Thalamic Connectivity Research Articles

Reconsidering fetal pain

Fetal pain has long been a contentious issue, in large part because fetal pain is often cited as a reason to restrict access to termination of pregnancy or abortion. We...

Preliminary Report on the Effects of a Low Dose of LSD on Resting-State Amygdala Functional Connectivity

BackgroundThe practice of “microdosing,” or the use of repeated, very low doses of lysergic acid diethylamide (LSD) to improve mood or cognition, has received considerable public attention, but empirical studies are lacking. Controlled studies are needed to investigate both the therapeutic potential and the neurobiological underpinnings of this pharmacologic treatment. MethodsThe present study was designed to examine the effects of a single low dose of LSD (13 μg) versus placebo on resting-state functional connectivity and cerebral blood flow in healthy young adults. Twenty men and women, 18 to 35 years old, participated in 2 functional magnetic resonance imaging scanning sessions in which they received placebo or LSD under double-blind conditions. During each session, the participants completed drug effect and mood questionnaires, and physiological measures were recorded. During expected peak drug effect, they underwent resting-state blood oxygen level–dependent and arterial spin labeling scans. Cerebral blood flow as well as amygdala and thalamic connectivity were analyzed. ResultsLSD increased amygdala seed-based connectivity with the right angular gyrus, right middle frontal gyrus, and the cerebellum, and decreased amygdala connectivity with the left and right postcentral gyrus and the superior temporal gyrus. This low dose of LSD had weak and variable effects on mood, but its effects on positive mood were positively correlated with the increase in amygdala–middle frontal gyrus connectivity strength. ConclusionsThese preliminary findings show that a very low dose of LSD, which produces negligible subjective changes, alters brain connectivity in limbic circuits. Additional studies, especially with repeated dosing, will reveal whether these neural changes are related to the drug’s purported antidepressant effect.

P.681 Longitudinal resting state analysis of thalamic connectivity shows improvement in prefrontal connectivity after 12 months in first-episode psychosis

P.681 Longitudinal resting state analysis of thalamic connectivity shows improvement in prefrontal connectivity after 12 months in first-episode psychosis

Resting-state connectivity and the effects of treatment in restless legs syndrome

ObjectivesResting-state brain connectivity has been shown to differ for Restless Legs Syndrome (RLS) compared to healthy control (CON) groups. This study evaluates the degree these RLS-CON differences are changed by concurrent treatment. MethodsResting-state functional MRIs were obtained from 32 idiopathic RLS patients during the morning asymptomatic period and 16 age and gender-matched CON subjects. Of the 32 RLS patients, 16 were drug-naïve (DN-RLS), and 16 were regularly drug-treated using a dopamine agonist (DT-RLS). Various assessments of disease characteristics were also performed. The primary purpose was to assess the replicability of prior results and the effects of treatment on these differences between controls and untreated RLS patients. Resting-state connectivity was analyzed by a seed-based method using the bilateral ventral-posterolateral nuclei (VPLN) in the thalamus. ResultsIn the DN-RLS group, compared to the CON group, three areas (the bilateral lingual gyri and right middle temporal gyrus) were replicated. The three replicated areas did not significantly differ for DT-RLS compared to DN-RLS. DT-RLS compared to DN-RLS had significantly higher thalamic connectivity for the left uvula, right tuber, left anterior insula, and right declive. ConclusionsThalamic connectivity to the bilateral lingual gyri and right middle temporal gyrus is a replicable finding in DN-RLS that was not affected by dopamine agonist treatments. Other changes in thalamic connectivity were altered by dopamine agonist treatment. These treatment effects may be pertinent to the known treatment benefits of a dopamine agonist on RLS symptoms.

Do the Dento-Thalamic Connections of Genetic Absence Epilepsy Rats from Strasbourg Differ from Those of Control Wistar Rats?

The thalamo-cortical circuit is important in the genesis of absence epilepsy. This circuit can be influenced by connecting pathways from various parts of central nervous system. The aim of the present study is to define the dento-thalamic connections in Wistar animals and compare the results with genetic absence epilepsy rats from Strasbourg (GAERS) using the biotinylated dextran amine (BDA) tracer. We injected BDA into the dentate nucleus of 13 (n = 6 Wistar and n = 7 GAERS) animals. The dento-thalamic connections in the Wistar animals were denser and were connected to a wider range of thalamic nuclei compared with GAERS. The dentate nucleus was bilaterally connected to the central (central medial [CM], paracentral [PC]), ventral (ventral medial [VM], ventral lateral [VL], and ventral posterior lateral [VPL]), and posterior (Po) thalamic nuclei in Wistar animals. The majority of these connections were dense contralaterally and scarce ipsilaterally. Contralateral connections were present with the parafascicular (PF), ventral posterior medial, ventral anterior (VA), and central lateral (CL) thalamic nuclei in Wistar animals. Whereas in GAERS, bilateral connections were observed with the VL and CM. Contralateral connections were present with the PC, VM, VA, and PF thalamic nuclei in GAERS. The CL, VPL, and Po thalamic nucleus connections were not observed in GAERS. The present study showed weak/deficit dento-thalamic connections in GAERS compared with control Wistar animals. The scarce information flow from the dentate nucleus to thalamus in GAERS may have a deficient modulatory role on the thalamus and thus may affect modulation of the thalamo-cortical circuit.

Hierarchical organization of cortical and thalamic connectivity.

The mammalian cortex is a laminar structure composed of many areas and cell types densely interconnected in complex ways, for which generalizable principles of organization remain mostly unknown. Here, we present a significant expansion of the Allen Mouse Brain Connectivity Atlas resource1, with ~1,000 new tracer experiments in cortex and its major satellite structure, the thalamus, using Cre driver lines to comprehensively and selectively label brain-wide connections by layer and projection neuron class. We derived a set of generalized anatomical rules describing corticocortical, thalamocortical and corticothalamic projections through observations of axon termination patterns. We built a model to assign connection patterns between areas as either feedforward or feedback, and generated testable predictions of hierarchical positions for individual cortical and thalamic areas and for cortical network modules. Our results reveal cell class-specific connections are organized in a shallow hierarchy within the mouse cortical thalamic network.

Dynamic changes in thalamic connectivity following stress and its association with future depression severity.

IntroductionTracking stress‐induced brain activity and connectivity dynamically and examining activity/connectivity‐associated recovery ability after stress might be an effective way of detecting stress vulnerability.MethodsUsing two widely used stress paradigms, a speech task (social stress) and a mathematical calculation task (mental loading stress), we examined common changes in regional homogeneity (ReHo) and functional connectivity (FC) before, during, and after the two stressful tasks in thirty‐nine college students. A counting breath relaxation task was employed as a contrast task. ReHo and FC were compared between subjects with higher versus lower depression symptoms (assessed by the Beck Depression Inventory, BDI). We developed a recovery index (RI) based on dynamic changes of ReHo/FC to evaluate individuals' ability to recover from a stressful state. To assess RI's usefulness in predicting future depression severity, BDI was also measured at one‐year follow‐up.ResultsOur results revealed a ReHo decrease after both stressful tasks and a ReHo increase after the relaxation task in bilateral thalamus. The ReHo decrease after both stressful tasks was more significant in the higher BDI than the lower BDI group. Higher ReHo RI of the right thalamus in the higher BDI groups was significantly correlated with lower BDI severity at one‐year follow‐up. Bilateral thalamus also showed increased FC with the default mode network and decreased FC with the executive control network after the stressful tasks.ConclusionThese findings highlight the importance of tracking resting activity and connectivity of thalamus dynamically for detecting stress vulnerability.

Early Sensory Loss Alters the Dendritic Branching and Spine Density of Supragranular Pyramidal Neurons in Rodent Primary Sensory Cortices.

Multisensory integration in primary auditory (A1), visual (V1), and somatosensory cortex (S1) is substantially mediated by their direct interconnections and by thalamic inputs across the sensory modalities. We have previously shown in rodents (Mongolian gerbils) that during postnatal development, the anatomical and functional strengths of these crossmodal and also of sensory matched connections are determined by early auditory, somatosensory, and visual experience. Because supragranular layer III pyramidal neurons are major targets of corticocortical and thalamocortical connections, we investigated in this follow-up study how the loss of early sensory experience changes their dendritic morphology. Gerbils were sensory deprived early in development by either bilateral sciatic nerve transection at postnatal day (P) 5, ototoxic inner hair cell damage at P10, or eye enucleation at P10. Sholl and branch order analyses of Golgi-stained layer III pyramidal neurons at P28, which demarcates the end of the sensory critical period in this species, revealed that visual and somatosensory deprivation leads to a general increase of apical and basal dendritic branching in A1, V1, and S1. In contrast, dendritic branching, particularly of apical dendrites, decreased in all three areas following auditory deprivation. Generally, the number of spines, and consequently spine density, along the apical and basal dendrites decreased in both sensory deprived and non-deprived cortical areas. Therefore, we conclude that the loss of early sensory experience induces a refinement of corticocortical crossmodal and other cortical and thalamic connections by pruning of dendritic spines at the end of the critical period. Based on present and previous own results and on findings from the literature, we propose a scenario for multisensory development following early sensory loss.

Basal ganglia and thalamic tract connectivity in very preterm and full-term children; associations with 7-year neurodevelopment.

Altered basal ganglia and thalamic connectivity may be critical for cognitive, motor and behavioural impairments common to very preterm (<32 weeks' gestational age) children. This study aims to (1) compare corticostriatal and thalamocortical tract connectivity between very preterm and term-born children at 7 years of age; (2) explore tract connectivity associations with 7-year neurodevelopmental outcomes, and whether these relationships differed between groups. Eighty-three very preterm and 19 term-born (≥37 weeks' gestational age) children underwent structural and diffusion magnetic resonance imaging and had a neuropsychological assessment at 7 years. Corticostriatal and thalamocortical tracts were reconstructed and white matter connectivity was estimated with apparent fibre density. Compared with term-born controls, very preterm children had decreased connectivity in tracts linking the caudate to right motor areas (-10%, p = 0.03) and the thalamus with left motor areas (-5.7%, p = 0.03). Reduced connectivity in corticostriatal and thalamocortical tracts was associated with adverse motor functioning in both groups (p = 0.06). Decreased connectivity of the left caudate and putamen with the lateral prefrontal cortex was associated with lower reading performance for controls (p = 0.06). Corticostriatal and thalamocortical tracts are vulnerable to very preterm birth. Poorer connectivity in these tracts may underlie the motor impairments observed in very preterm children.

Thalamic Arousal Network Disturbances in Temporal Lobe Epilepsy and Improvement After Surgery

Abstract INTRODUCTION The effects of temporal lobe epilepsy (TLE) on subcortical arousal structures remain incompletely understood. Here we evaluate thalamic arousal network functional connectivity in TLE and examine changes after epilepsy surgery. METHODS We examined 26 adult TLE patients and 26 matched control participants and used resting-state functional magnetic resonance imaging (fMRI) to measure functional connectivity between the thalamus (entire thalamus and 19 bilateral thalamic nuclei) and both neocortex and brainstem ascending reticular activating system (ARAS) nuclei. Postoperative imaging was completed for 19 patients &gt; 1 yr after surgery and compared to preoperative baseline. RESULTS Before surgery, TLE patients demonstrated abnormal thalamo-occipital functional connectivity, losing the normal negative fMRI correlation between the intralaminar central lateral (CL) nucleus and medial occipital lobe seen in controls (P &lt; .001, paired t-test). Patients also had abnormal connectivity between ARAS and CL, lower ipsilateral intrathalamic connectivity, and smaller ipsilateral thalamic volume compared to controls (P &lt; .05 for each, paired t-tests). Abnormal brainstem-thalamic connectivity was associated with impaired visuospatial attention (? = −0.50, P = .02, Spearman's rho), while lower intrathalamic connectivity and volume were related to higher frequency of consciousness-sparing seizures (P &lt; .02, Spearman's rho). After epilepsy surgery, patients with improved seizures showed partial recovery of thalamo-occipital and brainstem-thalamic connectivity, with values more closely resembling controls (P &lt; .01 for each, ANOVA). CONCLUSION Overall, TLE patients demonstrate impaired connectivity in thalamic arousal networks that may be involved in visuospatial attention, but these disturbances may partially recover after successful epilepsy surgery. Thalamic arousal network dysfunction may contribute to morbidity in TLE.

Interstitial Laser Capsulotomy for Refractory Obsessive-Compulsive Disorder-Lesion Size and Energy Deposition Determine Outcome

Abstract INTRODUCTION Current neurosurgical treatment of refractory severe Obsessive Compulsive Disorder either using radiosurgery, deep brain stimulation or lately focused ultrasound results in moderate and/or delayed responses. We describe the first case series in the literature applying high energy interstitial laser ablation (LITT) to successfully treat refractory OCD with immediate and sustained response. METHODS Four patients with OCD underwent bilateral LITT capsulotomy from 2015 to 2019. All patients were reviewed by the Psychiatric Neurosurgery Board of the institution Inclusion criteria were based upon Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score above 30 and inability to function in daily life. Each patient's pre- and postoperative partial and full Y-BOCS scores were collected. The partial Y-BOCS score was assessed 24 h post surgery. Ablation parameters such as total energy delivered, average power, and ablation volume were collected. Extent of connectome disruptions were assessed with volumetric diffusion tensor MRI. RESULTS All patients had YBOCS scores between 31 and 40. Immediate improvement on partial Y-BOCS was noted in all patients 24 h post surgery. (Mean reduction of 83.3 + 20.1%) YBOCS scores after 3 mo went from 35.6 + 3.8 to 17.6 + 4.7, a more than 50% reduction. Lesion volumes were large with an average of 3.13 + 1.1 cc on T2 MRI. Energy deposited ranged from 402.75 to 868.5 Watts (700 C) consistently higher on the right side to create symmetric lesions (P &lt; .01) .Orbito-frontal thalamic connections were reduced by more than 85% on DTI 24 h post surgery and consistently 3 mo postop. CONCLUSION LITT is capable of creating large targeted lesions with real time MR monitoring leading to unprecedented almost immediate and extensive improvement in refractory OCD. Larger lesions due to higher energy deposition resulting in maximum disruption of the hyperactive circuitry underlying OCD are possible with LITT. Also, symptom reduction is superior to alternative techniques.

Community-informed connectomics of the thalamocortical system in generalized epilepsy.

To study the intrinsic organization of the thalamocortical circuitry in patients with generalized epilepsy with tonic-clonic seizures (GTCS) via resting-state fMRI (rs-fMRI) connectome analysis and to evaluate its relation to drug response. In a prospectively followed-up sample of 41 patients and 27 healthy controls, we obtained rs-fMRI and structural MRI. After 1 year of follow-up, 27 patients were classified as seizure-free and 14 as drug-resistant. We examined connectivity within and between resting-state communities in cortical and thalamic subregions. In addition to comparing patients to controls, we examined associations with seizure control. We assessed reproducibility in an independent cohort of 21 patients. Compared to controls, patients showed a more constrained network embedding of the thalamus, while frontocentral neocortical regions expressed increased functional diversity. Findings remained significant after regressing out thalamic volume and cortical thickness, suggesting independence from structural alterations. We observed more marked network imbalances in drug-resistant compared to seizure-free patients. Findings were similar in the reproducibility dataset. Our findings suggest a pathoconnectomic mechanism of generalized epilepsy centered on diverging changes in cortical and thalamic connectivity. More restricted thalamic connectivity could reflect the tendency to engage in recursive thalamocortical loops, which may contribute to hyperexcitability. Conversely, increased connectional diversity of frontocentral networks may relay abnormal activity to an extended bilateral territory. Network imbalances were observed shortly after diagnosis and related to future drug response, suggesting clinical utility.

A-24 Metacognition and behavioral regulation associated with distinct connectivity patterns in autism spectrum disorder

Abstract Objective Executive function (EF) deficits are well documented in children with autism spectrum disorder (ASD)1-2 and are commonly measured clinically using parent ratings3. No studies have investigated whether parent ratings of EF predict brain connectivity in ASD. Aim Examine whether the Behavior Rating Inventory of Executive Function (BRIEF) predicts functional brain connectivity in ASD. Method Resting-state fMRI and behavioral data were obtained from the Autism Brain Imaging Data Exchange (ABIDE-II) database6 (n = 106 ASD, ages 5-13). ROI-to-ROI (Region of Interest) connectivity was computed for 132 ROIs spanning the whole brain, defined using Conn Toolbox. Multiple regression analyses examined the effect of BRIEF metacognition on connectivity while controlling for BRIEF behavioral regulation, and vice versa. Age, sex, and full-scale IQ were included as covariates. FDR correction was used (p &lt; 0.05). Results More severe deficits in metacognition were associated with stronger connectivity between the left hippocampus and several ROIs, including the cerebellum and planum temporale. More severe deficits in metacognition were associated with weaker right hippocampus – right frontal pole connectivity. More severe deficits in behavioral regulation were associated with stronger connectivity between subcortical regions (i.e., thalamus, putamen, and caudate) and regions involved in motor (superior frontal gyrus) and limbic systems (cingulate gyrus). More severe behavioral regulation deficits were associated with weaker cerebellar-cerebellar connectivity. Conclusions Findings suggest that parent-ratings of metacognitive abilities in children with ASD are associated with hippocampal connectivity, while behavioral regulation abilities are associated with thalamic and striatum connections. These results build upon previous studies of metacognition and behavioral regulation 5,6.

Dynamic Neuromagnetic Network Changes of Seizure Termination in Absence Epilepsy: A Magnetoencephalography Study.

Objective: With increasing efforts devoted to investigating the generation and propagation mechanisms of spontaneous spike and wave discharges (SWDs), little attention has been paid to network mechanisms associated with termination patterns of SWDs to date. In the current study, we aimed to identify the frequency-dependent neural network dynamics during the offset of absence seizures.Methods: Fifteen drug-naïve patients with childhood absence epilepsy (CAE) were assessed with a 275-Channel Magnetoencephalography (MEG) system. MEG data were recorded during and between seizures at a sampling rate of 6,000 Hz and analyzed in seven frequency bands. Source localization was performed with accumulated source imaging. Granger causality analysis was used to evaluate effective connectivity networks of the entire brain at the source level.Results: At the low-frequency (1–80 Hz) bands, activities were predominantly distributed in the frontal cortical and parieto–occipito–temporal junction at the offset transition periods. The high-frequency oscillations (HFOs, 80–500 Hz) analysis indicated significant source localization in the medial frontal cortex and deep brain areas (mainly thalamus) during both the termination transition and interictal periods. Furthermore, an enhanced positive cortico–thalamic effective connectivity was observed around the discharge offset at all of the seven analyzed bands, the direction of which was primarily from various cortical regions to the thalamus.Conclusions: Seizure termination is a gradual process that involves both the cortices and the thalamus in CAE. Cortico–thalamic coupling is observed at the termination transition periods, and the cerebral cortex acts as the driving force.

Abnormal Thalamic Functional Connectivity During Light Non–Rapid Eye Movement Sleep in Children With Primary Nocturnal Enuresis

To investigate abnormalities of thalamocortical and intrathalamic functional connectivity (FC) in children with primary nocturnal enuresis (PNE) during light non-rapid eye movement (NREM) sleep using a simultaneous electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) method. Polysomnographic and EEG-fMRI data were obtained during sleep from 61 children with PNE (age 10.2 ± 1.7 years, 59% boys) and 61 age-matched controls (age 10.1 ± 1.4 years, 54% boys). All subjects first participated in one overnight video-polysomnographic study. Total sleep time, percentage of total sleep time in each sleep stage, arousal index, and awakening index were calculated. Simultaneous EEG-fMRI studies were then performed using a 3T MRI system with a 32-channel MRI-compatible EEG system. Visual scoring of EEG data permitted sleep staging. Thalamocortical and intrathalamic FCs in the waking state and at different stages of light sleep were calculated and compared. Children with PNE had a higher percentage of total sleep time in light sleep and a higher arousal index compared with controls. Abnormal thalamocortical FCs were detected in the lateral prefrontal cortex, medial prefrontal cortex, and inferior parietal lobule during light NREM sleep. Abnormal intrathalamic FCs were also detected during light NREM sleep among the motor, occipital, prefrontal, and temporal subdivisions of the thalamus. Abnormal prefrontal and parietal thalamocortical FCs, accompanied by abnormal intrathalamic FCs among the motor, occipital, prefrontal, and temporal subdivision of thalamus during light NREM sleep, may be related to abnormal sleep and enuresis in children with PNE.

Characterization of postsurgical functional connectivity changes in temporal lobe epilepsy.

Seizure outcome after mesial temporal lobe epilepsy (mTLE) surgery is complex and diverse, even across patients with homogeneous presurgical clinical profiles. The authors hypothesized that this is due in part to variations in network connectivity across the brain before and after surgery. Although presurgical network connectivity has been previously characterized in these patients, the objective of this study was to characterize presurgical to postsurgical functional network connectivity changes across the brain after mTLE surgery. Twenty patients with drug-refractory unilateral mTLE (5 left side, 10 female, age 39.3 ± 13.5 years) who underwent either selective amygdalohippocampectomy (n = 13) or temporal lobectomy (n = 7) were included in the study. Presurgical and postsurgical (36.6 ± 14.3 months after surgery) functional connectivity (FC) was measured with 3-T MRI and compared with findings in age-matched healthy controls (n = 44, 21 female, age 39.3 ± 14.3 years). Postsurgical connectivity changes were then related to seizure outcome, type of surgery, and presurgical disease parameters. The results demonstrated significant decreases of FC from control group values across the brain after surgery that were not present before surgery, including many contralateral hippocampal connections distal to the surgical site. Postsurgical impairment of contralateral precuneus to ipsilateral occipital connectivity was associated with seizure recurrence. Presurgical impairment of the contralateral precuneus to contralateral temporal lobe connectivity was associated with those who underwent selective amygdalohippocampectomy compared to those who had temporal lobectomy. Finally, changes in thalamic connectivity after surgery were linearly related to duration of epilepsy and frequency of consciousness-impairing seizures prior to surgery. The widespread contralateral hippocampal FC changes after surgery may be a reflection of an ongoing epileptogenic progression that has been altered by the surgery, rather than a direct result of the surgery itself. This network evolution may contribute to long-term seizure outcome. Therefore, the combination of presurgical network mapping with the understanding of the dynamic effects of surgery on the networks may ultimately be used to create predictors of the likelihood of long-term seizure recurrence in individual patients after mTLE surgery.

Links Between the Amplitude Modulation of Low-Frequency Spontaneous Fluctuation Across Resting State Conditions and Thalamic Functional Connectivity.

A comparison of the different types of resting state reveals some interesting characteristics of spontaneous brain activity that cannot be found in a single condition. Differences in the amplitude of low-frequency fluctuation (ALFF) between the eyes open (EO) and the eyes closed (EC) almost have a spatially distinct pattern with traditional EO-EC activation within sensory systems, suggesting the divergent functional roles of ALFF and activation. However, the underlying mechanism is far from clear. Since the thalamus plays an essential role in sensory processing, one critical step toward understanding the divergences is to depict the relationships between the thalamus and the ALFF modulation in sensory regions. In this preliminary study, we examined the association between the changes of ALFF and the changes of thalamic functional connectivity (FC) between EO and EC. We focused on two visual thalamic nuclei, the lateral geniculate nucleus (LGN) and the pulvinar (Pu). FC results showed that LGN had stronger synchronization with regions in lateral but not in medial visual networks, while Pu had a weaker synchronization with auditory and sensorimotor areas during EO compared with EC. Moreover, the patterns of FC modulation exhibited considerable overlaps with the ALFF modulation, and there were significant correlations between them across subjects. Our findings support the crucial role of the thalamus in amplitude modulation of low-frequency spontaneous activity in sensory systems, and may pave the way to elucidate the mechanisms governing distinction between evoked activation and modulation of low-frequency spontaneous brain activity.

Thalamic arousal network disturbances in temporal lobe epilepsy and improvement after surgery

ObjectiveThe effects of temporal lobe epilepsy (TLE) on subcortical arousal structures remain incompletely understood. Here, we evaluate thalamic arousal network functional connectivity in TLE and examine changes after epilepsy surgery.MethodsWe...

Developmentally divergent sexual dimorphism in the cortico-striatal-thalamic-cortical psychosis risk pathway.

Structural and functional cortico-striatal-thalamic-cortical (CSTC) circuit abnormalities have been observed in schizophrenia and the clinical high-risk state. However, this circuit is sexually dimorphic and changes across neurodevelopment. We examined effects of sex and age on structural and functional properties of the CSTC circuit in a large sample of youth with and without psychosis spectrum symptoms (PSS) from the Philadelphia Neurodevelopmental Cohort. T1-weighted and resting-state functional MRI scans were collected on a 3T Siemens scanner, in addition to participants' cognitive and psychopathology data. After quality control, the total sample (aged 11-21) was n = 1095 (males = 485, females = 610). Structural subdivisions of the striatum and thalamus were identified using the MAGeT Brain segmentation tool. Functional seeds were segmented based on brain network connectivity. Interaction effects among PSS group, sex, and age on striatum, thalamus, and subdivision volumes were examined. A similar model was used to test effects on functional connectivity of the CSTCcircuit. A sex by PSS group interaction was identified, whereby PSS males had higher volumes and PSS females had lower volumes in striatal and thalamic subdivisions. Reduced functional striato-cortical connectivity was found in PSS youth, primarily driven by males, whereby younger male PSS youth also exhibited thalamo-cortical hypo-connectivity (compared to non-PSS youth), vs. striato-cortical hyper-connectivity in older male PSS youth (compared to non-PSS youth). Youth with PSS demonstrate sex and age-dependent differences in striatal and thalamic subdivision structure and functional connectivity. Further efforts at biomarker discovery and early therapeutic intervention targeting the CSTCcircuit in psychosis should consider effects of sex and age.

Deep brain stimulation: Connectivity profile for bradykinesia alleviation.

Subthalamic deep brain stimulation may alleviate bradykinesia in Parkinson patients. Research suggests that this stimulation effect may be mediated by brain networks like the corticocerebellar loop. This study investigated the connectivity between stimulation sites and cortical and subcortical structures to identify connections for effective stimulation. We retrospectively investigated 21 patients with Parkinson disease with bilateral subthalamic deep brain stimulation. Stimulation effectiveness in reducing bradykinesia, tremor, and rigidity was evaluated for each electrode contact in brain hemispheres contralateral to the affected hemibody. Dysarthric side effects were also examined. Probabilistic tractography based on diffusion-weighted imaging was performed in individual patient-specific brains using electrode contacts as seeds. Connectivity profiles of contacts with effective and noneffective stimulation were compared. Connectivity profiles of effective and noneffective contacts differed. Moreover, the connectivity profile for bradykinesia differed from that for rigidity, tremor, or dysarthria. Regarding bradykinesia, effective contacts were significantly more often connected with the ipsilateral superior cerebellar peduncle and the ipsilateral dentate nucleus, which correspond to the ipsilateral portion of the cerebellothalamocortical pathway. Rigidity was mitigated by stimulation of ascending brainstem and intralaminar thalamic connections. Tremor alleviation was related to connections with the internal capsule (anterior limb) and the pallidum. Dysarthric side effects were associated with connections to the supplementary motor area and the decussating cerebellothalamocortical pathway. Whereas bradykinesia seems to be mitigated by stimulation of the ascending, ipsilateral cerebellothalamocortical pathway, stimulation of the descending corticopontocerebellar pathway may be ineffective. Rigidity, tremor, and dysarthric side effects seem to be influenced by different neural networks. ANN NEUROL 2019;85:852-864.