Posttraumatic Stress Disorder Subsequent to Apparent Mild Traumatic Brain Injury.

Posttraumatic stress disorder (PTSD) is prevalent among veterans with a history of traumatic brain injury (TBI); however, the relationship between TBI and PTSD is not well understood. We present the case of a 31-year-old male veteran with PTSD who reported TBI before entering the military. The reported injury appeared to be mild: He was struck on the head by a baseball, losing consciousness for ∼10 seconds. Years later, he developed severe PTSD after combat exposure. He was not receiving clinical services for these issues but was encountered in the context of a research study. We conducted cognitive, autonomic, and MRI assessments to assess brain function, structure, and neurophysiology. Next, we compared amygdala volume, uncinate fasciculus diffusion, functional connectivity, facial affect recognition, and baroreceptor coherence with those of a control group of combat veterans (n = 23). Our veteran's MRI revealed a large right medial-orbital prefrontal lesion with surrounding atrophy, which the study neuroradiologist interpreted as likely caused by traumatic injury. Comparison with controls indicated disrupted structural and functional connectivity of prefrontal-limbic structures and impaired emotional, cognitive, and autonomic responses. Detection of this injury before combat would have been unlikely in a clinical context because our veteran had reported a phenomenologically mild injury, and PTSD is a simple explanation for substance abuse, sleep impairment, and psychosocial distress. However, it may be that right prefrontal-limbic disruption imparted vulnerability for the development of PTSD and exacerbated our veteran's emotional response to, and recovery from, PTSD.

The influence of traumatic brain injury on the allocation of vertical spatial attention.

Objective: Research on impairments of spatial attention has primarily investigated hemispatial neglect in brain-lesioned patients, revealing decrements in the allocation of attention to right versus left egocentric or allocentric hemispace. Whereas head trauma might injure those parts of the brain that allocate vertical attention, little is known about the influence of trauma on the allocation of visuospatial attention in vertical space. Thus, the goal of this study was to learn if chronic moderate-to-severe traumatic brain injury (m/sTBI) alters the allocation of vertical visuospatial attention as assessed by the Attention Network Task (ANT). The ANT assesses the influence of Posner-type spatial cues and distractors using an Eriksen flanker task.Methods: 12 chronic m/sTBI patients and 12 demographically-matched neurologically-healthy controls (HCs) completed a version of the ANT wherein trials were coded for cue and target locations above and below central visual fixation. Trial-wise reaction times (RT) and accuracy were subjected to mixed-model ANOVAs and planned contrasts.Results: These data were subject to secondary analyses, which revealed that across groups, median RTs were significantly faster when targets occurred above than below the central visual fixation (p < .01); however, only HCs' error rates differed as a function of target altitude. Unlike controls, m/sTBI survivors did not exhibit the anticipated upward error-rate attentional bias.Conclusions: As alteration of spatial attention can be a major cause of disability, present findings suggest that m/sTBI survivors exhibit this loss of normal upward attentional bias. Future studies are need to learn if these patients might benefit from treatment.

Easily detected signs of perineural tumour spread in head and neck cancer.

Perineural tumour spread (PNTS) in head and neck oncology is most often caused by squamous cell carcinoma. The most frequently affected nerves are the trigeminal and facial nerves. Up to 40% of patients with PNTS may be asymptomatic. Therefore, the index of suspicion should be high when evaluating imaging studies of patients with head and neck cancer. This review describes a "quick search checklist" of easily detected imaging signs of PNTS. TEACHING POINTS: • A distinctive feature of head and neck tumours is growth along nerves. • Perineural tumour spread is most often caused by squamous cell carcinoma. • There are several key findings for the detection of perineural tumour spread.

Practical Tips for MR Imaging of Perineural Tumor Spread.

Perineural tumor spread (PNS) substantially alters a patient's prognosis and treatment plan. Therefore, it is critical that the radiologists are familiar with the course of cranial nerves commonly affected by PNS and the neuronal connections to appropriately map the extent of PNS. Limited involvement of a nerve by PNS might be resectable, whereas advanced PNS may require radiation therapy.

Thoracoscopic Ablation With Appendage Ligation Versus Medical Therapy for Stroke Prevention: A Proof-of-Concept Randomized Trial.

OBJECTIVE: Atrial fibrillation (AF) has a demonstrable effect on quality of life (QOL). Recurrent stroke occurs in 10% of patients with AF. The objective of this study was to demonstrate proof of concept that thoracoscopic pulmonary vein isolation and atrial appendage ligation (TPVIAL) could prevent recurrent stroke and could potentially improve QOL in patients with AF with a previous stroke. METHODS: The study was a National Institutes of Health-funded single-center proof-of-concept design that randomized 23 patients with AF-related stroke to TPVIAL (n = 12) or to medical management (n = 11). Quality of life was the primary outcome variable; secondary end points included restoration of rhythm, recurrent stroke, and surgical morbidity. RESULTS: Quality-of-life subscores at 3 and 6 months revealed improvements in energy and decreases in fatigue in the TPVIAL arm [baseline, 33 (19.8); 3 months, 49.5 (20.6), P = 0.01; 6 months, 55.5 (14.4), P = 0.03]. At 12-month follow-up, there were no recurrent strokes in the TPVIAL group. In the medically treated arm, two patients at 6 months (P = 0.22) and three total patients at 12 months (P = 0.09) had recurrent ischemic stroke. There was one death in the medical management arm. In the TPVIAL arm, no AF recurrence occurred in patients with paroxysmal AF, and one patient had recurrence of persistent and long-standing AF. Seven patients in the TPVIAL arm discontinued warfarin therapy for secondary stroke prevention. CONCLUSIONS: This small proof-of-concept study showed that TPVIAL improved QOL on two subscores and restored normal sinus rhythm in all but one patient, and it showed the potential to prevent secondary stroke. A larger study will be needed.

Dissociating Statistically-Determined Alzheimer's Disease/Vascular Dementia Neuropsychological Syndromes Using White and Gray Neuroradiological Parameters.

BACKGROUND: There is remarkable heterogeneity in clinical Alzheimer's disease (AD) or vascular dementia (VaD). OBJECTIVES: 1) To statistically examine neuropsychological data to determine dementia subgroups for individuals clinically diagnosed with AD or VaD and then 2) examine group differences in specific gray/white matter regions of interest. METHODS: A k-means cluster analysis requested a 3-group solution from neuropsychological data acquired from individuals diagnosed clinically with AD/VaD. MRI measures of hippocampal, caudate, ventricular, subcortical lacunar infarction, whole brain volume, and leukoaraiosis (LA) were analyzed. Three regions of LA volumes were quantified and these included the periventricular (5 mm around the ventricles), infracortical (5 mm beneath the gray matter), and deep (between periventricular and infracortical) regions. RESULTS: Cluster analysis sorted AD/VaD patients into single domain amnestic (n = 41), single-domain dysexecutive (n = 26), and multi-domain (n = 26) phenotypes. Multi-domain patients exhibited worst performance on language tests; however, multi-domain patients were equally impaired on memory tests when compared to amnestic patients. Statistically-determined groups dissociated using neuroradiological parameters: amnestic and multi-domain groups presented with smaller hippocampal volume while the dysexecutive group presented with greater deep, periventricular, and whole brain LA. Neither caudate nor lacunae volume differed by group. Caudate nucleus volume negatively correlated with total LA in the dysexecutive and multi-domain groups. CONCLUSIONS: There are at least three distinct subtypes embedded within patients diagnosed clinically with AD/VaD spectrum dementia. We encourage future research to assess a) the neuroradiological substrates underlying statistically-determined AD/VaD spectrum dementia and b) how statistical modeling can be integrated into existing diagnostic criteria.

Proof of principle: Transformation approach alters caudate nucleus volume and structure-function associations.

Brain magnetic resonance image (MRI) registration alters structure orientation, size, and/or shape. To determine whether linear registration methods (image transformation to 6, 9, and 12° of freedom) alter structural volume and cognitive associations, we examined transformation alterations to the caudate nucleus within individuals diagnosed with Parkinson's disease (PD) and demographically matched non-PD peers. Volumes from native and six were expected be significantly different from 9 and 12° of freedom methods. Caudate nucleus volumes were expected to be associated with measures of processing speed and mental flexibility, but the strength of the association based on transformation approach was unknown. MRI brain scans from individuals with Parkinson's disease (n = 40) and age-matched controls (n = 40) were transformed using 6, 9, and 12° of freedom to an average brain template. Correlations controlling for total intracranial volume assessed expected structural-behavioral associations. Volumetric: Raw 9 and 12° transformed volumes were significantly larger than native and 6° volumes. Only 9 and 12° volumes revealed group differences with PD less than controls. Intracranial volume considerations were essential for native and 6° between group comparisons. Structural-Behavioral: The 9 and 12° caudate nucleus volume transformations revealed the expected brain-behavioral associations. Linear registration techniques alter volumetric and cognitive-structure associations. The study highlights the need to communicate transformation approach and group intracranial volume considerations.

Error-related processing following severe traumatic brain injury: an event-related functional magnetic resonance imaging (fMRI) study.

Continuous monitoring of one's performance is invaluable for guiding behavior towards successful goal attainment by identifying deficits and strategically adjusting responses when performance is inadequate. In the present study, we exploited the advantages of event-related functional magnetic resonance imaging (fMRI) to examine brain activity associated with error-related processing after severe traumatic brain injury (sTBI). fMRI and behavioral data were acquired while 10 sTBI participants and 12 neurologically-healthy controls performed a task-switching cued-Stroop task. fMRI data were analyzed using a random-effects whole-brain voxel-wise general linear model and planned linear contrasts. Behaviorally, sTBI patients showed greater error-rate interference than neurologically-normal controls. fMRI data revealed that, compared to controls, sTBI patients showed greater magnitude error-related activation in the anterior cingulate cortex (ACC) and an increase in the overall spatial extent of error-related activation across cortical and subcortical regions. Implications for future research and potential limitations in conducting fMRI research in neurologically-impaired populations are discussed, as well as some potential benefits of employing multimodal imaging (e.g., fMRI and event-related potentials) of cognitive control processes in TBI.

Petrous apex.

The petrous apex is the most medial portion of the temporal bone that cannot be directly examined on clinical examination. The referring physician completely relies on imaging and radiologic interpretation. Unfortunately, the petrous apex displays anatomic variations such as asymmetric pneumatization that might be mistaken for underlying lesions. The location of the petrous apex also typically precludes safe percutaneous biopsy. Knowledge of the petrous apex anatomy, normal anatomic variations, and their differentiating features from pathologic entities is critical for accurate interpretation.

Double jeopardy! The additive consequences of negative affect on performance-monitoring decrements following traumatic brain injury.

Survivors of severe traumatic brain injury (TBI) are at increased risk for emotional sequelae. The current study utilized the error-related negativity (ERN) and posterror positivity (Pe) components of the event-related potential (ERP) to test the hypothesis that negative affect disproportionately impairs performance-monitoring following severe TBI. High-density ERPs were acquired while 20 survivors of severe TBI and 20 demographically matched controls performed a single-trial Stroop task. Response-locked ERPs were separately averaged for correct and error trials. Negative affect was measured as the single latent factor of measures of depression and anxiety. Groups did not differ on overall level of negative affect. Control and TBI participants did not differ on error rates as a function of negative affect, but differed in response times. ERP results revealed disproportionately smaller ERN amplitudes in participants with TBI relative to controls as a function of negative affect. Pe amplitude did not differ between groups. Negative affect inversely correlated with ERN amplitude in TBI but not control participants. Overall, results support a "double jeopardy" hypothesis of disproportionate impairments in performance monitoring when negative affect is overlaid on severe TBI.

Reliability of tumor volume estimation from MR images in patients with malignant glioma. Results from the American College of Radiology Imaging Network (ACRIN) 6662 Trial.

Reliable assessment of tumor growth in malignant glioma poses a common problem both clinically and when studying novel therapeutic agents. We aimed to evaluate two software-systems in their ability to estimate volume change of tumor and/or edema on magnetic resonance (MR) images of malignant gliomas. Twenty patients with malignant glioma were included from different sites. Serial post-operative MR images were assessed with two software systems representative of the two fundamental segmentation methods, single-image fuzzy analysis (3DVIEWNIX-TV) and multi-spectral-image analysis (Eigentool), and with a manual method by 16 independent readers (eight MR-certified technologists, four neuroradiology fellows, four neuroradiologists). Enhancing tumor volume and tumor volume plus edema were assessed independently by each reader. Intraclass correlation coefficients (ICCs), variance components, and prediction intervals were estimated. There were no significant differences in the average tumor volume change over time between the software systems (p > 0.05). Both software systems were much more reliable and yielded smaller prediction intervals than manual measurements. No significant differences were observed between the volume changes determined by fellows/neuroradiologists or technologists.Semi-automated software systems are reliable tools to serve as outcome parameters in clinical studies and the basis for therapeutic decision-making for malignant gliomas, whereas manual measurements are less reliable and should not be the basis for clinical or research outcome studies.

Skull base: pseudolesion or true lesion?

The skull base is a complex anatomical structure. Therefore, radiologists often use "side-to-side" comparison for detection of abnormalities. This approach is compromised by the high frequency of anatomical variations involving the skull base and the common presence of flow-related artifacts within vessels at the skull base that might mimic true lesions. The spectrum of "pseudolesions" ranging from different anatomical variations, such as unusual arachnoid granulations, asymmetric pneumatization and/or appearance of neurovascular foramina, to flow-related artifacts will be discussed in this review article, and tips for their distinction from a true lesion in a similar location will be given.

Pituitary abnormalities in Prader-Willi syndrome and early onset morbid obesity.

Prader-Willi syndrome (PWS) is a well-defined syndrome of childhood-obesity which can serve as a model for investigating early onset childhood obesity. Many of the clinical features of PWS (e.g., hyperphagia, hypogonadotropic hypogonadism, growth hormone deficiency) are hypothesized to be due to abnormalities of the hypothalamus and/or pituitary gland. Children who become severely obese very early in life (i.e., before age 4 years) may also have a genetic etiology of their obesity, perhaps with associated neuroendocrine and hypothalamo-pituitary defects, as infants and very young children have limited access to environmental factors that contribute to obesity. We hypothesized that morphologic abnormalities of the pituitary gland would be seen in both individuals with PWS and other subjects with early onset morbid obesity (EMO). This case-control study included individuals with PWS (n = 27, age 3 months to 39 years), patients with EMO of unknown etiology (n = 16, age 4-22 years; defined as body mass index greater than the 97th centile for age before age 4 years), and normal weight siblings (n = 25, age 7 months to 43 years) from both groups. Participants had 3-dimensional magnetic resonance imaging to evaluate the pituitary gland, a complete history and physical examination, and measurement of basal pituitary hormones. Subjects with PWS and EMO had a higher prevalence of pituitary morphological abnormalities than did control subjects (74% PWS, 69% EMO, 8% controls; P < 0.001). Anterior pituitary hormone deficiencies were universal in individuals with PWS (low IGF-1 in 100%, P < 0.001 PWS vs. controls; central hypothyroidism in 19%, P = 0.052, and hypoplastic genitalia or hypogonadotropic hypogonadism in 100%, P < 0.001), and was often seen in individuals with EMO (6%, P = 0.89 vs. control, 31%, P = 0.002, and 25%, P = 0.018, respectively). The presence of a hypoplastic pituitary gland appeared to correlate with the presence of anterior pituitary hormone deficiencies in individuals with EMO, but no correlation was apparent in individuals with PWS. In conclusion, the high frequency of both morphological and hormonal abnormalities of the pituitary gland in both individuals with PWS and EMO suggests that abnormalities in the hypothalamo-pituitary axis are features not only of PWS, but also frequently of EMO of unknown etiology.

Performance monitoring, error processing, and evaluative control following severe TBI.

Patients with severe traumatic brain injury (TBI) often demonstrate impairments in performance monitoring--an evaluative control process that can be measured using the error-negativity/error-related negativity (Ne/ERN) and post-error positivity (Pe). The Ne/ERN and Pe are event-related potential (ERP) components generated following errors, with current theories suggesting the Ne/ERN reflects automatic performance monitoring and the Pe reflects error processing and awareness. To elucidate the electrophysiological mechanisms of performance monitoring deficits following severe TBI, behavioral and ERP measurements were obtained, whereas participants with severe TBI and neurologically-healthy comparison participants performed a modified color-naming version of the Stroop task. Behaviorally, both groups demonstrated robust response-time (RT) and error-rate interference. Participants with TBI exhibited generalized RT slowing; no significant between-groups interactions were present for RTs or error rates. ERP results indicate Ne/ERN amplitude was attenuated in participants with TBI, whereas the pattern of Pe amplitude did not clearly differentiate groups. Findings suggest the Ne/ERN as a potential electrophysiological marker of evaluative control/performance monitoring impairment following TBI. Implications for future research and potential clinical application as well as potential limitations in conducting electrophysiological research in neurologically-impaired populations are discussed.

Radiotherapy and concomitant intraarterial cisplatin (RADPLAT) for advanced squamous cell carcinomas of the head and neck.

PURPOSE: Review of the University of Florida experience in treating advanced squamous cell carcinomas of the head and neck with concurrent intraarterial cisplatin and radiotherapy (RADPLAT). PATIENTS AND METHODS: Thirty-five patients with Stage III or IV head and neck squamous cell carcinomas were treated between November 2000 and October 2001 with 3 to 4 cycles of weekly intraarterial cisplatin (150 mg/m2) and a rapid infusion of the neutralizing agent sodium thiosulfate (9 g/m2), followed by a continuous infusion of sodium thiosulfate (12 g/m2), with concomitant radiotherapy (RT). The primary site was treated with 70 Gy in 35 fractions with 6 MV photons, and the low neck received 50 to 70 Gy depending on nodal involvement. Median follow-up for all patients was 4.06 years; median follow-up for living patients was 4.34 years. RESULTS: The 4-year outcomes were: local-regional control, 78%; distant metastasis-free survival, 83%; cause-specific survival, 65%; and survival, 57%. The majority of patients with recurrent disease failed at the primary site (73%); the remaining 27% of patients with recurrent disease failed only in distant sites. Nine patients required a neck dissection after chemoradiation because of suspected residual disease; 2 of 9 patients had residual tumor in the neck nodes. Severe osteoradionecrosis occurred in 26% of patients, and 9 of 35 patients (26%) required a permanent gastrostomy. CONCLUSIONS: RADPLAT results in excellent local-regional control and survival in patients with advanced squamous cell carcinomas of the head and neck. Outcomes from the University of Florida are comparable to those reported by other institutions. However, in our limited experience, the likelihood of osteoradionecrosis and permanent gastrostomy may be higher than what might be anticipated after RT alone or combined with intravenous chemotherapy.

Reward context sensitivity impairment following severe TBI: an event-related potential investigation.

Many rehabilitation protocols following traumatic brain injury (TBI) utilize reinforcement and reward to influence behavior and facilitate recovery; however, previous studies suggest survivors of severe TBI demonstrate impairments in contingency utilization and sensitivity. The precise neurobiological mechanisms underlying these deficits have not been thoroughly explored, but can be examined using the "feedback-related negativity" (FRN)--an event-related potential (ERP) component evoked following performance or response feedback (e.g., whether a monetary reward is obtained) with a larger FRN following unfavorable than favorable outcomes--particularly when unfavorable feedback occurs in the context of high reward probability. We examined ERPs elicited by favorable (monetary gain: "reward") and unfavorable (no monetary gain: "non-reward") feedback during a guessing task where probability of reward outcome was manipulated in survivors of severe TBI and demographically matched healthy participants. Consistent with previous findings, controls showed larger amplitude FRN to non-reward feedback and the largest amplitude FRN following a non-reward when reward probability context was greatest. In contrast, FRN in TBI participants did not significantly differentiate non-reward from reward trials and their FRN was largest to reward trials in the low reward probability context. Findings implicate an electrophysiological marker of impaired reward context sensitivity following severe TBI.

Evaluation of intraaxial enhancing brain tumors on magnetic resonance imaging: intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine for visualization and assessment, and implications for surgical intervention.

OBJECT: The goal in this article was to compare 0.1 mmol/kg doses of gadobenate dimeglumine (Gd-BOPTA) and gadopentetate dimeglumine, also known as gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), for enhanced magnetic resonance (MR) imaging of intraaxial brain tumors. METHODS: Eighty-four patients with either intraaxial glioma (47 patients) or metastasis (37 patients) underwent two MR imaging examinations at 1.5 tesla, one with Gd-BOPTA as the contrast agent and the other with Gd-DTPA. The interval between fully randomized contrast medium administrations was 2 to 7 days. The T1-weighted spin echo and T2-weighted fast spin echo images were acquired before administration of contrast agents and T1-weighted spin echo images were obtained after the agents were administered. Acquisition parameters and postinjection acquisition times were identical for the two examinations in each patient. Three experienced readers working in a fully blinded fashion independently evaluated all images for degree and quality of available information (lesion contrast enhancement, lesion border delineation, definition of disease extent, visualization of the lesion's internal structures, global diagnostic preference) and quantitative enhancement (that is, the extent of lesion enhancement after contrast agent administration compared with that seen before its administration [hereafter referred to as percent enhancement], lesion/brain ratio, and contrast/noise ratio). Differences were tested with the Wilcoxon signed-rank test. Reader agreement was assessed using kappa statistics. Significantly better diagnostic information/imaging performance (p < 0.0001, all readers) was obtained with Gd-BOPTA for all visualization end points. Global preference for images obtained with Gd-BOPTA was expressed for 42 (50%), 52 (61.9%), and 56 (66.7%) of 84 patients (readers 1, 2, and 3, respectively) compared with images obtained with Gd-DTPA contrast in four (4.8%), six (7.1%), and three (3.6%) of 84 patients. Similar differences were noted for all other visualization end points. Significantly greater quantitative contrast enhancement (p < 0.04) was noted after administration of Gd-BOPTA. Reader agreement was good (kappa > 0.4). CONCLUSIONS: Lesion visualization, delineation, definition, and contrast enhancement are significantly better after administration of 0.1 mmol/kg Gd-BOPTA, potentially allowing better surgical planning and follow up and improved disease management.

An evaluation of the variability of tumor-shape definition derived by experienced observers from CT images of supraglottic carcinomas (ACRIN protocol 6658).

PURPOSE: Accurate target definition is considered essential for sophisticated, image-guided radiation therapy; however, relatively little information has been reported that measures our ability to identify the precise shape of targets accurately. We decided to assess the manner in which eight "experts" interpreted the size and shape of tumors based on "real-life" contrast-enhanced computed tomographic (CT) scans. METHODS AND MATERIALS: Four neuroradiologists and four radiation oncologists (the authors) with considerable experience and presumed expertise in treating head-and-neck tumors independently contoured, slice-by-slice, his/her interpretation of the precise gross tumor volume (GTV) on each of 20 sets of CT scans taken from 20 patients who previously were enrolled in Radiation Therapy Oncology Group protocol 91-11. RESULTS: The average proportion of overlap (i.e., the degree of agreement) was 0.532 (95% confidence interval 0.457 to 0.606). There was a slight tendency for the proportion of overlap to increase with increasing average GTV. CONCLUSIONS: Our work suggests that estimation of tumor shape currently is imprecise, even for experienced physicians. In consequence, there appears to be a practical limit to the current trend of smaller fields and tighter margins.

Diffusion tensor imaging of frontal white matter and executive functioning in cocaine-exposed children.

BACKGROUND: Although animal studies have demonstrated frontal white matter and behavioral changes resulting from prenatal cocaine exposure, no human studies have associated neuropsychological deficits in attention and inhibition with brain structure. We used diffusion tensor imaging to investigate frontal white matter integrity and executive functioning in cocaine-exposed children. METHODS: Six direction diffusion tensor images were acquired using a Siemens 3T scanner with a spin-echo echo-planar imaging pulse sequence on right-handed cocaine-exposed (n = 28) and sociodemographically similar non-exposed children (n = 25; mean age: 10.6 years) drawn from a prospective, longitudinal study. Average diffusion and fractional anisotropy were measured in the left and right frontal callosal and frontal projection fibers. Executive functioning was assessed using two well-validated neuropsychological tests (Stroop color-word test and Trail Making Test). RESULTS: Cocaine-exposed children showed significantly higher average diffusion in the left frontal callosal and right frontal projection fibers. Cocaine-exposed children were also significantly slower on a visual-motor set-shifting task with a trend toward lower scores on a verbal inhibition task. Controlling for gender and intelligence, average diffusion in the left frontal callosal fibers was related to prenatal exposure to alcohol and marijuana and an interaction between cocaine and marijuana exposure. Performance on the visual-motor set-shifting task was related to prenatal cocaine exposure and an interaction between cocaine and tobacco exposure. Significant correlations were found between test performance and fractional anisotropy in areas of the frontal white matter. CONCLUSIONS: Prenatal cocaine exposure, alone and in combination with exposure to other drugs, is associated with slightly poorer executive functioning and subtle microstructural changes suggesting less mature development of frontal white matter pathways. The relative contribution of postnatal environmental factors, including characteristics of the caregiving environment and stressors associated with poverty and out-of-home placement, on brain development and behavioral functioning in polydrug-exposed children awaits further research.