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Neuropsychopharmacology : Official... Mar 2024Thalamic abnormalities have been repeatedly implicated in the pathophysiology of schizophrenia and other neurodevelopmental disorders. Uncovering the etiology of...
Thalamic abnormalities have been repeatedly implicated in the pathophysiology of schizophrenia and other neurodevelopmental disorders. Uncovering the etiology of thalamic abnormalities and how they may contribute to illness phenotypes faces at least two obstacles. First, the typical developmental trajectories of thalamic nuclei and their association with cognition across the lifespan are largely unknown. Second, modest effect sizes indicate marked individual differences and pose a significant challenge to personalized medicine. To address these knowledge gaps, we characterized the development of thalamic nuclei volumes using normative models generated from the Human Connectome Project Lifespan datasets (5-100+ years), then applied them to an independent clinical cohort to determine the frequency of thalamic volume deviations in people with schizophrenia (17-61 years). Normative models revealed diverse non-linear age effects across the lifespan. Association nuclei exhibited negative age effects during youth but stabilized in adulthood until turning negative again with older age. Sensorimotor nuclei volumes remained relatively stable through youth and adulthood until also turning negative with older age. Up to 18% of individuals with schizophrenia exhibited abnormally small (i.e., below the 5th centile) mediodorsal and pulvinar volumes, and the degree of deviation, but not raw volumes, correlated with the severity of cognitive impairment. While case-control differences are robust, only a minority of patients demonstrate unusually small thalamic nuclei volumes. Normative modeling enables the identification of these individuals, which is a necessary step toward precision medicine.
PubMed: 38480909
DOI: 10.1038/s41386-024-01837-y -
International Orthopaedics Jun 2024To assess the efficacy of arthroscopic debridement and reduction through two medial portals for the treatment of developmental dislocation of the hip (DDH) with failure...
PURPOSE
To assess the efficacy of arthroscopic debridement and reduction through two medial portals for the treatment of developmental dislocation of the hip (DDH) with failure of initial closed reduction and to explore key pathological structures obstructing reduction.
METHODS
Forty-eight children with 58 irreducible dislocated hips treated by arthroscopic reduction between January 2017 and December 2020 were retrospectively evaluated. Arthroscopic reduction was performed via two medial portals located in the superior and inferior adductor longus. All intra-articular obstacles were eliminated via arthroscopy, followed by manual reduction and spica cast immobilization. The surgical duration, extent of improvement in the safe zone, and extent of secondary surgical treatment were noted. All the children were followed up for > 24 months. Hip function and radiographic outcomes were evaluated.
RESULTS
All 58 hips showed safe zone improvement and concentric reduction after arthroscopic debridement. Hypertrophic ligamentum teres and thickened pulvinars were detected and resected in all hips. Constrictive capsules preventing reduction were observed in 15 hips, which needed to be further released. No inverted labrum was observed. Secondary surgery was performed in four hips with redislocation and seven hips with subluxation during follow-up. The remaining 47 hips (81.03%) maintained their reduction at the last follow-up. Excellent and good clinical outcomes were achieved in 95.74% of patients according to McKay's criteria. Two hips, three hips, and one hip were diagnosed with grade I, II, and III osteonecrosis of the femoral head, respectively.
CONCLUSION
This study demonstrated that arthroscopic debridement and reduction is a safe and feasible choice for treating irreducible DDH.
Topics: Humans; Arthroscopy; Male; Debridement; Female; Retrospective Studies; Child, Preschool; Treatment Outcome; Hip Dislocation, Congenital; Infant; Treatment Failure; Developmental Dysplasia of the Hip; Child
PubMed: 38478021
DOI: 10.1007/s00264-024-06140-5 -
European Journal of Neurology Jun 2024Thalamic alterations have been reported as a major feature in presymptomatic and symptomatic patients carrying the C9orf72 mutation across the frontotemporal...
BACKGROUND AND PURPOSE
Thalamic alterations have been reported as a major feature in presymptomatic and symptomatic patients carrying the C9orf72 mutation across the frontotemporal dementia-amyotrophic lateral sclerosis (ALS) spectrum. Specifically, the pulvinar, a high-order thalamic nucleus and timekeeper for large-scale cortical networks, has been hypothesized to be involved in C9orf72-related neurodegenerative diseases. We investigated whether pulvinar volume can be useful for differential diagnosis in ALS C9orf72 mutation carriers and noncarriers and how underlying functional connectivity changes affect this region.
METHODS
We studied 19 ALS C9orf72 mutation carriers (ALSC9+) accurately matched with wild-type ALS (ALSC9-) and ALS mimic (ALSmimic) patients using structural and resting-state functional magnetic resonance imaging data. Pulvinar volume was computed using automatic segmentation. Seed-to-voxel functional connectivity analyses were performed using seeds from a pulvinar functional parcellation.
RESULTS
Pulvinar structural integrity had high discriminative values for ALSC9+ patients compared to ALSmimic (area under the curve [AUC] = 0.86) and ALSC9- (AUC = 0.77) patients, yielding a volume cutpoint of approximately 0.23%. Compared to ALSmimic, ALSC9- showed increased anterior, inferior, and lateral pulvinar connections with bilateral occipital-temporal-parietal regions, whereas ALSC9+ showed no differences. ALSC9+ patients when compared to ALSC9- patients showed reduced pulvinar-occipital connectivity for anterior and inferior pulvinar seeds.
CONCLUSIONS
Pulvinar volume could be a differential biomarker closely related to the C9orf72 mutation. A pulvinar-cortical circuit dysfunction might play a critical role in disease progression and development, in both the genetic phenotype and ALS wild-type patients.
Topics: Aged; Female; Humans; Male; Middle Aged; Amyotrophic Lateral Sclerosis; C9orf72 Protein; Frontotemporal Dementia; Heterozygote; Magnetic Resonance Imaging; Mutation; Pulvinar
PubMed: 38469975
DOI: 10.1111/ene.16266 -
Clinical Neurophysiology : Official... May 2024This study investigated how high-definition transcranial direct current stimulation (HD-tDCS) over the primary motor cortex (M1) affects brain signal variability and... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study investigated how high-definition transcranial direct current stimulation (HD-tDCS) over the primary motor cortex (M1) affects brain signal variability and functional connectivity in the trigeminal pain pathway, and their association with changes in migraine attacks.
METHODS
Twenty-five episodic migraine patients were randomized for ten daily sessions of active or sham M1 HD-tDCS. Resting-state blood-oxygenation-level-dependent (BOLD) signal variability and seed-based functional connectivity were assessed pre- and post-treatment. A mediation analysis was performed to test whether BOLD signal variability mediates the relationship between treatment group and moderate-to-severe headache days.
RESULTS
The active M1 HD-tDCS group showed reduced BOLD variability in the spinal trigeminal nucleus (SpV) and thalamus, but increased variability in the rostral anterior cingulate cortex (rACC) compared to the sham group. Connectivity decreased between medial pulvinar-temporal pole, medial dorsal-precuneus, and the ventral posterior medial nucleus-SpV, but increased between the rACC-amygdala, and the periaqueductal gray-parahippocampal gyrus. Changes in medial pulvinar variability mediated the reduction in moderate-to-severe headache days at one-month post-treatment.
CONCLUSIONS
M1 HD-tDCS alters BOLD signal variability and connectivity in the trigeminal somatosensory and modulatory pain system, potentially alleviating migraine headache attacks.
SIGNIFICANCE
M1 HD-tDCS realigns brain signal variability and connectivity in migraineurs closer to healthy control levels.
Topics: Humans; Female; Migraine Disorders; Male; Motor Cortex; Adult; Transcranial Direct Current Stimulation; Magnetic Resonance Imaging; Middle Aged; Young Adult
PubMed: 38460220
DOI: 10.1016/j.clinph.2024.02.012 -
JAMA Psychiatry May 2024Posttraumatic stress disorder (PTSD) is a common psychiatric disorder that is particularly difficult to treat in military veterans. Noninvasive brain stimulation has... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Posttraumatic stress disorder (PTSD) is a common psychiatric disorder that is particularly difficult to treat in military veterans. Noninvasive brain stimulation has significant potential as a novel treatment to reduce PTSD symptoms.
OBJECTIVE
To test whether active transcranial direct current stimulation (tDCS) plus virtual reality (VR) is superior to sham tDCS plus VR for warzone-related PTSD.
DESIGN, SETTING, AND PARTICIPANTS
This double-blind randomized clinical trial was conducted among US military veterans enrolled from April 2018 to May 2023 at a secondary care Department of Veterans Affairs hospital and included 1- and 3-month follow-up visits. Participants included US military veterans with chronic PTSD and warzone-related exposure, recruited via referral and advertisement. Patients in psychiatric treatment had to be on a stable regimen for at least 6 weeks to be eligible for enrollment. Data were analyzed from May to September 2023.
INTERVENTION
Participants were randomly assigned to receive 2-mA anodal tDCS or sham tDCS targeted to the ventromedial prefrontal cortex, during six 25-minute sessions of standardized warzone VR exposure, delivered over 2 to 3 weeks.
MAIN OUTCOMES AND MEASURES
The co-primary outcomes were self-reported PTSD symptoms, measured via the PTSD checklist for DSM-5 (PCL-5), alongside quality of life. Other outcomes included psychophysiological arousal, clinician-assessed PTSD, depression, and social/occupational function.
RESULTS
A total of 54 participants (mean [SD] age, 45.7 [10.5] years; 51 [94%] males) were assessed, including 26 in the active tDCS group and 28 in the sham tDCS group. Participants in the active tDCS group reported a superior reduction in self-reported PTSD symptom severity at 1 month (t = -2.27, P = .02; Cohen d = -0.82). There were no significant differences in quality of life between active and sham tDCS groups. Active tDCS significantly accelerated psychophysiological habituation to VR events between sessions compared with sham tDCS (F5,7689.8 = 4.65; P < .001). Adverse effects were consistent with the known safety profile of the corresponding interventions.
CONCLUSIONS AND RELEVANCE
These findings suggest that combined tDCS plus VR may be a promising strategy for PTSD reduction and underscore the innovative potential of these combined technologies.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03372460.
Topics: Humans; Stress Disorders, Post-Traumatic; Transcranial Direct Current Stimulation; Male; Female; Double-Blind Method; Adult; Veterans; Middle Aged; Prefrontal Cortex; Virtual Reality Exposure Therapy; Virtual Reality
PubMed: 38446471
DOI: 10.1001/jamapsychiatry.2023.5661 -
Scientific Reports Feb 2024The rise in the global population of older adults underscores the significance to investigate age-related cognitive disorders and develop early treatment modalities....
The rise in the global population of older adults underscores the significance to investigate age-related cognitive disorders and develop early treatment modalities. Previous research suggests that non-invasive transcranial Alternating Current Stimulation (tACS) can moderately improve cognitive decline in older adults. However, non-declarative cognition has received relatively less attention. This study investigates whether repeated (16-day) bilateral theta-gamma cross-frequency tACS targeting the Dorsolateral Prefrontal Cortex (DLPFC) enhances non-declarative memory. Computerized cognitive training was applied alongside stimulation to control for the state-of-the-brain. The Alternating Serial Reaction Time (ASRT) task was employed to assess non-declarative functions such as visuomotor skill and probabilistic sequence learning. Results from 35 participants aged 55-82 indicated that active tACS led to more substantial improvements in visuomotor skills immediately after treatment, which persisted 3 months later, compared to sham tACS. Treatment benefit was more pronounced in older adults of younger age and those with pre-existing cognitive decline. However, neither intervention group exhibited modulation of probabilistic sequence learning. These results suggest that repeated theta-gamma tACS can selectively improve distinct non-declarative cognitive aspects when targeting the DLPFC. Our findings highlight the therapeutic potential of tACS in addressing deficits in learning and retaining general skills, which could have a positive impact on the quality of life for cognitively impaired older individuals by preserving independence in daily activities.
Topics: Humans; Aged; Transcranial Direct Current Stimulation; Quality of Life; Learning; Cognition; Brain
PubMed: 38418511
DOI: 10.1038/s41598-024-55125-2 -
Proceedings of the National Academy of... Mar 2024Music is powerful in conveying emotions and triggering affective brain mechanisms. Affective brain responses in previous studies were however rather inconsistent,...
Music is powerful in conveying emotions and triggering affective brain mechanisms. Affective brain responses in previous studies were however rather inconsistent, potentially because of the non-adaptive nature of recorded music used so far. Live music instead can be dynamic and adaptive and is often modulated in response to audience feedback to maximize emotional responses in listeners. Here, we introduce a setup for studying emotional responses to live music in a closed-loop neurofeedback setup. This setup linked live performances by musicians to neural processing in listeners, with listeners' amygdala activity was displayed to musicians in real time. Brain activity was measured using functional MRI, and especially amygdala activity was quantified in real time for the neurofeedback signal. Live pleasant and unpleasant piano music performed in response to amygdala neurofeedback from listeners was acoustically very different from comparable recorded music and elicited significantly higher and more consistent amygdala activity. Higher activity was also found in a broader neural network for emotion processing during live compared to recorded music. This finding included observations of the predominance for aversive coding in the ventral striatum while listening to unpleasant music, and involvement of the thalamic pulvinar nucleus, presumably for regulating attentional and cortical flow mechanisms. Live music also stimulated a dense functional neural network with the amygdala as a central node influencing other brain systems. Finally, only live music showed a strong and positive coupling between features of the musical performance and brain activity in listeners pointing to real-time and dynamic entrainment processes.
Topics: Music; Brain; Emotions; Amygdala; Affect; Magnetic Resonance Imaging; Auditory Perception
PubMed: 38408255
DOI: 10.1073/pnas.2316306121 -
Parkinsonism & Related Disorders Apr 2024Connector hubs are specialized brain regions that connect multiple brain networks and therefore have the potential to affect the functions of multiple systems. This...
INTRODUCTION
Connector hubs are specialized brain regions that connect multiple brain networks and therefore have the potential to affect the functions of multiple systems. This study aims to examine the involvement of connector hub regions in essential tremor.
METHODS
We examined whole-brain functional connectivity alterations across multiple brain networks in 27 patients with essential tremor and 27 age- and sex-matched healthy controls to identify affected hub regions using a network metric called functional connectivity overlap ratio estimated from resting-state functional MRI. We also evaluated the relationships of affected hubs with cognitive and tremor scores in all patients and with motor function improvement scores in 15 patients who underwent postoperative follow-up evaluations after focused ultrasound thalamotomy.
RESULTS
We have identified affected connector hubs in the cerebellum and thalamus. Specifically, the dentate nucleus in the cerebellum and the dorsomedial thalamus exhibited more extensive connections with the sensorimotor network in patients. Moreover, the connections of the thalamic pulvinar with the visual network were also significantly widespread in the patient group. The connections of these connector hub regions with cognitive networks were negatively associated (FDR q < 0.05) with cognitive, tremor, and motor function improvement scores.
CONCLUSION
In patients with essential tremor, connector hub regions within the cerebellum and thalamus exhibited widespread functional connections with sensorimotor and visual networks, leading to alternative pathways outside the classical tremor axis. Their connections with cognitive networks also affect patients' cognitive function.
Topics: Humans; Essential Tremor; Tremor; Magnetic Resonance Imaging; Thalamus; Cerebellum; Cognition
PubMed: 38382401
DOI: 10.1016/j.parkreldis.2024.106034 -
Cureus Jan 2024Understanding the role of the pulvinar nucleus may be critical for guiding circuit-targeted neurosurgical intervention in some patients. In this report, a 33-year-old...
Understanding the role of the pulvinar nucleus may be critical for guiding circuit-targeted neurosurgical intervention in some patients. In this report, a 33-year-old female presented with focal onset occipital epilepsy with secondary generalization and with a previously radiated arteriovenous malformation within the right primary visual cortex. Phase II monitoring demonstrated the pulvinar nucleus was not involved in subclinical seizures restricted to the primary visual cortex, but it did become involved in clinical events with more extensive seizure spread into higher visual cortical regions. She underwent responsive neurostimulation (RNS) with implantation of leads within the primary visual cortex. This case demonstrates the late propagation of epileptic activity from the visual cortex to the pulvinar nucleus and illustrates the pulvinar nucleus' connections with higher-order visual areas.
PubMed: 38371112
DOI: 10.7759/cureus.52534 -
Alzheimer's & Dementia (New York, N. Y.) 2024Emotionally driven cognitive complaints represent a major diagnostic challenge for clinicians and indicate the importance of objective confirmation of the accuracy of...
INTRODUCTION
Emotionally driven cognitive complaints represent a major diagnostic challenge for clinicians and indicate the importance of objective confirmation of the accuracy of depressive patients' descriptions of their cognitive symptoms.
METHODS
We compared cognitive status and structural and functional brain connectivity changes in the pulvinar and hippocampus between patients with total depression and healthy controls. The depressive group was also classified as "amnestic" or "nonamnestic," based on the members' subjective reports concerning their forgetfulness. We then sought to determine whether these patients would differ in terms of objective neuroimaging and cognitive findings.
RESULTS
The right pulvinar exhibited altered connectivity in individuals with depression with objective cognitive impairment, a finding which was not apparent in depressive patients with subjective cognitive impairment.
DISCUSSION
The pulvinar may play a role in depression-related cognitive impairments. Connectivity network changes may differ between objective and subjective cognitive impairment in depression and may play a role in the increased risk of dementia in patients with depression.
PubMed: 38356480
DOI: 10.1002/trc2.12450