-
Molecular Psychiatry Dec 2023Childhood trauma is a known risk factor for trauma and stress-related disorders in adulthood. However, limited research has investigated the impact of childhood trauma...
Childhood trauma is a known risk factor for trauma and stress-related disorders in adulthood. However, limited research has investigated the impact of childhood trauma on brain structure linked to later posttraumatic dysfunction. We investigated the effect of childhood trauma on white matter microstructure after recent trauma and its relationship with future posttraumatic dysfunction among trauma-exposed adult participants (n = 202) recruited from emergency departments as part of the AURORA Study. Participants completed self-report scales assessing prior childhood maltreatment within 2-weeks in addition to assessments of PTSD, depression, anxiety, and dissociation symptoms within 6-months of their traumatic event. Fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) collected at 2-weeks and 6-months was used to index white matter microstructure. Childhood maltreatment load predicted 6-month PTSD symptoms (b = 1.75, SE = 0.78, 95% CI = [0.20, 3.29]) and inversely varied with FA in the bilateral internal capsule (IC) at 2-weeks (p = 0.0294, FDR corrected) and 6-months (p = 0.0238, FDR corrected). We observed a significant indirect effect of childhood maltreatment load on 6-month PTSD symptoms through 2-week IC microstructure (b = 0.37, Boot SE = 0.18, 95% CI = [0.05, 0.76]) that fully mediated the effect of childhood maltreatment load on PCL-5 scores (b = 1.37, SE = 0.79, 95% CI = [-0.18, 2.93]). IC microstructure did not mediate relationships between childhood maltreatment and depressive, anxiety, or dissociative symptomatology. Our findings suggest a unique role for IC microstructure as a stable neural pathway between childhood trauma and future PTSD symptoms following recent trauma. Notably, our work did not support roles of white matter tracts previously found to vary with PTSD symptoms and childhood trauma exposure, including the cingulum bundle, uncinate fasciculus, and corpus callosum. Given the IC contains sensory fibers linked to perception and motor control, childhood maltreatment might impact the neural circuits that relay and process threat-related inputs and responses to trauma.
Topics: Humans; Stress Disorders, Post-Traumatic; Male; Female; Adult; Diffusion Tensor Imaging; White Matter; Internal Capsule; Child Abuse; Adult Survivors of Child Abuse; Middle Aged; Anisotropy; Brain; Depression; Anxiety; Self Report; Young Adult
PubMed: 36932158
DOI: 10.1038/s41380-023-02012-3 -
The Journal of Neuroscience : the... Apr 2022The projection neurons of the striatum, the principal nucleus of the basal ganglia, belong to one of the following two major pathways: the striatopallidal (indirect)...
The projection neurons of the striatum, the principal nucleus of the basal ganglia, belong to one of the following two major pathways: the striatopallidal (indirect) pathway or the striatonigral (direct) pathway. Striatonigral axons project long distances and encounter ascending tracts (thalamocortical) while coursing alongside descending tracts (corticofugal) as they extend through the internal capsule and cerebral peduncle. These observations suggest that striatal circuitry may help to guide their trajectories. To investigate the developmental contributions of striatonigral axons to internal capsule formation, we have made use of (striatal direct pathway) and (corticofugal pathway) BAC transgenic reporter mice in combination with immunohistochemical markers to trace these axonal pathways throughout development. We show that striatonigral axons pioneer the internal capsule and cerebral peduncle and are temporally and spatially well positioned to provide guidance for corticofugal and thalamocortical axons. Using conditional knock-out (cKO) mice, which exhibit disrupted striatonigral axon outgrowth, we observe both corticofugal and thalamocortical axon defects with either ventral forebrain- or telencephalon-specific inactivation, despite Isl1 not being expressed in either cortical or thalamic projection neurons. Striatonigral axon defects can thus disrupt internal capsule formation. Our genome-wide transcriptomic analysis in cKOs reveals changes in gene expression relevant to cell adhesion, growth cone dynamics, and extracellular matrix composition, suggesting potential mechanisms by which the striatonigral pathway exerts this guidance role. Together, our data support a novel pioneering role for the striatal direct pathway in the correct assembly of the ascending and descending axon tracts within the internal capsule and cerebral peduncle. The basal ganglia are a group of subcortical nuclei with established roles in the coordination of voluntary motor programs, aspects of cognition, and the selection of appropriate social behaviors. Hence, disruptions in basal ganglia connectivity have been implicated in the motor, cognitive, and social dysfunction characterizing common neurodevelopmental disorders such as attention-deficit/hyperactivity disorder, autism spectrum disorder, obsessive-compulsive disorder, and tic disorder. Here, we identified a novel role for the striatonigral (direct) pathway in pioneering the internal capsule and cerebral peduncle, and in guiding axons extending to and from the cortex. Our findings suggest that the abnormal development of basal ganglia circuits can drive secondary internal capsule defects and thereby may contribute to the pathology of these disorders.
Topics: Animals; Autism Spectrum Disorder; Axons; Cerebral Cortex; Cerebral Peduncle; Internal Capsule; Mice; Mice, Knockout; Mice, Transgenic; Neural Pathways; Thalamus
PubMed: 35273083
DOI: 10.1523/JNEUROSCI.2291-21.2022 -
Autism Research : Official Journal of... Mar 2018The thalamus is a key sensorimotor relay area that is implicated in autism spectrum disorder (ASD). However, it is unknown how the thalamus and white-matter structures...
UNLABELLED
The thalamus is a key sensorimotor relay area that is implicated in autism spectrum disorder (ASD). However, it is unknown how the thalamus and white-matter structures that contain thalamo-cortical fiber connections (e.g., the internal capsule) develop from childhood into adulthood and whether this microstructure relates to basic motor challenges in ASD. We used diffusion weighted imaging in a cohort-sequential design to assess longitudinal development of the thalamus, and posterior- and anterior-limbs of the internal capsule (PLIC and ALIC, respectively) in 89 males with ASD and 56 males with typical development (3-41 years; all verbal). Our results showed that the group with ASD exhibited different developmental trajectories of microstructure in all regions, demonstrating childhood group differences that appeared to approach and, in some cases, surpass the typically developing group in adolescence and adulthood. The PLIC (but not ALIC nor thalamus) mediated the relation between age and finger-tapping speed in both groups. Yet, the gap in finger-tapping speed appeared to widen at the same time that the between-group gap in the PLIC appeared to narrow. Overall, these results suggest that childhood group differences in microstructure of the thalamus and PLIC become less robust in adolescence and adulthood. Further, finger-tapping speed appears to be mediated by the PLIC in both groups, but group differences in motor speed that widen during adolescence and adulthood suggest that factors beyond the microstructure of the thalamus and internal capsule may contribute to atypical motor profiles in ASD. Autism Res 2018, 11: 450-462. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
LAY SUMMARY
Microstructure of the thalamus, a key sensory and motor brain area, appears to develop differently in individuals with autism spectrum disorder (ASD). Microstructure is important because it informs us of the density and organization of different brain tissues. During childhood, thalamic microstructure was distinct in the ASD group compared to the typically developing group. However, these group differences appeared to narrow with age, suggesting that the thalamus continues to dynamically change in ASD into adulthood.
Topics: Adolescent; Adult; Autism Spectrum Disorder; Child; Child, Preschool; Cohort Studies; Diffusion Magnetic Resonance Imaging; Humans; Internal Capsule; Longitudinal Studies; Male; Thalamus; Young Adult
PubMed: 29251836
DOI: 10.1002/aur.1909 -
Biological Psychiatry Nov 2021Deep brain stimulation is a promising therapeutic approach for patients with treatment-resistant obsessive-compulsive disorder, a condition linked to abnormalities in... (Review)
Review
Deep brain stimulation is a promising therapeutic approach for patients with treatment-resistant obsessive-compulsive disorder, a condition linked to abnormalities in corticobasal ganglia networks. Effective targets are placed in one of four subcortical areas with the goal of capturing prefrontal, anterior cingulate, and basal ganglia connections linked to the limbic system. These include the anterior limb of the internal capsule, the ventral striatum, the subthalamic nucleus, and a midbrain target. The goal of this review is to examine these 4 targets with respect to the similarities and differences of their connections. Following a review of the connections for each target based on anatomic studies in nonhuman primates, we examine the accuracy of diffusion magnetic resonance imaging tractography to replicate those connections in nonhuman primates, before evaluating the connections in the human brain based on diffusion magnetic resonance imaging tractography. Results demonstrate that the four targets generally involve similar connections, all of which are part of the internal capsule. Nonetheless, some connections are unique to each site. Delineating the similarities and differences across targets is a critical step for evaluating and comparing the effectiveness of each and how circuits contribute to the therapeutic outcome. It also underscores the importance that the terminology used for each target accurately reflects its position and its anatomic connections, so as to enable comparisons across clinical studies and for basic scientists to probe mechanisms underlying deep brain stimulation.
Topics: Animals; Deep Brain Stimulation; Humans; Internal Capsule; Obsessive-Compulsive Disorder; Subthalamic Nucleus; Ventral Striatum
PubMed: 32951818
DOI: 10.1016/j.biopsych.2020.06.031 -
PloS One 2018Emerging evidence suggests that structural brain abnormalities may play a role in the pathophysiology of melancholic depression. We set out to test whether...
Emerging evidence suggests that structural brain abnormalities may play a role in the pathophysiology of melancholic depression. We set out to test whether diffusion-derived estimates of white matter structure were disrupted in melancholia in regions underpinning psychomotor function. We hypothesized that those with melancholia (and evidencing impaired psychomotor function) would show disrupted white matter organization in internal capsule subdivisions. Diffusion magnetic resonance imaging (dMRI) data were acquired from 22 melancholic depressed, 23 non-melancholic depressed, and 29 healthy control participants. Voxel-wise fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) values were derived for anterior, posterior, and retrolenticular limbs of the internal capsule and compared between groups. Neuropsychological (reaction time) and psychomotor functioning were assessed and correlated against FA. Fractional anisotropy was distinctly increased, whilst RD was decreased, in the right anterior internal capsule in those with melancholia, compared to controls. The right anterior limb of the internal capsule correlated with clinical ratings of psychomotor disturbance, and reduced psychomotor speed was associated with increased FA values in the right retrolenticular limb in those with melancholia. Our findings highlight a distinct disturbance in the local white matter arrangement in specific regions of the internal capsule in melancholia, which in turn is associated with psychomotor dysfunction. This study clarifies the contribution of structural brain integrity to the phenomenology of melancholia, and may assist future efforts seeking to integrate neurobiological markers into depression subtyping.
Topics: Adolescent; Adult; Aged; Depressive Disorder; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Female; Humans; Internal Capsule; Linear Models; Male; Middle Aged; Multivariate Analysis; Neuropsychological Tests; Psychomotor Disorders; Severity of Illness Index; White Matter; Young Adult
PubMed: 29672517
DOI: 10.1371/journal.pone.0195672 -
Neural Plasticity 2022The electrophysiological recording can be used to quantify the clinical features of central poststroke pain (CPSP) caused by different lesion locations. We aimed to...
The electrophysiological recording can be used to quantify the clinical features of central poststroke pain (CPSP) caused by different lesion locations. We aimed to explore the relationship between clinical features and lesion location in patients with CPSP using the current perception threshold (CPT) approach. Here, patients underwent the standardized CPT measure at five detection sites on both the contralesional and ipsilesional sides, using a constant alternating-current sinusoid waveform stimulus at three frequencies: 2000 Hz, 250 Hz, and 5 Hz. 57 CPSP patients were recruited in this cross-sectional study, including 13 patients with thalamic lesions and 44 patients with internal capsule lesions. Patients with a thalamic lesion had more frequent abnormal A and C fibers than those with an internal capsule lesion (69.2% versus 36.4%, value = 0.038; 53.8% versus 63.6%, value = 0.038). The patients with internal capsule lesions had more frequent abnormal A fibers than those with thalamic lesions (53.8% versus 63.6%, value < 0.001). The sensory dysfunction in the patients with thalamic lesions was more likely to occur in the upper limbs (i.e., the shoulder ( value = 0.027) and the finger ( value = 0.040)). The lower limbs (i.e., the knee ( value = 0.040) and the toe ( value = 0.005)) were more likely to experience sensory dysfunction in the patients with internal capsule lesions. Hyperesthesia was more likely to occur in the thalamic patients, and hypoesthesia was more likely to occur in the patients with internal capsule lesions ( value < 0.001). In patients with thalamic lesions, Visual Analogue Scale (VAS) had a positive correlation with 5 Hz CPT on the shoulder ( = 0.010, value = 0.005), 250 Hz CPT on the finger ( = 0.690, value = 0.009) from the contralesional side, and 2000 Hz CPT on the knee ( = 0.690, value = 0.009). In patients with internal capsule lesions, VAS had a positive correlation with 2000 Hz CPT on the knee ( = 0.312, value = 0.039) and foot ( = 0.538, value < 0.001). In conclusion, the abnormal fiber types, sensory dysfunction territory, and clinical signs of CPSP in thalamic stroke differ from those in internal capsule stroke. Implementation of the portable and convenient CPT protocol may help clarify the locations of different stroke lesions in various clinical settings.
Topics: Cross-Sectional Studies; Humans; Neuralgia; Pain Measurement; Stroke; Thalamus
PubMed: 35707518
DOI: 10.1155/2022/1507291 -
Journal of Neurochemistry Mar 2021Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system (CNS), characterized by accumulated motor disability. However, whether...
Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system (CNS), characterized by accumulated motor disability. However, whether remyelination promotes motor recovery following demyelinating injury remains unclear. Damage to the internal capsule (IC) is known to result in motor impairment in multiple sclerosis and stroke. Here, we induced focal IC demyelination in mice by lysophosphatidylcholine (LPC) injection, and examined its effect on motor behavior. We also compared the effect of LPC-induced IC damage to that produced by endothelin-1 (ET1), a potent vasoconstrictor used in experimental stroke lesions. We found that LPC or ET1 injections induced asymmetric motor deficit at 7 days post-lesion (dpl), and that both lesion types displayed increased microglia/macrophage density, myelin loss, and axonal dystrophy. The motor deficit and lesion pathology remained in ET1-injected mice at 28 dpl. In contrast, LPC-injected mice regained motor function by 28 dpl, with corresponding reduction in activated microglia/macrophage density, and recovery of myelin staining and axonal integrity in lesions. These results suggest that LPC-induced IC demyelination results in acute motor deficit and subsequent recovery through remyelination, and may be used to complement future drug screens to identify drugs for promoting remyelination.
Topics: Animals; Axons; Demyelinating Diseases; Endothelin-1; Immunohistochemistry; Internal Capsule; Lysophosphatidylcholines; Macrophages; Male; Mice; Mice, Inbred C57BL; Microglia; Motor Skills Disorders; Myelin Sheath; Oligodendroglia; Recovery of Function; Stroke
PubMed: 32750162
DOI: 10.1111/jnc.15142