Quantitative susceptibility mapping in amyotrophic lateral sclerosis: automatic quantification of the magnetic susceptibility in the subcortical nuclei.

Objective: Previous studies have suggested a link between dysregulation of cortical iron levels and neuronal loss in amyotrophic lateral sclerosis (ALS) patients. However, few studies have reported differences in quantitative susceptibility mapping (QSM) values in subcortical nuclei between patients with ALS and healthy controls (HCs). Methods: MRI was performed using a 3 Tesla Prisma scanner (64-channel head coil), including 3D T1-MPRAGE and multi-echo 3D GRE for QSM reconstruction. Automated QSM segmentation was used to measure susceptibility values in the subcortical nuclei, which were compared between the groups. Correlations with clinical scales were analyzed. Group comparisons were performed using independent t-tests, with p < 0.05 considered significant. Correlations were assessed using Pearson's correlation, with p < 0.05 considered significant. Cohen's d was reported to compare the standardized mean difference (SMD) of QSM. Results: Twelve patients with limb-onset ALS (mean age 48.7 years, 75% male) and 13 age-, sex-, and handedness-matched HCs (mean age 44.6 years, 69% male) were included. Compared to HCs, ALS patients demonstrated significantly lower susceptibility in the left caudate nucleus (CN) (SMD = -0.845), right CN (SMD = -0.851), whole CN (SMD = -1.016), and left subthalamic nucleus (STN) (SMD = -1.000). Susceptibility in the left putamen (SMD = -0.857), left thalamus (SMD = -1.081), and whole thalamus (SMD = -0.968) was significantly higher in the patients. The susceptibility of the substantia nigra (SN), CN, and pulvinar was positively correlated with disease duration. Conclusions: QSM detects abnormal iron accumulation patterns in the subcortical gray matter of ALS patients, which correlates with disease characteristics, supporting its potential as a neuroimaging biomarker.

Understanding copy number variations through their genes: a molecular view on 16p11.2 deletion and duplication syndromes.

Neurodevelopmental disorders (NDDs) include a broad spectrum of pathological conditions that affect >4% of children worldwide, share common features and present a variegated genetic origin. They include clinically defined diseases, such as autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD), motor disorders such as Tics and Tourette's syndromes, but also much more heterogeneous conditions like intellectual disability (ID) and epilepsy. Schizophrenia (SCZ) has also recently been proposed to belong to NDDs. Relatively common causes of NDDs are copy number variations (CNVs), characterised by the gain or the loss of a portion of a chromosome. In this review, we focus on deletions and duplications at the 16p11.2 chromosomal region, associated with NDDs, ID, ASD but also epilepsy and SCZ. Some of the core phenotypes presented by human carriers could be recapitulated in animal and cellular models, which also highlighted prominent neurophysiological and signalling alterations underpinning 16p11.2 CNVs-associated phenotypes. In this review, we also provide an overview of the genes within the 16p11.2 locus, including those with partially known or unknown function as well as non-coding RNAs. A particularly interesting interplay was observed between MVP and MAPK3 in modulating some of the pathological phenotypes associated with the 16p11.2 deletion. Elucidating their role in intracellular signalling and their functional links will be a key step to devise novel therapeutic strategies for 16p11.2 CNVs-related syndromes.

Navigating Visual Challenges: How Parkinson's Disease Alters Cognitive Priorities in Visual Search.

OBJECTIVE: Parkinson's disease (PD) hampers visual search tasks such as reading, driving, and navigation. We examined expectations from past experiences, guiding cognition and contextual priors, on visual search in PD. METHODS: We compared eye movements as PD and healthy participants searched for a hidden object (target) in cluttered real-world scenes. RESULTS: PD participants prolonged fixation on high-probability (high-prior) locations for the target, consistent across expected and unexpected scenario. Such emphasis on contextual visual priors, evidenced by high fixation duration on high-probability areas, was beneficial when the target was at the expected location but presented challenges when the target was situated in an unlikely place. CONCLUSION: This study contributes to understanding how PD impacts visual search behavior and cognitive processing. The findings indicate that PD alters attention allocation and visual processing by affecting the utilization of contextual visual priors. It provides insights for potential interventions targeting visuo-cognitive deficits in PD patients. Published 2024. This article is a U.S. Government work and is in the public domain in the USA.

Ferroptosis inhibitor ferrostatin-1 attenuates morphine tolerance development in male rats by inhibiting dorsal root ganglion neuronal ferroptosis.

Background: Ferrostatin-1 and liproxstatin-1, both ferroptosis inhibitors, protect cells. Liproxstatin-1 decreases morphine tolerance. Yet, ferrostatin-1's effect on morphine tolerance remains unexplored. This study aimed to evaluate the influence of ferrostatin-1 on the advancement of morphine tolerance and understand the underlying mechanisms in male rats. Methods: This experiment involved 36 adult male Wistar albino rats with an average weight ranging from 220 to 260 g. These rats were categorized into six groups: Control, single dose ferrostatin-1, single dose morphine, single dose ferrostatin-1 + morphine, morphine tolerance (twice daily for five days), and ferrostatin-1 + morphine tolerance (twice daily for five days). The antinociceptive action was evaluated using both the hot plate and tail-flick tests. After completing the analgesic tests, tissue samples were gathered from the dorsal root ganglia (DRG) for subsequent analysis. The levels of glutathione, glutathione peroxidase 4 (GPX4), and nuclear factor erythroid 2-related factor 2 (Nrf2), along with the measurements of total oxidant status (TOS) and total antioxidant status (TAS), were assessed in the tissues of the DRG. Results: After tolerance development, the administration of ferrostatin-1 resulted in a significant decrease in morphine tolerance (P < 0.001). Additionally, ferrostatin-1 treatment led to elevated levels of glutathione, GPX4, Nrf2, and TOS (P < 0.001), while simultaneously causing a decrease in TAS levels (P < 0.001). Conclusions: The study found that ferrostatin-1 can reduce morphine tolerance by suppressing ferroptosis and reducing oxidative stress in DRG neurons, suggesting it as a potential therapy for preventing morphine tolerance.

TRPV1 and mast cell involvement in repeated variate stress (RVS) induced urinary bladder dysfunction in adult female mice.

The etiology of interstitial cystitis/bladder pain syndrome (IC/BPS) is unknown but likely multifactorial. IC/BPS symptoms can be exacerbated by psychological stress, but underlying mechanisms remain to be defined. TRPV1 channels, expressed on nerve fibers, have been implicated in bladder dysfunction and colonic hypersensitivity with stress in rodents. Histamine/H1R activation of TRPV1+ nerves increases bladder afferent fiber sensitivity to distension. TRPV1 channels are also expressed on mast cells, previously implicated in contributing to IC/BPS etiology and symptoms. We have examined the contribution of TRPV1 and mast cells to bladder dysfunction after repeated variate stress (RVS). RVS increased (p ≤ 0.05) serum and fecal corticosterone expression and induced anxiety-like behavior in wild type (WT) mice. Intravesical instillation of the selective TRPV1 antagonist capsazepine (CPZ) rescued RVS-induced bladder dysfunction in WT mice. Trpv1 knockout (KO) mice did not increase voiding frequency with RVS and did not exhibit increased serum corticosterone expression despite exhibiting anxiety-like behavior. Mast cell deficient mice (B6.Cg-Kitw-sh) failed to demonstrate RVS-induced increased voiding frequency or serum corticosterone expression whereas control (no stress) mast cell deficient mice had similar functional bladder capacity to WT mice. TRPV1 protein expression was significantly increased in the rostral lumbar (L1-L2) spinal cord and dorsal root ganglia in WT mice exposed to RVS but no changes were observed in lumbosacral (L6-S1) spinal segments or DRG. These studies demonstrated TRPV1 and mast cell involvement in RVS-induced increased voiding frequency and suggest that TRPV1 and mast cells may be useful targets to mitigate stress-induced urinary bladder dysfunction.

The antisaccadic paradigm: A complementary neuropsychological tool in basal ganglia disorders.

This review explores the role of the antisaccadic task in understanding inhibitory mechanisms in basal ganglia disorders. It conducts a comparative analysis of saccadic profiles in conditions such as Parkinson's disease, Tourette syndrome, obsessive-compulsive disorder, Huntington's disease, and dystonia, revealing distinct patterns and proposing mechanisms for impaired performance. The primary focus is on two inhibitory mechanisms: global, pre-emptive inhibition responsible for suppressing prepotent responses, and slower, selective response inhibition. The antisaccadic task demonstrates practicality in clinical applications, aiding in differential diagnoses, treatment monitoring and reflecting gait control. To further enhance its differential diagnostic value, future directions should address issues such as the standardization of eye-tracking protocol and the integration of eye-tracking data with other disease indicators in a comprehensive dataset.

Cortico-basal ganglia plasticity in motor learning.

One key function of the brain is to control our body's movements, allowing us to interact with the world around us. Yet, many motor behaviors are not innate but require learning through repeated practice. Among the brain's motor regions, the cortico-basal ganglia circuit is particularly crucial for acquiring and executing motor skills, and neuronal activity in these regions is directly linked to movement parameters. Cell-type-specific adaptations of activity patterns and synaptic connectivity support the learning of new motor skills. Functionally, neuronal activity sequences become structured and associated with learned movements. On the synaptic level, specific connections become potentiated during learning through mechanisms such as long-term synaptic plasticity and dendritic spine dynamics, which are thought to mediate functional circuit plasticity. These synaptic and circuit adaptations within the cortico-basal ganglia circuitry are thus critical for motor skill acquisition, and disruptions in this plasticity can contribute to movement disorders.

D2 dopamine receptor expression, reactivity to rewards, and reinforcement learning in a complex value-based decision-making task.

Different dopamine subtypes have opposing dynamics at post-synaptic receptors, with the ratio of D1 to D2 receptors determining the relative sensitivity to gains and losses, respectively, during value-based learning. This effective sensitivity to different reward feedback interacts with phasic dopamine levels to determine the effectiveness of learning, particularly in dynamic feedback situations where frequency and magnitude of rewards need to be integrated over time to make optimal decisions. We modeled this effect in simulations of the underlying basal ganglia pathways and then tested the predictions in individuals with a variant of the human dopamine receptor D2 (DRD2; -141C Ins/Del and Del/Del) gene that associates with lower levels of D2 receptor expression (N=119) and compared their performance in the Iowa Gambling Task (IGT) to non-carrier controls (N=319). Ventral striatal (VS) reactivity to rewards was measured in the Cards task with fMRI. DRD2 variant carriers made less effective decisions than non-carriers, but this effect was not moderated by VS reward reactivity as is hypothesized by our model. These results suggest that the interaction between dopamine receptor subtypes and reactivity to rewards during learning may be more complex than originally thought.

Dyskinetic Cerebral Palsy in Children: Clinical Perspectives on Common Comorbidities and Health-Related Quality of Life.

BACKGROUND: The data on specific comorbidities in children with dyskinetic cerebral palsy (DCP) is limited. We evaluated the pattern of comorbidities and health related quality of life (HRQOL) in these children and compared them between etiological and motor impairment subgroups. METHODOLOGY: This cross-sectional study was conducted over 18 months in children with DCP of both sex, and age between one and 14 years. Comorbidities were assessed using standardized scales such as gross motor functioning scale (GMFCS), developmental profile-3 (DP-3), developmental behaviour checklist, sleep behaviour questionnaire (SBQ), and caregiver questionnaire. RESULTS: Sixty-five children with DCP were evaluated (hyperbilirubinemia n = 43, 66% and perinatal asphyxia n = 19, 29%). The majority of children were severely affected in gross motor functioning (level IV 29.2% and level V 53.8%). Epilepsy was seen in 21.5% of cases (19% in hyperbilirubinemia and 32% in asphyxia, p = 0.4). The mean age of onset of seizures was 15.4 + 20.6 months (range 2-72). Visual problems were seen in 54% of cases and included upgaze palsy, squint, refractive error, optic atrophy and cortical blindness. A significant proportion of children with hyperbilirubinemia had upgaze palsy as compared to those with perinatal asphyxia (70% vs. 32%, p 0.01). Rest of the visual problems were not significantly different between the two etiological subgroups. Drooling (87.6%), protein-energy malnutrition (66.6%), and reflux (57%) were the most common gastrointestinal problems in children with DCP. Children with DCP showed problems in social relating (33.8%), anxiety (26.2%), and self-absorbed behaviour (7.7%). However, there were no statistically significant differences between the etiological, motor impairment and age-based subgroups. Children with DCP had high scores on SBQ, suggesting sleep problems. Sleep scores were similar in the hyperbilirubinemia and perinatal asphyxia subgroups. Greater sleep problems were noted in children aged < 4y (70.6 + 10.1 vs. 56.5 + 11.3, p < 0.05 as compared to children above 4y of age) and severe motor impairments (68.2 + 11.3 vs. 57.2 + 13.1, p 0.008 as compared to mild-moderate motor impairment). Poor overall developmental scores were seen in 61.5% children and were significantly associated with GMFCS (p 0.04). The majority of children showed impairments in physical (58.5%), adaptive behaviour (58.5%), social-emotional (50.8%), cognitive (60%) and communication (52%) subscales of DP-3. Cognitive impairment was similar in the etiological (hyperbilirubinemia vs. perinatal asphyxia, p = 0.3), and motor impairment (mild-moderate vs. severe, p = 0.9) subgroups. HRQOL was significantly affected by motor impairment in positioning-transfer (p value 0.0001), and interaction-communication domains (p value 0.0001), however, there was no difference based on the etiology of hyperbilirubinemia and asphyxia. CONCLUSION: Children with DCP demonstrate several comorbidities and impaired quality of life. These are similar in hyperbilirubinemia and perinatal asphyxia cohorts, expect for significant proportion of upgaze palsy in DCP secondary to hyperbilirubinemia. Younger children have more problematic behaviour and impaired sleep quality. Severe motor disability influences the developmental outcomes, cognition, sleep and HRQOL in children with DCP.

GRT-X Stimulates Dorsal Root Ganglia Axonal Growth in Culture via TSPO and Kv7.2/3 Potassium Channel Activation.

GRT-X, which targets both the mitochondrial translocator protein (TSPO) and the Kv7.2/3 (KCNQ2/3) potassium channels, has been shown to efficiently promote recovery from cervical spine injury. In the present work, we investigate the role of GRT-X and its two targets in the axonal growth of dorsal root ganglion (DRG) neurons. Neurite outgrowth was quantified in DRG explant cultures prepared from wild-type C57BL6/J and TSPO-KO mice. TSPO was pharmacologically targeted with the agonist XBD173 and the Kv7 channels with the activator ICA-27243 and the inhibitor XE991. GRT-X efficiently stimulated DRG axonal growth at 4 and 8 days after its single administration. XBD173 also promoted axonal elongation, but only after 8 days and its repeated administration. In contrast, both ICA27243 and XE991 tended to decrease axonal elongation. In dissociated DRG neuron/Schwann cell co-cultures, GRT-X upregulated the expression of genes associated with axonal growth and myelination. In the TSPO-KO DRG cultures, the stimulatory effect of GRT-X on axonal growth was completely lost. However, GRT-X and XBD173 activated neuronal and Schwann cell gene expression after TSPO knockout, indicating the presence of additional targets warranting further investigation. These findings uncover a key role of the dual mode of action of GRT-X in the axonal elongation of DRG neurons.

Communicating pain: emerging axonal signaling in peripheral neuropathic pain.

Peripheral nerve damage often leads to the onset of neuropathic pain (NeuP). This condition afflicts millions of people, significantly burdening healthcare systems and putting strain on families' financial well-being. Here, we will focus on the role of peripheral sensory neurons, specifically the Dorsal Root Ganglia neurons (DRG neurons) in the development of NeuP. After axotomy, DRG neurons activate regenerative signals of axons-soma communication to promote a gene program that activates an axonal branching and elongation processes. The results of a neuronal morphological cytoskeleton change are not always associated with functional recovery. Moreover, any axonal miss-targeting may contribute to NeuP development. In this review, we will explore the epidemiology of NeuP and its molecular causes at the level of the peripheral nervous system and the target organs, with major focus on the neuronal cross-talk between intrinsic and extrinsic factors. Specifically, we will describe how failures in the neuronal regenerative program can exacerbate NeuP.

The parasympathetic and sensory innervation of the proximal and distal colon in male mice.

Introduction: The distributions of extrinsic neurons innervating the colon show differences in experimental animals from humans, including the vagal and spinal parasympathetic innervation to the distal colon. The neuroanatomical tracing to the mouse proximal colon has not been studied in details. This study aimed to trace the locations of extrinsic neurons projecting to the mouse proximal colon compared to the distal colon using dual retrograde tracing. Methods: The parasympathetic and sensory neurons projecting to colon were assessed using Cholera Toxin subunit B conjugated to Alexa-Fluor 488 or 555 injected in the proximal and distal colon of the same mice. Results: Retrograde tracing from the proximal and distal colon labeled neurons in the dorsal motor nucleus of the vagus (DMV) and the nodose ganglia, while the tracing from the distal colon did not label the parasympathetic neurons in the lumbosacral spinal cord at L6-S1. Neurons in the pelvic ganglia which were cholinergic projected to the distal colon. There were more neurons in the DMV and nodose ganglia projecting to the proximal than distal colon. The right nodose ganglion had a higher number of neurons than the left ganglion innervating the proximal colon. In the dorsal root ganglia (DRG), the highest number of neurons traced from the distal colon were at L6, and those from the proximal colon at T12. DRG neurons projected closely to the cholinergic neurons in the intermediolateral column of L6 spinal cord. Small percentages of neurons with dual projections to both the proximal and distal colon existed in the DMV, nodose ganglia and DRG. We also observed long projecting neurons traced from the caudal distal colon to the transverse and proximal colon, some of which were calbindin immunoreactive, while there were no retrogradely labeled neurons traced from the proximal to distal colon. Discussion: These data demonstrated that the vagal motor and motor and sensory neurons innervate both the proximal and distal colon in mice, and the autonomic neurons in the intermediate zone of the lumbosacral spinal cord do not project directly to the mouse colon, which differs from that in humans.

Sex differences in the distribution and density of regulatory interneurons in the striatum.

Introduction: Dysfunction of the cortico-basal circuitry - including its primary input nucleus, the striatum - contributes to neuropsychiatric disorders, such as autism and Tourette Syndrome (TS). These conditions show marked sex differences, occurring more often in males than in females. Regulatory interneurons, such as cholinergic interneurons (CINs) and parvalbumin-expressing GABAergic fast spiking interneurons (FSIs), are implicated in human neuropsychiatric disorders such as TS, and ablation of these interneurons produces relevant behavioral pathology in male mice, but not in females. Here we investigate sex differences in the density and distribution of striatal interneurons. Methods: We use stereological quantification of CINs, FSIs, and somatostatin-expressing (SOM) GABAergic interneurons in the dorsal striatum (caudate-putamen) and the ventral striatum (nucleus accumbens) in male and female mice. Results: Males have a higher density of CINs than females, especially in the dorsal striatum; females have equal distribution between dorsal and ventral striatum. FSIs showed similar distributions, with a greater dorsal-ventral density gradient in males than in females. SOM interneurons were denser in the ventral than in the dorsal striatum, with no sex differences. Discussion: These sex differences in the density and distribution of FSIs and CINs may contribute to sex differences in basal ganglia function, particularly in the context of psychopathology.

Derivation of two iPSC lines (KAIMRCi004-A, KAIMRCi004-B) from a Saudi patient with Biotin-Thiamine-responsive Basal Ganglia Disease (BTBGD) carrying homozygous pathogenic missense variant in the SCL19A3 gene.

The neurometabolic disorder known as biotin-thiamine-responsive basal ganglia disease (BTBGD) is a rare autosomal recessive condition linked to bi-allelic pathogenic mutations in the SLC19A3 gene. BTBGD is characterized by progressive encephalopathy, confusion, seizures, dysarthria, dystonia, and severe disabilities. Diagnosis is difficult due to the disease's rare nature and diverse clinical characteristics. The primary treatment for BTBGD at this time is thiamine and biotin supplementation, while its long-term effectiveness is still being investigated. In this study, we have generated two clones of induced pluripotent stem cells (iPSCs) from a 10-year-old female BTBGD patient carrying a homozygous mutation for the pathogenic variant in exon 5 of the SLC19A3 gene, c.1264A > G (p.Thr422Ala). We have confirmed the pluripotency of the generated iPS lines and successfully differentiated them to neural progenitors. Because our understanding of genotype-phenotype correlations in BTBGD is limited, the establishment of BTBGD-iPSC lines with a homozygous SLC19A3 mutation provides a valuable cellular model to explore the molecular mechanisms underlying SLC19A3-associated cellular dysfunction. This model holds potential for advancing the development of novel therapeutic strategies.

Detecting rhythmic spiking through the power spectra of point process model residuals.

Objective.Oscillations figure prominently as neurological disease hallmarks and neuromodulation targets. To detect oscillations in a neuron's spiking, one might attempt to seek peaks in the spike train's power spectral density (PSD) which exceed a flat baseline. Yet for a non-oscillating neuron, the PSD is not flat: The recovery period ("RP", the post-spike drop in spike probability, starting with the refractory period) introduces global spectral distortion. An established "shuffling" procedure corrects for RP distortion by removing the spectral component explained by the inter-spike interval (ISI) distribution. However, this procedure sacrifices oscillation-related information present in the ISIs, and therefore in the PSD. We asked whether point process models (PPMs) might achieve more selective RP distortion removal, thereby enabling improved oscillation detection.Approach.In a novel "residuals" method, we first estimate the RP duration (nr) from the ISI distribution. We then fit the spike train with a PPM that predicts spike likelihood based on the time elapsed since the most recent of any spikes falling within the preceding nrmilliseconds. Finally, we compute the PSD of the model's residuals.Main results.We compared the residuals and shuffling methods' ability to enable accurate oscillation detection with flat baseline-assuming tests. Over synthetic data, the residuals method generally outperformed the shuffling method in classification of true- versus false-positive oscillatory power, principally due to enhanced sensitivity in sparse spike trains. In single-unit data from the internal globus pallidus (GPi) and ventrolateral anterior thalamus (VLa) of a parkinsonian monkey -- in which alpha-beta oscillations (8-30 Hz) were anticipated -- the residuals method reported the greatest incidence of significant alpha-beta power, with low firing rates predicting residuals-selective oscillation detection.Significance.These results encourage continued development of the residuals approach, to support more accurate oscillation detection. Improved identification of oscillations could promote improved disease models and therapeutic technologies.

Tlx3 mediates neuronal differentiation and proper condensation of the developing trigeminal ganglion.

The trigeminal ganglion, the largest of the vertebrate cranial ganglia, is comprised of sensory neurons that relay sensations of pain, touch, and temperature to the brain. These neurons are derived from two embryonic cell types, the neural crest and ectodermal placodes, whose interactions are critical for proper ganglion formation. While the T-cell leukemia homeobox 3 (Tlx3) gene is known to be expressed in placodally-derived sensory neurons and necessary for their differentiation, little was known about Tlx3 expression and/or function in the neural crest-derived component of the developing trigeminal ganglion. By combining lineage labeling with in situ hybridization in the chick embryo, we show that neural crest-derived cells that contribute to the cranial trigeminal ganglion express Tlx3 at a time point that coincides with the onset of ganglion condensation. Importantly, loss of Tlx3 function in vivo diminishes the overall size and abundance of neurons within the trigeminal ganglion. Conversely, ectopic expression of Tlx3 in migrating cranial neural crest results in their premature neuronal differentiation. Taken together, our results demonstrate a critical role for Tlx3 in neural crest-derived cells during chick trigeminal gangliogenesis.

Complete persistence of the primary somatosensory system in zebrafish.

The somatosensory system detects peripheral stimuli that are translated into behaviors necessary for survival. Fishes and amphibians possess two somatosensory systems in the trunk: the primary somatosensory system, formed by the Rohon-Beard neurons, and the secondary somatosensory system, formed by the neural crest cell-derived neurons of the Dorsal Root Ganglia. Rohon-Beard neurons have been characterized as a transient population that mostly disappears during the first days of life and is functionally replaced by the Dorsal Root Ganglia. Here, I follow Rohon-Beard neurons in vivo and show that the entire repertoire remains present in zebrafish from 1-day post-fertilization until the juvenile stage, 15-days post-fertilization. These data indicate that zebrafish retain two complete somatosensory systems until at least a developmental stage when the animals display complex behavioral repertoires.

Quantitative susceptibility mapping based basal ganglia segmentation via AGSeg: leveraging active gradient guiding mechanism in deep learning.

Background: With better visual contrast and the ability for magnetic susceptibility quantification analysis, quantitative susceptibility mapping (QSM) has emerged as an important magnetic resonance imaging (MRI) method for basal ganglia studies. Precise segmentation of basal ganglia is a prerequisite for quantification analysis of tissue magnetic susceptibility, which is crucial for subsequent disease diagnosis and surgical planning. The conventional method of localizing and segmenting basal ganglia heavily relies on layer-by-layer manual annotation by experts, resulting in a tedious amount of workload. Although several morphology registration and deep learning based methods have been developed to automate segmentation, the voxels around the nuclei boundary remain a challenge to distinguish due to insufficient tissue contrast. This paper proposes AGSeg, an active gradient guidance-based susceptibility and magnitude information complete (MIC) network for real-time and accurate basal ganglia segmentation. Methods: Various datasets, including clinical scans and data from healthy volunteers, were collected across multiple centers with different magnetic field strengths (3T/5T/7T), with a total of 210 three-dimensional (3D) susceptibility measurements. Manual segmentations following fixed rules for anatomical borders annotated by experts were used as ground truth labels. The proposed network took QSM maps and Magnitude images as two individual inputs, of which the features are selectively enhanced in the proposed magnitude information complete (MIC) module. AGSeg utilized a dual-branch architecture, with Seg-branch aiming to generate a proper segmentation map and Grad-branch to reconstruct the gradient map of regions of interest (ROIs). With the support of the newly designed active gradient module (AGM) and gradient guiding module (GGM), the Grad-branch provided attention guidance for the Seg-branch, facilitating it to focus on the boundary of target nuclei. Results: Ablation studies were conducted to assess the functionality of the proposed modules. Significant performance decrement was observed after ablating relative modules. AGSeg was evaluated against several existing methods on both healthy and clinical data, achieving an average Dice similarity coefficient (DSC) =0.874 and average 95% Hausdorff distance (HD95) =2.009. Comparison experiments indicated that our model had superior performance on basal ganglia segmentation and better generalization ability over existing methods. The AGSeg outperformed all implemented comparison deep learning algorithms with average DSC enhancement ranging from 0.036 to 0.074. Conclusions: The current work integrates a deep learning-based method into automated basal ganglia segmentation. The high processing speed and segmentation robustness of AGSeg contribute to the feasibility of future surgery planning and intraoperative navigation. Experiments show that leveraging active gradient guidance mechanisms and magnitude information completion can facilitate the segmentation process. Moreover, this approach also offers a portable solution for other multi-modality medical image segmentation tasks.

Subcortical Brain Volumes and Neurocognitive Function in Children With Perinatal HIV Exposure: A Population-Based Cohort Study in South Africa.

Background: Children who are HIV-exposed and uninfected (HEU) are at risk for early neurodevelopmental impairment. Smaller basal ganglia nuclei have been reported in neonates who are HEU compared to HIV-unexposed (HU); however, neuroimaging studies outside infancy are scarce. We examined subcortical brain structures and associations with neurocognition in children who are HEU. Methods: This neuroimaging study was nested within the Drakenstein Child Health Study birth cohort in South Africa. We compared (T1-weighted) magnetic resonance imaging-derived subcortical brain volumes between children who were HEU (n = 70) and HU (n = 92) at age 2-3 years using linear regression. Brain volumes were correlated with neurodevelopmental outcomes measured with the Bayley Scales of Infant and Toddler Development III. Results: Compared to HU children, on average children who were HEU had 3% lower subcortical grey matter volumes. Analyses of individual structures found smaller volume of the putamen nucleus in the basal ganglia (-5% difference, P = .016) and the hippocampus (-3% difference, P = .044), which held on adjustment for potential confounders (P < .05). Maternal viremia and lower CD4 count in pregnancy were associated with smaller child putamen volumes. Children who were HEU had lower language scores than HU; putamen and hippocampus volumes were positively correlated with language outcomes. Conclusions: Overall, children who are HEU had a pattern of smaller subcortical volumes in the basal ganglia and hippocampal regions compared to HU children, which correlated with language function. Findings suggest that optimizing maternal perinatal HIV care is important for child brain development. Further studies are needed to investigate underlying mechanisms and long-term outcomes.