Model-based Mind Wandering in Older Adults: Age Differences in the Behavioral and Electrophysiological Correlates of Subjective and Objective Measures of Mind Wandering.

Mind wandering is typically characterized as a failure of attentional control, yet despite age-related executive function deficits, older adults typically report less mind wandering than younger adults during cognitive tasks and in daily life. Self-reported mind wandering episodes usually result in similar behavioral detriments in younger and older adults (e.g., greater RT variability, more task errors). However, the relatively few studies investigating the neural correlates of mind wandering and aging have revealed mixed findings, possibly because they typically rely on infrequent thought probes and, therefore, few trials for neural analyses. In the current study, we propose a method to recover more task data by categorizing trials from a commonly used sustained attention to response task according to RT variability. Behavioral data (n = 49 younger; n = 40 older) revealed that compared with younger adults, older adults reported fewer mind wandering episodes, but showed similar behavioral impacts thereof. Furthermore, in both age groups, subjective reports of mind wandering predicted the more objective sorting of trials into "on-" and "off-task" according to RT variability. Using these objectively sorted trials, we investigated two commonly reported EEG measures of mind wandering (diminished P1 and P3 amplitude) in 26 younger and 24 older adults. Although the P1 did not differ between on- and off-task trials for either group, the P3 was diminished for off-task trials in both age groups (albeit significantly less in older adults) suggesting preserved perceptual but reduced higher-order processing during off-task periods in both groups.

Decreased Temporomandibular Joint Range of Motion in a Model of Early Osteoarthritis in the Rabbit.

PURPOSE: Analysis of mandibular biomechanics could help with understanding the mechanisms of temporomandibular joint (TMJ) disorders (TMJDs), such as osteoarthritis (TMJ-OA), by investigating the effects of injury or disease on TMJ movement. The objective of the present study was to determine the functional kinematic implications of mild TMJ-OA degeneration caused by altered occlusion from unilateral splints in the rabbit. MATERIALS AND METHODS: Altered occlusion of the TMJ was mechanically induced in rabbits by way of a unilateral molar dental splint (n = 3). TMJ motion was assessed using 3-dimensional (3D) skeletal kinematics twice, once before and once after 6 weeks of splint placement with the splints removed, after allowing 3 days of recovery. The relative motion of the condyle to the fossa and the distance between the incisors were tracked. RESULTS: An overall decrease in the range of joint movement was observed at the incisors and in the joint space between the condyle and fossa. The incisor movement decreased from 7.0 ± 0.5 mm to 6.2 ± 0.5 mm right to left, from 5.5 ± 2.2 mm to 4.6 ± 0.8 mm anterior to posterior, and from 13.3 ± 1.8 mm to 11.6 ± 1.4 mm superior to inferior (P < .05). The total magnitude of the maximum distance between the points on the condyle and fossa decreased from 3.6 ± 0.8 mm to 3.1 ± 0.6 mm for the working condyle and 2.8 ± 0.4 mm to 2.5 ± 0.4 mm for the balancing condyle (P < .05). The largest decreases were seen in the anteroposterior direction for both condyles. CONCLUSION: Determining the changes in condylar movement might lead to a better understanding of the early predictors in the development of TMJ-OA and determining when the symptoms become a chronic, irreversible problem.

BMP-2-regenerated calvarial bone: a biomechanical appraisal in a large animal model.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is gaining popularity in craniofacial applications. Calvarial defects are, under normal circumstances, subjected to only minimal levels of the biomechanical stresses known to play an important role in osteogenesis, yet regenerated calvarial bone must be capable of withstanding traumatic forces such that the underlying neurocapsule is protected. The aim of this study is to, for the first time, assess the biomechanical properties of calvarial bone regenerated with derivations of a commercially available rhBMP-2-based system. Standardized calvarial defects were created in 23 adult male canines. These defects were treated with rhBMP-2 on one of several carriers. After 24 weeks, the biomechanical properties of the rhBMP-2-generated bone were compared to those of controls with a modified punch-out test (Bluehill 2; Instron, Norwood, Mass) and compared using a paired nonparametric analyses (SPSS, 17.0, Chicago, Ill). In a previously published report, defects across all the rhBMP-2 therapy groups were observed to have a mean rate of 99.5% radio-opacity at 24 weeks indicating nearly full bony coverage of the calvarial defect (compared to 32.7% in surgical controls). For ultimate load, ultimate energy, and first peak energy, there were significant differences (P<0.05) with the control native bone having more robust biomechanical properties than the rhBMP-2-generated bone. We conclude from these findings that rhBMP-2-generated calvarial bone is significantly less protective against trauma than native bone at 6 months. Further investigation is required to assess the efficacy of rhBMP-2 in healing calvarial defects in the longer term.

Shift happens: aging alters the content but not the organization of memory for complex events.

While cognitive aging research has compared episodic memory accuracy between younger and older adults, less work has described differences in how memories are encoded and recalled. This is important for memories of real-world experiences, since there is immense variability in which details can be accessed and organized into narratives. We investigated age effects on the organization and content of memory for complex events. In two independent samples (N = 45; 60), young and older adults encoded and recalled the same short-movie. We applied a novel scoring on the recollections to quantify recall accuracy, temporal organization (temporal contiguity, forward asymmetry), and content (perceptual, conceptual). No age-effects on recall accuracy nor on metrics of temporal organization emerged. Older adults provided more conceptual and non-episodic content, whereas younger adults reported a higher proportion of event-specific information. Our results indicate that age-related differences in episodic recall reflect distinctions in what details are assembled from the past.

Na+/H+ exchanger regulatory factor 1 (NHERF1) directly regulates osteogenesis.

Bone formation requires synthesis, secretion, and mineralization of matrix. Deficiencies in these processes produce bone defects. The absence of the PDZ domain protein Na(+)/H(+) exchange regulatory factor 1 (NHERF1) in mice, or its mutation in humans, causes osteomalacia believed to reflect renal phosphate wasting. We show that NHERF1 is expressed by mineralizing osteoblasts and organizes Na(+)/H(+) exchangers (NHEs) and the PTH receptor. NHERF1-null mice display reduced bone formation and wide mineralizing fronts despite elimination of phosphate wasting by dietary supplementation. Bone mass was normal, reflecting coordinated reduction of bone resorption and formation. NHERF1-null bone had decreased strength, consistent with compromised matrix quality. Mesenchymal stem cells from NHERF1-null mice showed limited osteoblast differentiation but enhanced adipocyte differentiation. PTH signaling and Na(+)/H(+) exchange were dysregulated in these cells. Osteoclast differentiation from monocytes was unaffected. Thus, NHERF1 is required for normal osteoblast differentiation and matrix synthesis. In its absence, compensatory mechanisms maintain bone mass, but bone strength is reduced.

Counterfactual thinking and reward processing: an fMRI study of responses to gamble outcomes.

The process of comparing obtained outcomes to alternative possible outcomes, known as counterfactual thinking, is inescapable in daily life; however, the neurocognitive mechanisms underlying counterfactual thinking and how they influence emotional responses to better and worse outcomes is not well understood. We conducted an event-related functional magnetic resonance imaging (fMRI) gambling study in which participants were informed of two equally possible outcomes of a card gamble before they selected a card. Participants reported experiencing mixed emotions (i.e., both positive and negative affect) for disappointing wins (winning the lesser of two amounts) and relieving losses (losing the lesser of two amounts). Neuroimaging results supported the hypothesis that these mixed emotions were associated with activation of a fronto-parietal network, which subsequently influenced processing in reward and punishment regions (dorsal and ventral striatum, right anterior insula). The fronto-parietal network was sensitive to outcomes that resulted in mixed emotions, whereas reward and punishment regions were sensitive to comparisons between obtained and unobtained outcomes. These findings provide insight into the neurocognitive mechanisms underlying the mixed emotional experiences that result from counterfactual comparisons, and inform our understanding of how the brain is optimized to use the wealth of environmental information to inform current and future behavior.

Reduced distinctiveness of event boundaries in older adults with poor memory performance.

We experience the world as a continuous flow of information but segment it into discrete events in long-term memory. As a result, younger adults are more likely to recall details of an event when cued with information from the same event (within-event cues) than from the prior event (between-event cues), suggesting that stronger associations are formed within events than across event boundaries. The present study aimed to investigate the effects of age and working memory updating on this within > between cued-recall effect and the consequences for subsequent memory. Across two studies, participants viewed two different films (Hitchcock's Bang You're Dead and BBC's Sherlock). They were later shown clips taken from either the beginning/middle (within-event cues) or end (between-event cues) of a scene and asked to recall what happened next in the film. While the main effect of age was not significant in either experiment, overall memory performance related to the within > between effect in older, but not younger, adults. Low-performing older adults showed less of a difference in cued recall for within- and between-event cues than high performers. In Study 2, better two-back task performance also related to a greater within > between effect in older, but not younger, adults, suggesting that working memory updating relates to the distinctiveness of events stored in long-term memory, at least in older adults. Taken together, these findings suggest that age differences in event memory are not inevitable and may critically depend on one's ability update working memory at event boundaries. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Increased alpha suppression with age during involuntary memory retrieval.

Recent work suggests that while voluntary episodic memory declines with age, involuntary episodic memory, which comes to mind spontaneously without intention, remains relatively intact. However, the neurophysiology underlying these differences has yet to be established. The current study used electroencephalography (EEG) to investigate voluntary and involuntary retrieval in older and younger adults. Participants first encoded sounds, half of which were paired with pictures, the other half unpaired. EEG was then recorded as they listened to the sounds, with participants in the involuntary group performing a sound localization cover task, and those in the voluntary group additionally attempting to recall the associated pictures. Participants later reported which sounds brought the paired picture to mind during the localization task. Reaction times on the localization task were slower for voluntary than involuntary retrieval and for paired than unpaired sounds, possibly reflecting increased attentional demands of voluntary retrieval and interference from reactivation of the associated pictures respectively. For the EEG analyses, young adults showed greater alpha event-related desynchronization (ERD) during voluntary than involuntary retrieval at frontal and occipital sites, while older adults showed pronounced alpha ERD regardless of intention. Additionally, older adults showed greater ERD for paired than unpaired sounds at occipital sites, likely reflecting visual reactivation of the associated pictures. Young adults did not show this alpha ERD memory effect. Taken together, these data suggest that involuntary memory is largely preserved with age, but this may be due to older adults' greater recruitment of top-down control even when demand for such control is limited.

Biopsychosocial assessment criteria for functional chronic visceral pain: a pilot review of concept and practice.

UNLABELLED: Functional chronic visceral pain (FCVP) is one of the most common causes of morbidity in the general population. Pain perceived within the abdomen may occur due to a range of different mechanisms according to the organ and their afferent pathways. Advances in our understanding of the complexities of FCVP could lead to the exploitation of contemporary research in order to develop and utilize our understanding of neurobiological and psychobiological visceral mechanisms in a clinical setting. This progression, together with increasing amounts of epidemiological and gender based information concerning specific abdominal pain syndromes can allow us to develop assessment tools that go beyond disease only analysis and move toward a more comprehensive assessment model so that patients may have access to expert or multidisciplinary management sooner, rather than later. Based on current evidence, one must consider the main contributors to pain, whether it is nociceptive, neuropathic or psychosocial or as is common with FCVP, a combination of all three. AIM: This comprehensive assessment model should encompass not only systematic evaluation for reliable communication, but should also progress toward idiographic diagnosis relating to the uniqueness of the patient. This model should be practical in a multidisciplinary setting, taking into account the multi-faceted nature of this presentation.

Reduced Attentional Control in Older Adults Leads to Deficits in Flexible Prioritization of Visual Working Memory.

Visual working memory (VWM) resources have been shown to be flexibly distributed according to item priority. This flexible allocation of resources may depend on attentional control, an executive function known to decline with age. In this study, we sought to determine how age differences in attentional control affect VWM performance when attention is flexibly allocated amongst targets of varying priority. Participants performed a delayed-recall task wherein item priority was varied. Error was modelled using a three-component mixture model to probe different aspects of performance (precision, guess-rate, and non-target errors). The flexible resource model offered a good fit to the data from both age groups, but older adults showed consistently lower precision and higher guess rates. Importantly, when demands on flexible resource allocation were highest, older adults showed more non-target errors, often swapping in the item that had a higher priority at encoding. Taken together, these results suggest that the ability to flexibly allocate attention in VWM is largely maintained with age, but older adults are less precise overall and sometimes swap in salient, but no longer relevant, items possibly due to their lessened ability to inhibit previously attended information.

Associations between social jetlag and mental health in young people: A systematic review.

Adolescence and early adulthood (collectively categorized as "young people") is a transitional period associated with a number of key physiological, social and psychological changes. Sleep difficulties, notable in this age group, may adversely affect physical and mental health. Of interest is the impact of the natural shift in young people towards a more evening-type sleep pattern (chronotype), whilst social constraints encourage early waking to fit with school/work timings. This leads to a misalignment in sleep timing between weekdays and weekends, known as social jetlag, which may contribute to emerging mental health difficulties seen during this age group. A systematic literature review was undertaken to investigate the association between social jetlag and mental health outcomes. Systematic searching of electronic databases (The Cochrane Library; PsycINFO; CINAHL; Scopus; and PubMed), grey literature and review of reference lists identified seven studies which assessed associations between social jetlag and mental health outcomes in young people. Quality appraisal was completed using the Appraisal Tool for Cross-Sectional Studies. Findings appeared equivocal; however significant associations were revealed with social jetlag associated with clinical depression and seasonal depression, in female participants and high latitude regions. Quality of included studies was moderate (10-13 criteria met). A lack of homogeneity between study methodologies precluded the conduct of a meta-analysis. The ambiguous results found may result from confounding factors including non-comparable methods of measuring social jetlag and mental health both in this age group and the selected studies. Future research should address a lack of homogeneity through the development of an interdisciplinary core outcome set, and agreement on a standardized measure and calculation for social jetlag.

Parenting stress and childhood epilepsy: the impact of depression, learning, and seizure-related factors.

OBJECTIVE: The purpose of this study was to evaluate stress in parents of children with epilepsy relative to the impact of childhood depression, learning disorders, and seizure-related risk factors. METHODS: Sixty-five parents and their children completed the Parenting Stress Index, Child Depression Inventory, and behavior and demographic forms. Kruska-Wallis ANOVAs and Spearman's rank correlations were used in a cross-sectional study design. RESULTS: High levels of stress were found among the parents (45%). Overall, child depression (23%) was found to significantly increase the distress parents experienced in their role (P<0.05). Another risk factor found to impact parenting stress was learning disabilities (P<0.01). The seizure-related factors of polytherapy, duration, and age at onset were correlated with depression (P<0.05). CONCLUSION: To effectively manage children with epilepsy, assessments of depression and learning must be considered because of their potential impact on parenting stress and the child's overall quality of life.

Biomechanical Integrity in Craniofacial Surgery: Calvarial Reconstruction in Favorable and Infected Defects with Bone Morphogenetic Protein 2.

BACKGROUND: The limitations of autologous and alloplastic reconstruction for craniofacial bone defects have created a clinical need for viable tissue-engineering strategies. Recombinant human bone morphogenetic protein-2 (rhBMP-2) has shown promise in this setting. The aim of this study was to determine the long-term biomechanical properties of rhBMP-2-mediated calvarial reconstruction. METHODS: Twelve-week-old New Zealand White rabbits underwent subtotal calvarectomy. Defects were repaired in one of several groups: immediate reconstruction with autologous graft, immediate reconstruction with cryopreserved bone graft, immediate reconstruction with rhBMP-2 (favorable), and delayed reconstruction with rhBMP-2 following infection and subsequent débridement (unfavorable). Cryopreserved reconstructions were measured at 6 weeks; autologous reconstructions were measured at 6 weeks and 6 months; and both favorable and unfavorable rhBMP-2 reconstructions were assessed at 6 weeks, 6 months, and 1 year after reconstruction. Healing was assessed with computed tomography. An unconfined compression test was performed for biomechanical analysis. Stress at 20 percent strain, percentage relaxation, tangent modulus, and final strain at 1800 N were compared between groups. RESULTS: Nearly complete radiographic coverage was achieved by 6 months for autologous reconstruction and by 6 weeks for rhBMP-2 reconstruction. Favorable rhBMP-2 reconstruction demonstrated a larger final strain at 1800 N through 1 year compared with native bone. Bone in unfavorable rhBMP-2 reconstruction was more compressible than native bone, with a larger final strain at 1800 N at 1 year. There were no significant differences between favorable and unfavorable groups. CONCLUSIONS: Despite providing radiographic coverage, the biomechanical properties of rhBMP-2 bone differ from those of native bone. Further studies are warranted to determine how these properties affect overall strength and structural integrity.

Neural correlates of self-perceptions in adolescents with major depressive disorder.

Alteration in self-perception is a salient feature in major depression. Hyperactivity of anterior cortical midline regions has been implicated in this phenomenon in depressed adults. Here, we extend this work to depressed adolescents during a developmental time when neuronal circuitry underlying the sense of self matures by using task-based functional magnetic resonance imaging (fMRI) and connectivity analyses. Twenty-three depressed adolescents and 18 healthy controls (HC) viewed positive and negative trait words in a scanner and judged whether each word described them ('self' condition) or was a good trait to have ('general' condition). Self-perception scores were based on participants' endorsements of positive and negative traits during the fMRI task. Depressed adolescents exhibited more negative self-perceptions than HC. Both groups activated cortical midline regions in response to self-judgments compared to general-judgments. However, depressed adolescents recruited the posterior cingulate cortex/precuneus more for positive self-judgments. Additionally, local connectivity of the dorsal medial prefrontal cortex was reduced during self-reflection in depressed adolescents. Our findings highlight differences in self-referential processing network function between depressed and healthy adolescents and support the need for further investigation of brain mechanisms associated with the self, as they may be paramount to understanding the etiology and development of major depressive disorder.

Temporomandibular joint fibrocartilage degeneration from unilateral dental splints.

OBJECTIVE: The objective of this study was to determine the extent to which altered loading in the temporomandibular joint (TMJ), as might be associated with a malocclusion, drives degeneration of articulating surfaces in the TMJ. We therefore sought to quantify the effects of altered joint loading on the mechanical properties and biochemical content and distribution of TMJ fibrocartilage in the rabbit. DESIGN: Altered TMJ loading was induced with a 1mm splint placed unilaterally over the maxillary and mandibular molars for 6 weeks. At that time, TMJ fibrocartilage was assessed by compression testing, biochemical content (collagen, glycosaminoglycan (GAG), DNA) and distribution (histology), for both the TMJ disc and the condylar fibrocartilage. RESULTS: There were no changes in the TMJ disc for any of the parameters tested. The condylar fibrocartilage from the splinted animals was significantly stiffer and the DNA content was significantly lower than that in control animals. There was significant remodeling in the condylar fibrocartilage layers as manifested by a change in GAG and collagen II distribution and a loss of defined cell layers. CONCLUSIONS: A connection between the compressive properties of TMJ condylar fibrocartilage after 6 weeks of splinting and the changes in histology was observed. These results suggest a change in joint loading leads to condylar damage, which may contribute to pain associated with at least some forms of TMJ disease.

Analysis of pain in the rabbit temporomandibular joint after unilateral splint placement.

AIMS: To determine whether behavioral, anatomical, and physiologic endpoints widely used to infer the presence of pain in rodent models of temporomandibular disorders (TMD) were applicable to the rabbit model of TMD associated with altered joint loading. METHODS: Unilateral molar dental splints were used to alter temporomandibular joint (TMJ) loading. Changes in nociceptive threshold were assessed with a mechanical probing of the TMJ region on nine splinted and three control rabbits. Fos-like immunoreacitivty in the trigeminal subnucleus caudalis was assessed with standard immunohistochemical techniques from three splinted and six control animals. Retrogradely labeled TMJ afferents were studied with patch-clamp electrophysiologic techniques from three splinted and three control animals. Remodeling of TMJ condyles was assessed by histologic investigations of three splinted and three control animals. A Student t test or a Mann-Whitney U test was used with significance set at P < .05 to compare splinted to control samples. RESULTS: While variable, there was an increase in mechanical sensitivity in splinted rabbits relative to controls. The increase in Fos+ cells in splinted rabbits was also significant relative to naïve controls (86 ± 8 vs 64 ± 15 cells/section, P < .05). The rheobase (364 ± 80 pA) and action potential threshold (-31.2 ± 2.0 mV) were higher in TMJ afferents from splinted rabbits compared to controls (99 ± 22 pA and -38.0 ± 2.0 mV, P < .05). There was significant remodeling in the condylar fibrocartilage layers as manifested by a change in glycosaminoglycan distribution and a loss of defined cell layers. CONCLUSION: Behavioral and anatomical results were consistent with an increase in nociceptive signaling in concert with condylar remodeling driven by altered TMJ loading. Changes in excitability and action potential waveform were consistent with possible compensatory changes of TMJ afferents for an overall increase in afferent drive associated with joint degeneration. These compensatory changes may reflect pain-adaption processes that many patients with TMJ disorders experience.

Functional analysis of the rabbit temporomandibular joint using dynamic biplane imaging.

The dynamic function of the rabbit temporomandibular joint (TMJ) was analyzed through non-invasive, three-dimensional skeletal kinematics, providing essential knowledge for understanding normal joint motion. The objective of this study was to evaluate and determine repeatable measurements of rabbit TMJ kinematics. Maximal distances, as well as paths were traced and analyzed for the incisors and for the condyle-fossa relationship. From one rabbit to another, the rotations and translations of both the incisors and the condyle relative to the fossa contained multiple clear, repeatable patterns. The slope of the superior/inferior incisor distance with respect to the rotation about the transverse axis was repeatable to 0.14 mm/deg and the right/left incisor distance with respect to the rotation about the vertical axis was repeatable to 0.03 mm/deg. The slope of the superior/inferior condylar translation with respect to the rotational movement about the transverse axis showed a consistent relationship to within 0.05 mm/deg. The maximal translations of the incisors and condyles were also consistent within and between rabbits. With an understanding of the normal mechanics of the TMJ, kinematics can be used to compare and understand TMJ injury and degeneration models.

The neural correlates of emotional face-processing in adolescent depression: a dimensional approach focusing on anhedonia and illness severity.

Deficits in emotion processing, a known clinical feature of major depressive disorder (MDD), have been widely investigated using emotional face paradigms and neuroimaging. However, most studies have not accounted for the high inter-subject variability of symptom severity. Similarly, only sparse research has focused on MDD in adolescence, early in the course of the illness. Here we sought to investigate neural responses to emotional faces using both categorical and dimensional analyses with a focus on anhedonia, a core symptom of MDD associated with poor outcomes. Nineteen medication-free depressed adolescents and 18 healthy controls (HC) were scanned during presentation of happy, sad, fearful, and neutral faces. ANCOVAs and regressions assessed group differences and relationships with illness and anhedonia severity, respectively. Findings included a group by valence interaction with depressed adolescents exhibiting decreased activity in the superior temporal gyrus (STG), putamen and premotor cortex. Post-hoc analyses confirmed decreased STG activity in MDD adolescents. Dimensional analyses revealed associations between illness severity and altered responses to negative faces in prefrontal, cingulate, striatal, and limbic regions. However, anhedonia severity was uniquely correlated with responses to happy faces in the prefrontal, cingulate, and insular regions. Our work highlights the need for studying specific symptoms dimensionally in psychiatric research.

Magnesium alloys as a biomaterial for degradable craniofacial screws.

Recently, magnesium (Mg) alloys have received significant attention as potential biomaterials for degradable implants, and this study was directed at evaluating the suitability of Mg for craniofacial bone screws. The objective was to implant screws fabricated from commercially available pure Mg and alloy AZ31 in vivo in a rabbit mandible. First, Mg and AZ31 screws were compared to stainless steel screws in an in vitro pull-out test and determined to have a similar holding strength (∼40N). A finite-element model of the screw was created using the pull-out test data, and this model can be used for future Mg alloy screw design. Then, Mg and AZ31 screws were implanted for 4, 8 and 12weeks, with two controls of an osteotomy site (hole) with no implant and a stainless steel screw implanted for 12weeks. Microcomputed tomography was used to assess bone remodeling and Mg/AZ31 degradation, both visually and qualitatively through volume fraction measurements for all time points. Histological analysis was also completed for the Mg and AZ31 at 12weeks. The results showed that craniofacial bone remodeling occurred around both Mg and AZ31 screws. Pure Mg had a different degradation profile than AZ31; however, bone growth occurred around both screw types. The degradation rate of both Mg and AZ31 screws in the bone marrow space and the muscle were faster than in the cortical bone space at 12weeks. Furthermore, it was shown that by alloying Mg, the degradation profile could be changed. These results indicate the promise of using Mg alloys for craniofacial applications.

A preliminary study of white matter in adolescent depression: relationships with illness severity, anhedonia, and irritability.

Major depressive disorder (MDD) during adolescence is a common and disabling psychiatric condition; yet, little is known about its neurobiological underpinning. Evidence indicates that MDD in adults involves alterations in white and gray matter; however, sparse research has focused on adolescent MDD. Similarly, little research has accounted for the wide variability of symptom severity among depressed teens. Here, we aimed to investigate white matter (WM) microstructure between 17 adolescents with MDD and 16 matched healthy controls (HC) using diffusion tensor imaging. We further assessed within the MDD group relationships between WM integrity and depression severity, as well as anhedonia and irritability - two core symptoms of adolescent MDD. As expected, adolescents with MDD manifested decreased WM integrity compared to HC in the anterior cingulum and anterior corona radiata. Within the MDD group, greater depression severity was correlated with reduced WM integrity in the genu of corpus callosum, anterior thalamic radiation, anterior cingulum, and sagittal stratum. However, anhedonia and irritability were associated with alterations in distinct WM tracts. Specifically, anhedonia was associated with disturbances in tracts related to reward processing, including the anterior limb of the internal capsule and projection fibers to the orbitofrontal cortex. Irritability was associated with decreased integrity in the sagittal stratum, anterior corona radiata, and tracts leading to prefrontal and temporal cortices. Overall, these preliminary findings provide further support for the hypotheses that there is a disconnect between prefrontal and limbic emotional regions in depression, and that specific clinical symptoms involve distinct alterations in WM tracts.