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2.
Alzheimers Res Ther ; 16(1): 119, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822365

ABSTRACT

BACKGROUND: Autopsy work reported that neuronal density in the locus coeruleus (LC) provides neural reserve against cognitive decline in dementia. Recent neuroimaging and pharmacological studies reported that left frontoparietal network functional connectivity (LFPN-FC) confers resilience against beta-amyloid (Aß)-related cognitive decline in preclinical sporadic and autosomal dominant Alzheimer's disease (AD), as well as against LC-related cognitive changes. Given that the LFPN and the LC play important roles in attention, and attention deficits have been observed early in the disease process, we examined whether LFPN-FC and LC structural health attenuate attentional decline in the context of AD pathology. METHODS: 142 participants from the Harvard Aging Brain Study who underwent resting-state functional MRI, LC structural imaging, PiB(Aß)-PET, and up to 5 years of cognitive follow-ups were included (mean age = 74.5 ± 9.9 years, 89 women). Cross-sectional robust linear regression associated LC integrity (measured as the average of five continuous voxels with the highest intensities in the structural LC images) or LFPN-FC with Digit Symbol Substitution Test (DSST) performance at baseline. Longitudinal robust mixed effect analyses examined associations between DSST decline and (i) two-way interactions of baseline LC integrity (or LFPN-FC) and PiB or (ii) the three-way interaction of baseline LC integrity, LFPN-FC, and PiB. Baseline age, sex, and years of education were included as covariates. RESULTS: At baseline, lower LFPN-FC, but not LC integrity, was related to worse DSST performance. Longitudinally, lower baseline LC integrity was associated with a faster DSST decline, especially at PiB > 10.38 CL. Lower baseline LFPN-FC was associated with a steeper decline on the DSST but independent of PiB. At elevated PiB levels (> 46 CL), higher baseline LFPN-FC was associated with an attenuated decline on the DSST, despite the presence of lower LC integrity. CONCLUSIONS: Our findings demonstrate that the LC can provide resilience against Aß-related attention decline. However, when Aß accumulates and the LC's resources may be depleted, the functioning of cortical target regions of the LC, such as the LFPN-FC, can provide additional resilience to sustain attentional performance in preclinical AD. These results provide critical insights into the neural correlates contributing to individual variability at risk versus resilience against Aß-related cognitive decline.


Subject(s)
Alzheimer Disease , Locus Coeruleus , Magnetic Resonance Imaging , Parietal Lobe , Humans , Female , Male , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/psychology , Alzheimer Disease/physiopathology , Aged , Locus Coeruleus/diagnostic imaging , Locus Coeruleus/pathology , Magnetic Resonance Imaging/methods , Parietal Lobe/diagnostic imaging , Aged, 80 and over , Attention/physiology , Frontal Lobe/diagnostic imaging , Frontal Lobe/physiopathology , Positron-Emission Tomography , Cross-Sectional Studies , Neural Pathways/diagnostic imaging , Neural Pathways/physiopathology , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/psychology , Neuropsychological Tests
3.
CNS Neurosci Ther ; 30(6): e14786, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38828694

ABSTRACT

PURPOSE: To investigate dynamic functional connectivity (dFC) within the cerebellar-whole brain network and dynamic topological properties of the cerebellar network in obstructive sleep apnea (OSA) patients. METHODS: Sixty male patients and 60 male healthy controls were included. The sliding window method examined the fluctuations in cerebellum-whole brain dFC and connection strength in OSA. Furthermore, graph theory metrics evaluated the dynamic topological properties of the cerebellar network. Additionally, hidden Markov modeling validated the robustness of the dFC. The correlations between the abovementioned measures and clinical assessments were assessed. RESULTS: Two dynamic network states were characterized. State 2 exhibited a heightened frequency, longer fractional occupancy, and greater mean dwell time in OSA. The cerebellar networks and cerebrocerebellar dFC alterations were mainly located in the default mode network, frontoparietal network, somatomotor network, right cerebellar CrusI/II, and other networks. Global properties indicated aberrant cerebellar topology in OSA. Dynamic properties were correlated with clinical indicators primarily on emotion, cognition, and sleep. CONCLUSION: Abnormal dFC in male OSA may indicate an imbalance between the integration and segregation of brain networks, concurrent with global topological alterations. Abnormal default mode network interactions with high-order and low-level cognitive networks, disrupting their coordination, may impair the regulation of cognitive, emotional, and sleep functions in OSA.


Subject(s)
Cerebellum , Nerve Net , Sleep Apnea, Obstructive , Humans , Male , Sleep Apnea, Obstructive/physiopathology , Sleep Apnea, Obstructive/diagnostic imaging , Cerebellum/diagnostic imaging , Cerebellum/physiopathology , Middle Aged , Adult , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Magnetic Resonance Imaging , Connectome , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging , Default Mode Network/physiopathology , Default Mode Network/diagnostic imaging
4.
Cereb Cortex ; 34(6)2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38836288

ABSTRACT

Major depressive disorder demonstrated sex differences in prevalence and symptoms, which were more pronounced during adolescence. Yet, research on sex-specific brain network characteristics in adolescent-onset major depressive disorder remains limited. This study investigated sex-specific and nonspecific alterations in resting-state functional connectivity of three core networks (frontoparietal network, salience network, and default mode network) and subcortical networks in adolescent-onset major depressive disorder, using seed-based resting-state functional connectivity in 50 medication-free patients with adolescent-onset major depressive disorder and 56 healthy controls. Irrespective of sex, compared with healthy controls, adolescent-onset major depressive disorder patients showed hypoconnectivity between bilateral hippocampus and right superior temporal gyrus (default mode network). More importantly, we further found that females with adolescent-onset major depressive disorder exhibited hypoconnectivity within the default mode network (medial prefrontal cortex), and between the subcortical regions (i.e. amygdala, striatum, and thalamus) with the default mode network (angular gyrus and posterior cingulate cortex) and the frontoparietal network (dorsal prefrontal cortex), while the opposite patterns of resting-state functional connectivity alterations were observed in males with adolescent-onset major depressive disorder, relative to their sex-matched healthy controls. Moreover, several sex-specific resting-state functional connectivity changes were correlated with age of onset, sleep disturbance, and anxiety in adolescent-onset major depressive disorder with different sex. These findings suggested that these sex-specific resting-state functional connectivity alterations may reflect the differences in brain development or processes related to early illness onset, underscoring the necessity for sex-tailored diagnostic and therapeutic approaches in adolescent-onset major depressive disorder.


Subject(s)
Brain , Depressive Disorder, Major , Magnetic Resonance Imaging , Nerve Net , Sex Characteristics , Humans , Depressive Disorder, Major/physiopathology , Depressive Disorder, Major/diagnostic imaging , Female , Adolescent , Male , Brain/physiopathology , Brain/diagnostic imaging , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging , Young Adult , Age of Onset , Brain Mapping , Default Mode Network/physiopathology , Default Mode Network/diagnostic imaging
5.
Elife ; 122024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829200

ABSTRACT

Threat-response neural circuits are conserved across species and play roles in normal behavior and psychiatric diseases. Maladaptive changes in these neural circuits contribute to stress, mood, and anxiety disorders. Active coping in response to stressors is a psychosocial factor associated with resilience against stress-induced mood and anxiety disorders. The neural circuitry underlying active coping is poorly understood, but the functioning of these circuits could be key for overcoming anxiety and related disorders. The supramammillary nucleus (SuM) has been suggested to be engaged by threat. SuM has many projections and a poorly understood diversity of neural populations. In studies using mice, we identified a unique population of glutamatergic SuM neurons (SuMVGLUT2+::POA) based on projection to the preoptic area of the hypothalamus (POA) and found SuMVGLUT2+::POA neurons have extensive arborizations. SuMVGLUT2+::POA neurons project to brain areas that mediate features of the stress and threat responses including the paraventricular nucleus thalamus (PVT), periaqueductal gray (PAG), and habenula (Hb). Thus, SuMVGLUT2+::POA neurons are positioned as a hub, connecting to areas implicated in regulating stress responses. Here we report SuMVGLUT2+::POA neurons are recruited by diverse threatening stressors, and recruitment correlated with active coping behaviors. We found that selective photoactivation of the SuMVGLUT2+::POA population drove aversion but not anxiety like behaviors. Activation of SuMVGLUT2+::POA neurons in the absence of acute stressors evoked active coping like behaviors and drove instrumental behavior. Also, activation of SuMVGLUT2+::POA neurons was sufficient to convert passive coping strategies to active behaviors during acute stress. In contrast, we found activation of GABAergic (VGAT+) SuM neurons (SuMVGAT+) neurons did not alter drive aversion or active coping, but termination of photostimulation was followed by increased mobility in the forced swim test. These findings establish a new node in stress response circuitry that has projections to many brain areas and evokes flexible active coping behaviors.


Subject(s)
Adaptation, Psychological , Neurons , Stress, Psychological , Animals , Neurons/physiology , Neurons/metabolism , Mice , Adaptation, Psychological/physiology , Male , Glutamic Acid/metabolism , Hypothalamus, Posterior/physiology , Neural Pathways/physiology , Mice, Inbred C57BL
6.
BMC Psychol ; 12(1): 324, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38831468

ABSTRACT

Cognitive functions, such as learning and memory processes, depend on effective communication between brain regions which is facilitated by white matter tracts (WMT). We investigated the microstructural properties and the contribution of WMT to extinction learning and memory in a predictive learning task. Forty-two healthy participants completed an extinction learning paradigm without a fear component. We examined differences in microstructural properties using diffusion tensor imaging to identify underlying neural connectivity and structural correlates of extinction learning and their potential implications for the renewal effect. Participants with good acquisition performance exhibited higher fractional anisotropy (FA) in WMT including the bilateral inferior longitudinal fasciculus (ILF) and the right temporal part of the cingulum (CNG). This indicates enhanced connectivity and communication between brain regions relevant to learning and memory resulting in better learning performance. Our results suggest that successful acquisition and extinction performance were linked to enhanced structural connectivity. Lower radial diffusivity (RD) in the right ILF and right temporal part of the CNG was observed for participants with good acquisition learning performance. This observation suggests that learning difficulties associated with increased RD may potentially be due to less myelinated axons in relevant WMT. Also, participants with good acquisition performance were more likely to show a renewal effect. The results point towards a potential role of structural integrity in extinction-relevant WMT for acquisition and extinction.


Subject(s)
Diffusion Tensor Imaging , Extinction, Psychological , White Matter , Humans , Male , Female , Diffusion Tensor Imaging/methods , White Matter/diagnostic imaging , Adult , Young Adult , Extinction, Psychological/physiology , Learning/physiology , Neural Pathways/diagnostic imaging , Gyrus Cinguli/diagnostic imaging , Gyrus Cinguli/anatomy & histology , Anisotropy
7.
Cereb Cortex ; 34(6)2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38847535

ABSTRACT

Given the widespread use and relapse of methamphetamine (METH), it has caused serious public health burdens globally. However, the neurobiological basis of METH addiction remains poorly understood. Therefore, this study aimed to use magnetic resonance imaging (MRI) to investigate changes in brain networks and their connection to impulsivity and drug craving in abstinent individuals with METH use disorder (MUDs). A total of 110 MUDs and 55 age- and gender-matched healthy controls (HCs) underwent resting-state functional MRI and T1-weighted imaging scans, and completed impulsivity and cue-induced craving measurements. We applied independent component analysis to construct functional brain networks and multivariate analysis of covariance to investigate group differences in network connectivity. Mediation analyses were conducted to explore the relationships among brain-network functional connectivity (FC), impulsivity, and drug craving in the patients. MUDs showed increased connectivity in the salience network (SN) and decreased connectivity in the default mode network compared to HCs. Impulsivity was positively correlated with FC within the SN and played a completely mediating role between METH craving and FC within the SN in MUDs. These findings suggest alterations in functional brain networks underlying METH dependence, with SN potentially acting as a core neural substrate for impulse control disorders.


Subject(s)
Amphetamine-Related Disorders , Brain , Craving , Cues , Impulsive Behavior , Magnetic Resonance Imaging , Methamphetamine , Humans , Male , Amphetamine-Related Disorders/diagnostic imaging , Amphetamine-Related Disorders/physiopathology , Amphetamine-Related Disorders/psychology , Adult , Craving/physiology , Impulsive Behavior/physiology , Female , Brain/diagnostic imaging , Brain/physiopathology , Methamphetamine/adverse effects , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging , Young Adult
9.
Nat Commun ; 15(1): 3542, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38719802

ABSTRACT

Understanding the functional connectivity between brain regions and its emergent dynamics is a central challenge. Here we present a theory-experiment hybrid approach involving iteration between a minimal computational model and in vivo electrophysiological measurements. Our model not only predicted spontaneous persistent activity (SPA) during Up-Down-State oscillations, but also inactivity (SPI), which has never been reported. These were confirmed in vivo in the membrane potential of neurons, especially from layer 3 of the medial and lateral entorhinal cortices. The data was then used to constrain two free parameters, yielding a unique, experimentally determined model for each neuron. Analytic and computational analysis of the model generated a dozen quantitative predictions about network dynamics, which were all confirmed in vivo to high accuracy. Our technique predicted functional connectivity; e. g. the recurrent excitation is stronger in the medial than lateral entorhinal cortex. This too was confirmed with connectomics data. This technique uncovers how differential cortico-entorhinal dialogue generates SPA and SPI, which could form an energetically efficient working-memory substrate and influence the consolidation of memories during sleep. More broadly, our procedure can reveal the functional connectivity of large networks and a theory of their emergent dynamics.


Subject(s)
Entorhinal Cortex , Models, Neurological , Neurons , Entorhinal Cortex/physiology , Animals , Neurons/physiology , Male , Connectome , Nerve Net/physiology , Membrane Potentials/physiology , Neural Pathways/physiology , Computer Simulation , Mice
10.
Cereb Cortex ; 34(5)2024 May 02.
Article in English | MEDLINE | ID: mdl-38725293

ABSTRACT

Numerous studies reported inconsistent results concerning gender influences on the functional organization of the brain for language in children and adults. However, data for the gender differences in the functional language networks at birth are sparse. Therefore, we investigated gender differences in resting-state functional connectivity in the language-related brain regions in newborns using functional near-infrared spectroscopy. The results revealed that female newborns demonstrated significantly stronger functional connectivities between the superior temporal gyri and middle temporal gyri, the superior temporal gyri and the Broca's area in the right hemisphere, as well as between the right superior temporal gyri and left Broca's area. Nevertheless, statistical analysis failed to reveal functional lateralization of the language-related brain areas in resting state in both groups. Together, these results suggest that the onset of language system might start earlier in females, because stronger functional connectivities in the right brain in female neonates were probably shaped by the processing of prosodic information, which mainly constitutes newborns' first experiences of speech in the womb. More exposure to segmental information after birth may lead to strengthened functional connectivities in the language system in both groups, resulting in a stronger leftward lateralization in males and a more balanced or leftward dominance in females.


Subject(s)
Language , Sex Characteristics , Spectroscopy, Near-Infrared , Humans , Female , Spectroscopy, Near-Infrared/methods , Male , Infant, Newborn , Brain/physiology , Brain/diagnostic imaging , Rest/physiology , Functional Laterality/physiology , Neural Pathways/physiology , Brain Mapping/methods
11.
Behav Brain Funct ; 20(1): 11, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38724963

ABSTRACT

Procrastination is universally acknowledged as a problematic behavior with wide-ranging consequences impacting various facets of individuals' lives, including academic achievement, social accomplishments, and mental health. Although previous research has indicated that future self-continuity is robustly negatively correlated with procrastination, it remains unknown about the neural mechanisms underlying the impact of future self-continuity on procrastination. To address this issue, we employed a free construction approach to collect individuals' episodic future thinking (EFT) thoughts regarding specific procrastination tasks. Next, we conducted voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) analysis to explore the neural substrates underlying future self-continuity. Behavior results revealed that future self-continuity was significantly negatively correlated with procrastination, and positively correlated with anticipated positive outcome. The VBM analysis showed a positive association between future self-continuity and gray matter volumes in the right ventromedial prefrontal cortex (vmPFC). Furthermore, the RSFC results indicated that the functional connectivity between the right vmPFC and the left inferior parietal lobule (IPL) was positively correlated with future self-continuity. More importantly, the mediation analysis demonstrated that anticipated positive outcome can completely mediate the relationship between the vmPFC-IPL functional connectivity and procrastination. These findings suggested that vmPFC-IPL functional connectivity might prompt anticipated positive outcome about the task and thereby reduce procrastination, which provides a new perspective to understand the relationship between future self-continuity and procrastination.


Subject(s)
Magnetic Resonance Imaging , Parietal Lobe , Prefrontal Cortex , Procrastination , Humans , Procrastination/physiology , Male , Female , Magnetic Resonance Imaging/methods , Young Adult , Adult , Prefrontal Cortex/physiology , Prefrontal Cortex/diagnostic imaging , Parietal Lobe/physiology , Parietal Lobe/diagnostic imaging , Brain Mapping/methods , Neural Pathways/physiology , Adolescent , Nerve Net/diagnostic imaging , Nerve Net/physiology , Thinking/physiology
12.
Cereb Cortex ; 34(13): 19-29, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38696600

ABSTRACT

While fronto-posterior underconnectivity has often been reported in autism, it was shown that different contexts may modulate between-group differences in functional connectivity. Here, we assessed how different task paradigms modulate functional connectivity differences in a young autistic sample relative to typically developing children. Twenty-three autistic and 23 typically developing children aged 6 to 15 years underwent functional magnetic resonance imaging (fMRI) scanning while completing a reasoning task with visuospatial versus semantic content. We observed distinct connectivity patterns in autistic versus typical children as a function of task type (visuospatial vs. semantic) and problem complexity (visual matching vs. reasoning), despite similar performance. For semantic reasoning problems, there was no significant between-group differences in connectivity. However, during visuospatial reasoning problems, we observed occipital-occipital, occipital-temporal, and occipital-frontal over-connectivity in autistic children relative to typical children. Also, increasing the complexity of visuospatial problems resulted in increased functional connectivity between occipital, posterior (temporal), and anterior (frontal) brain regions in autistic participants, more so than in typical children. Our results add to several studies now demonstrating that the connectivity alterations in autistic relative to neurotypical individuals are much more complex than previously thought and depend on both task type and task complexity and their respective underlying cognitive processes.


Subject(s)
Autistic Disorder , Brain , Magnetic Resonance Imaging , Semantics , Humans , Child , Male , Adolescent , Female , Autistic Disorder/physiopathology , Autistic Disorder/diagnostic imaging , Autistic Disorder/psychology , Brain/diagnostic imaging , Brain/physiopathology , Brain Mapping , Space Perception/physiology , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging
13.
Addict Biol ; 29(5): e13399, 2024 May.
Article in English | MEDLINE | ID: mdl-38711213

ABSTRACT

Excessive use of the internet, which is a typical scenario of self-control failure, could lead to potential consequences such as anxiety, depression, and diminished academic performance. However, the underlying neuropsychological mechanisms remain poorly understood. This study aims to investigate the structural basis of self-control and internet addiction. In a cohort of 96 internet gamers, we examined the relationships among grey matter volume and white matter integrity within the frontostriatal circuits and internet addiction severity, as well as self-control measures. The results showed a significant and negative correlation between dACC grey matter volume and internet addiction severity (p < 0.001), but not with self-control. Subsequent tractography from the dACC to the bilateral ventral striatum (VS) was conducted. The fractional anisotropy (FA) and radial diffusivity of dACC-right VS pathway was negatively (p = 0.011) and positively (p = 0.020) correlated with internet addiction severity, respectively, and the FA was also positively correlated with self-control (p = 0.036). These associations were not observed for the dACC-left VS pathway. Further mediation analysis demonstrated a significant complete mediation effect of self-control on the relationship between FA of the dACC-right VS pathway and internet addiction severity. Our findings suggest that the dACC-right VS pathway is a critical neural substrate for both internet addiction and self-control. Deficits in this pathway may lead to impaired self-regulation over internet usage, exacerbating the severity of internet addiction.


Subject(s)
Diffusion Tensor Imaging , Gray Matter , Internet Addiction Disorder , Self-Control , White Matter , Humans , White Matter/diagnostic imaging , White Matter/pathology , Male , Internet Addiction Disorder/diagnostic imaging , Internet Addiction Disorder/physiopathology , Female , Diffusion Tensor Imaging/methods , Adult , Young Adult , Gray Matter/diagnostic imaging , Gray Matter/pathology , Ventral Striatum/diagnostic imaging , Ventral Striatum/physiopathology , Ventral Striatum/pathology , Severity of Illness Index , Neural Pathways/diagnostic imaging , Neural Pathways/physiopathology , Corpus Striatum/diagnostic imaging , Corpus Striatum/pathology , Corpus Striatum/physiopathology , Internet , Frontal Lobe/diagnostic imaging , Frontal Lobe/pathology , Frontal Lobe/physiopathology
14.
Neural Plast ; 2024: 8862647, 2024.
Article in English | MEDLINE | ID: mdl-38715980

ABSTRACT

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that is characterized by inattention, hyperactivity, and impulsivity. The neural mechanisms underlying ADHD remain inadequately understood, and current approaches do not well link neural networks and attention networks within brain networks. Our objective is to investigate the neural mechanisms related to attention and explore neuroimaging biological tags that can be generalized within the attention networks. In this paper, we utilized resting-state functional magnetic resonance imaging data to examine the differential functional connectivity network between ADHD and typically developing individuals. We employed a graph convolutional neural network model to identify individuals with ADHD. After classification, we visualized brain regions with significant contributions to the classification results. Our results suggest that the frontal, temporal, parietal, and cerebellar regions are likely the primary areas of dysfunction in individuals with ADHD. We also explored the relationship between regions of interest and attention networks, as well as the connection between crucial nodes and the distribution of positively and negatively correlated connections. This analysis allowed us to pinpoint the most discriminative brain regions, including the right orbitofrontal gyrus, the left rectus gyrus and bilateral insula, the right inferior temporal gyrus and bilateral transverse temporal gyrus in the temporal region, and the lingual gyrus of the occipital lobe, multiple regions of the basal ganglia and the upper cerebellum. These regions are primarily involved in the attention executive control network and the attention orientation network. Dysfunction in the functional connectivity of these regions may contribute to the underlying causes of ADHD.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Brain , Magnetic Resonance Imaging , Neural Networks, Computer , Humans , Attention Deficit Disorder with Hyperactivity/physiopathology , Attention Deficit Disorder with Hyperactivity/diagnostic imaging , Magnetic Resonance Imaging/methods , Male , Female , Brain/physiopathology , Brain/diagnostic imaging , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Adult , Brain Mapping/methods , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging , Young Adult , Adolescent , Child , Attention/physiology
15.
J Psychiatry Neurosci ; 49(3): E157-E171, 2024.
Article in English | MEDLINE | ID: mdl-38692693

ABSTRACT

BACKGROUND: Critical adolescent neural refinement is controlled by the DCC (deleted in colorectal cancer) protein, a receptor for the netrin-1 guidance cue. We sought to describe the effects of reduced DCC on neuroanatomy in the adolescent and adult mouse brain. METHODS: We examined neuronal connectivity, structural covariance, and molecular processes in a DCC-haploinsufficient mouse model, compared with wild-type mice, using new, custom analytical tools designed to leverage publicly available databases from the Allen Institute. RESULTS: We included 11 DCC-haploinsufficient mice and 16 wild-type littermates. Neuroanatomical effects of DCC haploinsufficiency were more severe in adolescence than adulthood and were largely restricted to the mesocorticolimbic dopamine system. The latter finding was consistent whether we identified the regions of the mesocorticolimbic dopamine system a priori or used connectivity data from the Allen Brain Atlas to determine de novo where these dopamine axons terminated. Covariance analyses found that DCC haploinsufficiency disrupted the coordinated development of the brain regions that make up the mesocorticolimbic dopamine system. Gene expression maps pointed to molecular processes involving the expression of DCC, UNC5C (encoding DCC's co-receptor), and NTN1 (encoding its ligand, netrin-1) as underlying our structural findings. LIMITATIONS: Our study involved a single sex (males) at only 2 ages. CONCLUSION: The neuroanatomical phenotype of DCC haploinsufficiency described in mice parallels that observed in DCC-haploinsufficient humans. It is critical to understand the DCC-haploinsufficient mouse as a clinically relevant model system.


Subject(s)
Brain , DCC Receptor , Dopamine , Haploinsufficiency , Animals , DCC Receptor/genetics , Brain/metabolism , Brain/growth & development , Brain/anatomy & histology , Dopamine/metabolism , Mice , Male , Gene Expression , Neural Pathways , Age Factors , Female , Mice, Inbred C57BL , Aging/genetics , Aging/physiology
16.
Cereb Cortex ; 34(13): 30-39, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38696599

ABSTRACT

The amygdala undergoes a period of overgrowth in the first year of life, resulting in enlarged volume by 12 months in infants later diagnosed with ASD. The overgrowth of the amygdala may have functional consequences during infancy. We investigated whether amygdala connectivity differs in 12-month-olds at high likelihood (HL) for ASD (defined by having an older sibling with autism), compared to those at low likelihood (LL). We examined seed-based connectivity of left and right amygdalae, hypothesizing that the HL and LL groups would differ in amygdala connectivity, especially with the visual cortex, based on our prior reports demonstrating that components of visual circuitry develop atypically and are linked to genetic liability for autism. We found that HL infants exhibited weaker connectivity between the right amygdala and the left visual cortex, as well as between the left amygdala and the right anterior cingulate, with evidence that these patterns occur in distinct subgroups of the HL sample. Amygdala connectivity strength with the visual cortex was related to motor and communication abilities among HL infants. Findings indicate that aberrant functional connectivity between the amygdala and visual regions is apparent in infants with genetic liability for ASD and may have implications for early differences in adaptive behaviors.


Subject(s)
Amygdala , Magnetic Resonance Imaging , Visual Cortex , Humans , Amygdala/diagnostic imaging , Amygdala/physiopathology , Male , Female , Infant , Visual Cortex/diagnostic imaging , Visual Cortex/physiopathology , Visual Cortex/growth & development , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging , Autistic Disorder/genetics , Autistic Disorder/physiopathology , Autistic Disorder/diagnostic imaging , Autism Spectrum Disorder/genetics , Autism Spectrum Disorder/physiopathology , Autism Spectrum Disorder/diagnostic imaging , Genetic Predisposition to Disease/genetics
17.
Addict Biol ; 29(5): e13400, 2024 May.
Article in English | MEDLINE | ID: mdl-38706091

ABSTRACT

Substance use disorders are characterized by inhibition deficits related to disrupted connectivity in white matter pathways, leading via interaction to difficulties in resisting substance use. By combining neuroimaging with smartphone-based ecological momentary assessment (EMA), we questioned how biomarkers moderate inhibition deficits to predict use. Thus, we aimed to assess white matter integrity interaction with everyday inhibition deficits and related resting-state network connectivity to identify multi-dimensional predictors of substance use. Thirty-eight patients treated for alcohol, cannabis or tobacco use disorder completed 1 week of EMA to report substance use five times and complete Stroop inhibition testing twice daily. Before EMA tracking, participants underwent resting state functional MRI and diffusion tensor imaging (DTI) scanning. Regression analyses were conducted between mean Stroop performances and whole-brain fractional anisotropy (FA) in white matter. Moderation testing was conducted between mean FA within significant clusters as moderator and the link between momentary Stroop performance and use as outcome. Predictions between FA and resting-state connectivity strength in known inhibition-related networks were assessed using mixed modelling. Higher FA values in the anterior corpus callosum and bilateral anterior corona radiata predicted higher mean Stroop performance during the EMA week and stronger functional connectivity in occipital-frontal-cerebellar regions. Integrity in these regions moderated the link between inhibitory control and substance use, whereby stronger inhibition was predictive of the lowest probability of use for the highest FA values. In conclusion, compromised white matter structural integrity in anterior brain systems appears to underlie impairment in inhibitory control functional networks and compromised ability to refrain from substance use.


Subject(s)
Diffusion Tensor Imaging , Inhibition, Psychological , Magnetic Resonance Imaging , White Matter , Humans , White Matter/diagnostic imaging , White Matter/pathology , Male , Female , Adult , Ecological Momentary Assessment , Substance-Related Disorders/physiopathology , Substance-Related Disorders/diagnostic imaging , Stroop Test , Alcoholism/physiopathology , Alcoholism/diagnostic imaging , Brain/diagnostic imaging , Brain/physiopathology , Middle Aged , Tobacco Use Disorder/physiopathology , Tobacco Use Disorder/diagnostic imaging , Marijuana Abuse/physiopathology , Marijuana Abuse/diagnostic imaging , Corpus Callosum/diagnostic imaging , Corpus Callosum/pathology , Smartphone , Neural Pathways/diagnostic imaging , Neural Pathways/physiopathology , Anisotropy , Young Adult
18.
Front Neural Circuits ; 18: 1384621, 2024.
Article in English | MEDLINE | ID: mdl-38736977

ABSTRACT

The posterior intralaminar thalamic nucleus (PIL) and peripeduncular nucleus (PP) are two adjoining structures located medioventral to the medial geniculate nucleus. The PIL-PP region plays important roles in auditory fear conditioning and in social, maternal and sexual behaviors. Previous studies often lumped the PIL and PP into single entity, and therefore it is not known if they have common and/or different brain-wide connections. In this study, we investigate brain-wide efferent and afferent projections of the PIL and PP using reliable anterograde and retrograde tracing methods. Both PIL and PP project strongly to lateral, medial and anterior basomedial amygdaloid nuclei, posteroventral striatum (putamen and external globus pallidus), amygdalostriatal transition area, zona incerta, superior and inferior colliculi, and the ectorhinal cortex. However, the PP rather than the PIL send stronger projections to the hypothalamic regions such as preoptic area/nucleus, anterior hypothalamic nucleus, and ventromedial nucleus of hypothalamus. As for the afferent projections, both PIL and PP receive multimodal information from auditory (inferior colliculus, superior olivary nucleus, nucleus of lateral lemniscus, and association auditory cortex), visual (superior colliculus and ectorhinal cortex), somatosensory (gracile and cuneate nuclei), motor (external globus pallidus), and limbic (central amygdaloid nucleus, hypothalamus, and insular cortex) structures. However, the PP rather than PIL receives strong projections from the visual related structures parabigeminal nucleus and ventral lateral geniculate nucleus. Additional results from Cre-dependent viral tracing in mice have also confirmed the main results in rats. Together, the findings in this study would provide new insights into the neural circuits and functional correlation of the PIL and PP.


Subject(s)
Intralaminar Thalamic Nuclei , Neural Pathways , Animals , Rats , Mice , Male , Neural Pathways/physiology , Intralaminar Thalamic Nuclei/physiology , Mice, Inbred C57BL , Rats, Sprague-Dawley , Female
19.
Cereb Cortex ; 34(5)2024 May 02.
Article in English | MEDLINE | ID: mdl-38741270

ABSTRACT

This study extends the application of the frequency-domain new causality method to functional magnetic resonance imaging analysis. Strong causality, weak causality, balanced causality, cyclic causality, and transitivity causality were constructed to simulate varying degrees of causal associations among multivariate functional-magnetic-resonance-imaging blood-oxygen-level-dependent signals. Data from 1,252 groups of individuals with different degrees of cognitive impairment were collected. The frequency-domain new causality method was employed to construct directed efficient connectivity networks of the brain, analyze the statistical characteristics of topological variations in brain regions related to cognitive impairment, and utilize these characteristics as features for training a deep learning model. The results demonstrated that the frequency-domain new causality method accurately detected causal associations among simulated signals of different degrees. The deep learning tests also confirmed the superior performance of new causality, surpassing the other three methods in terms of accuracy, precision, and recall rates. Furthermore, consistent significant differences were observed in the brain efficiency networks, where several subregions defined by the multimodal parcellation method of Human Connectome Project simultaneously appeared in the topological statistical results of different patient groups. This suggests a significant association between these fine-grained cortical subregions, driven by multimodal data segmentation, and human cognitive function, making them potential biomarkers for further analysis of Alzheimer's disease.


Subject(s)
Brain , Connectome , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Male , Female , Connectome/methods , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/physiopathology , Cognition/physiology , Aged , Middle Aged , Deep Learning , Nerve Net/diagnostic imaging , Nerve Net/physiology , Neural Pathways/diagnostic imaging , Neural Pathways/physiopathology , Nervous System Diseases/diagnostic imaging , Nervous System Diseases/physiopathology , Adult
20.
Cereb Cortex ; 34(5)2024 May 02.
Article in English | MEDLINE | ID: mdl-38741271

ABSTRACT

This study investigates abnormalities in cerebellar-cerebral static and dynamic functional connectivity among patients with acute pontine infarction, examining the relationship between these connectivity changes and behavioral dysfunction. Resting-state functional magnetic resonance imaging was utilized to collect data from 45 patients within seven days post-pontine infarction and 34 normal controls. Seed-based static and dynamic functional connectivity analyses identified divergences in cerebellar-cerebral connectivity features between pontine infarction patients and normal controls. Correlations between abnormal functional connectivity features and behavioral scores were explored. Compared to normal controls, left pontine infarction patients exhibited significantly increased static functional connectivity within the executive, affective-limbic, and motor networks. Conversely, right pontine infarction patients demonstrated decreased static functional connectivity in the executive, affective-limbic, and default mode networks, alongside an increase in the executive and motor networks. Decreased temporal variability of dynamic functional connectivity was observed in the executive and default mode networks among left pontine infarction patients. Furthermore, abnormalities in static and dynamic functional connectivity within the executive network correlated with motor and working memory performance in patients. These findings suggest that alterations in cerebellar-cerebral static and dynamic functional connectivity could underpin the behavioral dysfunctions observed in acute pontine infarction patients.


Subject(s)
Brain Stem Infarctions , Cerebellum , Magnetic Resonance Imaging , Neural Pathways , Pons , Humans , Male , Female , Middle Aged , Cerebellum/physiopathology , Cerebellum/diagnostic imaging , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging , Pons/diagnostic imaging , Pons/physiopathology , Brain Stem Infarctions/physiopathology , Brain Stem Infarctions/diagnostic imaging , Aged , Adult , Cerebral Cortex/physiopathology , Cerebral Cortex/diagnostic imaging , Nerve Net/physiopathology , Nerve Net/diagnostic imaging
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