampus among children (Woon and Hedges 2008). However, elevated salivary cortisol has been found in maltreated children with PTSD (Carrion et al. 2002), and greater sensitivity to negative feedback in cortisol suppression has been demonstrated in traumatized adolescents (Goenjian et al. 1996). Given the insidious nature in which cortisol may render its developmental effects, longitudinal designs are paramount. In addition to six cross-sectional studies, two longitudinal studies have investigated the hippocampus in maltreatmentrelated PTSD in children. Although the results are inconclusive, the recent studies suggest developmental differences that were not observed in cross-sectional studies. De Bellis et al. (1999) found no differences in the hippocampal volumes of 44 children with maltreatment-related PTSD compared to controls. These results were replicated in another independent sample of 28 PTSD subjects (De Bellis et al. 2002a). In the first longitudinal study, De Bellis et al. (2001) again found no differences in the hippocampus volume at baseline, follow-up, or across time in nine prepubertal children with PTSD. However, a secondary data analysis on the pooled sample from the two previous cross-sectional studies found larger segmental white-matter volume in the hippocampus when compared to control subjects (Tupler and De Bellis 2006). Carrion and colleagues (2001) conducted an MRI study comparing 24 children with PTSD to 24 control subjects matched for age and gender. They found that the total hippocampal volume of the PTSD group was on average 8.5 % smaller than in control participants, but this difference was not significant after controlling for total brain volume. However, a meta-analysis by Woon and Hedges (2008) of the four earlier structural MRI studies found that hippocampal volume did not differ from that of healthy controls. In a more recent longitudinal study of a sample of 15 children with a history of maltreatment, Carrion and colleagues (2007) reported changes in hippocampal volume over an ensuing 12 to 18-month interval. The severity of PTSD and cortisol levels independently predicted a reduction in hippocampal volume when controlling for pubertal maturation and gender. Utilizing fMRI and a memory task, Carrion et al. (2010b) compared 16 children with PTSD secondary to a history of interpersonal trauma to 11 healthy controls. The results showed that the clinical sample demonstrated reduced activation of the right hippocampus during memory retrieval. Within the PTSD group, the severity

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of avoidance and emotional numbing symptoms correlated with reduced left hippocampal activation during retrieval. These results suggest that memory deficits in children with PTSD may be related to activation deficits in the hippocampus. The discrepancy between the consistent findings of reduced hippocampal volume found among adults with a childhood history of maltreatment and the inconsistent findings among maltreated child populations may be secondary to developmental processes. Maltreatment-induced overexposure to cortisol may damage the hippocampal structure, but these effects may not emerge until later development. Therefore, reduced hippocampal volume may result only after years of PTSD or chronic stress. In support of this hypothesis, a study of rats exposed to early stress and sacrificed at different ages showed that differences in the hippocampus only emerge after young adulthood (Andersen and Teicher 2004). The unexposed rats showed a marked rise in synaptic density that was not observed in rats exposed to early stress. The Cerebellum and Attention The cerebellum is also a key structure involved in emotion processing and fear conditioning via its connection with limbic structures and the HPA axis (Schutter and Van Honk 2005). The importance of the cerebellar vermis in emotion regulation has been demonstrated by patients with isolated cerebellar vermal disease, who are commonly found to have personality changes involving flattening of affect (Schmahmann and Sherman 1998). As part of the emotional numbing cluster of PTSD, symptoms of affective flattening implicate the involvement of the cerebellum. The cerebellum has also been shown to be involved in attention (Schmahmann et al. 2007). Indeed, studies by De Bellis and colleagues (2009) of children with maltreatmentrelated PTSD have demonstrated deficits in attention, a finding replicated by Schoeman and colleagues (2009). More specifically, Beers and De Bellis (2002) found greater impulsivity, distractibility, and errors on tasks of sustained attention. Given the evidence of attention impairments among children, the cerebellum likely plays a role in the pathophysiology of childhood PTSD. Studies of maltreatment-related PTSD in children have also found differences in the cerebellum. In a study of 58 maltreated children, De Bellis and Kuchibhatla (2006) found that the left, right, and total cerebellar volume was smaller in the PTSD group, a difference that persisted after adjusting volumes for cerebral volume, sociodemographic, and IQ variables. In this study, there was a positive correlation between cerebellar volume and age of onset of the traumatic event associated with PTSD. In addition, Carrion and colleagues (2009) analyzed a PTSD group with a

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history of maltreatment and found smaller gray matter volume in the pons and in the posterior vermis area. The cerebellar findings may underlie the emotional numbing and attention impairments of PTSD. Furthermore, given the dorsal pons central role in the noradrenergic pathway that affects arousal via the locus coeruleus (Bremner et al. 1996), the reduced area findings may be related to an exaggerated stress response. Other Regions and Cognitive Deficits Other regions of interest have been identified in neuroimaging studies of children with maltreatment-related PTSD. De Bellis and colleagues (1999) and De Bellis et al. (2002a) reported decreased midbody and posterior corpus callosum (CC) areas. Carrion and colleagues (2009) similarly found corpus callosum reduction in the PTSD group; however, the mean reduction of 8.7 % did not reach statistical significance when covaried for intracranial area. De Bellis and Keshavan (2003) showed that children with chronic PTSD did not show the normal age-related increases in the corpus callosum, resulting in smaller posterior CC volumes. A study by Jackowski and colleagues (2008) using diffusion tensor imaging found an integrity reduction in the medial and posterior areas of CC in children with PTSD. The corpus callosum (CC) controls communication between the left and right hemispheres of the brain (inter-hemispheric) of multiple processes, including emotion and stressrelated arousal. Specifically, the medial and posterior areas of the CC contain interhemispheric projections from brain structures that mediate the processing of emotional stimuli and memory – core processes that are disturbed in PTSD. Thomas and De Bellis (2004) found larger pituitary volumes among maltreated children with chronic PTSD, but only among pubertal/post-pubertal adolescents. In addition, larger pituitary volumes were associated with a history of suicidal ideation among PTSD subjects. The pituitary gland secretes ACTH, which stimulates the adrenal glands to release cortisol, reinforcing the concept of dysregulation of the biological stress response. Finally, De Bellis et al. (2002b) found structural abnormalities of the superior temporal gyrus (STG) in an MRI study comparing 43 maltreated children diagnosed with PTSD with 61 nonmaltreated healthy subjects. Right, left, and total STG volumes were larger in the PTSD group than in healthy children. The STG has also been implicated as a critical structure in social cognition, with connections to the temporolimbic areas including the hippocampus and neocortical areas in the PFC. Treatment Implications Neuropsychological research and advancements in the field of MRI imaging have allowed us to identify specific brain

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regions and cognitive functions associated with exposure to trauma during development. Abnormalities in crucial brain regions are associated with deficits in cognitive abilities such as attention, memory, learning, and executive function. Treatment interventions for traumatized children have focused on improving cognitive, emotional, and social development. Currently, the first line of intervention for children with PTSD is psychotherapy; hence, in this review we focus on this type of intervention. The most widely known and researched psychotherapy for youth with PTSD symptoms is trauma focused cognitive-behavioral therapy (TF-CBT), which exposes children to their trauma narrative and helps identify trauma-related triggers in order to: (a) overcome avoidance of traumatic memories, (b) teach affect modulation and coping strategies, (c) change maladaptive cognitions, and (d) allow processing of the story (Cohen and Mannarino 2008; Smith et al. 2007). The telling of the narrative helps to organize fragmented sensory and emotional memories and integrate them into an autobiographical memory. TF-CBT has been shown to reduce hyperarousal and avoidance symptoms in children exposed to intimate partner violence by helping them distinguish between real and generalized fears, learning relaxation techniques, and facilitating direct talk with the caregiver about the domestic violence experience (Cohen et al. 2011). Additionally, TF-CBT teaches behavioral management by teaching caregivers effective parenting skills that allows them to manage the emotional and behavioral dysregulation that accompanies their child’s trauma (Cohen et al. 2010). March and colleagues (1998) designed the multi-modal trauma treatment protocol (MMTT) as a group intervention for children exposed to single-incident trauma. MMTT utilizes developmentally sensitive methods such as storybooks, narrative exposure, cognitive games, and peer modeling to promote habituation to conditioned fear, revision of maladaptive trauma-induced cognitive schemas, and coping with disturbing affect and physiological sensations. MMTT has been delivered effectively in both school and community mental health settings (Amaya-Jackson et al. 2003). Cognitive-behavioral intervention for trauma in schools (CBITS) is a 10-session group intervention incorporating relaxation training, combating of negative thoughts, social problem-solving, and exposure to stress through imagination, writing, or drawing. This intervention has been shown to improve psychosocial function in children exposed to violence (Stein et al. 2003). The Stanford cue-centered therapy (CCT) combines CBT techniques with insight-oriented and other techniques. It is a manual-based individual treatment with a primary focus on teaching families to identify trauma-related reminders (cues). It is designed for youth who face ongoing stressors, such as inner city youth who are chronically exposed to domestic and community violence. CCT teaches the

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association of cues to current behaviors, emotions, thoughts, and physiological reactions (Carrion and Hull 2010). The child and caregiver are educated on the development of fear networks. The child engages in gradual exposure to cues while replacing maladaptive responses with more adaptive ones. Other components of CCT include coping strategies and telling of the trauma narrative aimed at enabling the child to identify and appropriately express emotions, correct distorted cognitions, fill in memory gaps, and integrate traumatic events into the greater context of his/her life. Furthermore, CCT fosters collaboration between the caregiver, child, and therapist with emphasis on the caregiver as a coach to enhance the caregiver/child relationship and increase sense of efficacy and empowerment of the youth through knowledge. Non-CBT based treatments that have shown promise include eye movement desensitization and reprocessing (EMDR) and child-parent therapies. EMDR teaches the individual to identify feelings and cognitions in specific situations and to differentiate between positive and negative correlates (Ahmad and Sundelin-Wahlsten 2008). The person is trained to identify a “safe place” to focus on while following the therapist’s finger movements. Still following the finger movements, the person is then asked to recall the most terrifying memory while exploring associated emotions and thoughts. This is repeated until the individual no longer experiences distress. EMDR has been proven successful in reducing trauma-related memories and their associated symptoms in children exposed to natural disaster (Chemtob et al. 2002). Child-parent psychotherapy (CPP) posits that young children rely on their parents as the primary attachment figures for safety and that trauma destroys the child’s perception of the parent as a capable and reliable protector (Lieberman et al. 2005). CPP involves parent-child sessions in which the therapist supports the dyad in using play, words, and other forms of expression order to convey and respond to emotional needs, co-create a narrative that breaks the silence about the trauma, regulate traumatic stress, and restore trust in the relationship. Parent-child interaction therapy (PCIT) has also been found to improve social functioning, emotional regulation, and behavioral problems through play therapy and live coaching aimed at enhancing parent-child attachment (Thomas and Zimmer-Gembeck 2011). The therapist observes the parent and child through a one-way mirror and provides immediate feedback through an earpiece to the parent to improve behavioral management of the child. Furthermore, Copping and colleagues (2001) developed the intergenerational trauma treatment model (ITTM), which has shown improvement in social functioning in traumatized children. ITTM combines dysfunctional thought records with diagrams to monitor ‘pathways,’ fluctuations, and regressions within the child/caregiver

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relationship, with the belief that changes in family relationships result in generalization to other relationships for the child. The Behavior Choice Program is then introduced to caregivers to learn to modify their own behaviors and allow their child to develop self-responsibility and impulse control.

Discussion Neuroimaging and cognitive psychology research have facilitated the identification of risk factors and markers associated with maltreatment-related pediatric PTSD. Volumetric and functional abnormalities of key brain regions may reflect cognitive deficits associated with PTSD, implicating differences in brain response and/or compensatory patterns of activity. Findings from such research match target areas from current effective treatment interventions in pediatric PTSD. The field will benefit from the integration of neuroimaging, cognitive psychology, and treatment trials. Treatment outcome research combining these areas of study will assist in gaining empirical validity of novel and existent treatments. Further, markers of treatment response may help direct specific interventions such as cognitive rehabilitative strategies for specific individuals. For example, the reduction of symptoms by strengthening a child’s ability to focus, may also improve learning and academic performance. Therapies designed to improve specific symptoms and cognitive deficits may also improve the brain function of associated regions of interest. The abnormal neuroimaging findings in the mPFC structure and function, for example, may confer risk for developing PTSD following maltreatment, given the PFC’s role in regulating physiological responses, extinguishing fear conditioning, and interpreting emotional cues. Damage to the PFC may therefore impair the appreciation of the stressful nature of a situation, leading to inappropriate psychological and physiological reactivity to social stress. Therefore, behavioral improvements from treatments that facilitate extinction of a fearful response and strengthen executive functioning may be reflected in parallel improvements in PFC functions, such as enhancing prefrontal inhibition of amygdala fear conditioned processes. As presented above, existing therapeutic modalities for pediatric PTSD target improvements in cognitive function, as well as emotional processing and social functioning. These functions involve multiple neural circuits that include the PFC, hippocampus, and cerebellum. Research integrating treatment trials with neuroimaging will help demarcate with specificity how different interventions engage each of these regions. Other fields in anxiety research have already pursued the integration of treatment outcome with neuroimaging and neuropsychological testing. For example, a

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number of adult imaging studies have demonstrated the potential use of neuroimaging in predicting treatment response to cognitive-behavioral therapy (Schienle et al. 2009). However, such research has been limited due to the cost, amount of time, and the extensive training required to become proficient in imaging techniques. Thus, further studies are needed to develop more efficient methods for combining neuroimaging with treatment interventions. In addition, cognitive functioning correlates may help guide treatment development and selection. In order to design appropriate treatment outcome trials that integrate neuroimaging, developmentally sensitive neurofunctional tasks will need to address current impairments in children with PTSD. For example, tasks need to be developed that will help assess a child’s ability to sustain attention and improve memory and learning. These are fundamental cognitive processes that not only support everyday academic and social functioning, but also support treatment objectives to reduce PTSD, such as modulation of a fearful response, re-evaluation of a negative perception or control of a hypervigilant state. Pediatric PTSD research will benefit from the design and implementation of treatment outcome research that integrates neuroimaging techniques and cognitive testing. The “on and off” nature of the symptoms of PTSD in children, secondary to the presence or absence of traumatic cues or reminders, limits the applicability and validity of behavioral outcome measures. Neuroimaging and cognitive markers can contribute significantly to improve the reliability of attempts to apply behavioral interventions to the treatment of children diagnosed with PTSD.

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