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Human Brain Mapping Oct 2023Behavioral variant frontotemporal dementia is characterized by heterogeneous frontal, insular, and anterior temporal atrophy patterns that vary along left-right and...
Behavioral variant frontotemporal dementia is characterized by heterogeneous frontal, insular, and anterior temporal atrophy patterns that vary along left-right and dorso-ventral axes. Little is known about how these structural imbalances impact clinical symptomatology. The goal of this study was to assess the frequency of frontotemporal asymmetry (right- or left-lateralization) and dorsality (ventral or dorsal predominance of atrophy) and to investigate their clinical correlates. Neuropsychiatric symptoms and structural images were analyzed for 250 patients with behavioral variant frontotemporal dementia. Frontotemporal atrophy was most often symmetric while left-lateralized (9%) and right-lateralized (17%) atrophy were present in a minority of patients. Atrophy was more often ventral (32%) than dorsal (3%) predominant. Patients with right-lateralized atrophy were characterized by higher severity of abnormal eating behavior and hallucinations compared to those with left-lateralized atrophy. Subsequent analyses clarified that eating behavior was associated with right atrophy to a greater extent than a lack of left atrophy, and hallucinations were driven mainly by right atrophy. Dorsality analyses showed that anxiety, euphoria, and disinhibition correlated with ventral-predominant atrophy. Agitation, irritability, and depression showed greater severity with a lack of regional atrophy, including in dorsal regions. Aberrant motor behavior and apathy were not explained by asymmetry or dorsality. This study provides additional insight into how anatomical heterogeneity influences the clinical presentation of patients with behavioral variant frontotemporal dementia. Behavioral symptoms can be associated not only with the presence or absence of focal atrophy, but also with right/left or dorsal/ventral imbalance of gray matter volume.
Topics: Humans; Frontotemporal Dementia; Magnetic Resonance Imaging; Apathy; Behavioral Symptoms; Hallucinations; Atrophy; Neuropsychological Tests
PubMed: 37471695
DOI: 10.1002/hbm.26428 -
Neuron Dec 2023The ability to extinguish fear responses to stimuli that no longer predict danger is critical for adaptive behavior and increases the likelihood of survival. During fear...
The ability to extinguish fear responses to stimuli that no longer predict danger is critical for adaptive behavior and increases the likelihood of survival. During fear extinction, dopamine (DA) neurons signal the absence of the expected aversive outcome, and this extinction prediction error (EPE) signal is crucial for initiating and driving extinction learning. However, the neural circuits underlying the EPE signal have remained elusive. Here, we investigate the input-output circuitry of EPE-encoding DA neurons in male mice. By employing projection-specific fiber photometry and optogenetics, we demonstrate that these neurons project to a restricted subregion of the nucleus accumbens. Comprehensive anatomical analyses, as well as projection-specific chemogenetic manipulations combined with recordings of DA biosensors, further uncover the dorsal raphe as one key input structure critical for generating the EPE signal. Together, our results reveal for the first time the functional architecture of EPE-encoding DA neurons crucial for driving fear extinction learning.
Topics: Mice; Male; Animals; Dopaminergic Neurons; Extinction, Psychological; Fear; Learning; Nucleus Accumbens; Ventral Tegmental Area
PubMed: 37741275
DOI: 10.1016/j.neuron.2023.08.025 -
Developmental Cognitive Neuroscience Dec 2023Hemispherectomy is a surgical procedure in which an entire hemisphere of a patient's brain is resected or functionally disconnected to manage seizures in individuals...
Hemispherectomy is a surgical procedure in which an entire hemisphere of a patient's brain is resected or functionally disconnected to manage seizures in individuals with drug-resistant epilepsy. Despite the extensive loss of both ventral and dorsal visual pathways in one hemisphere, pediatric patients who have undergone hemispherectomy show a remarkably high degree of perceptual function across many domains. In the current study, we sought to understand the extent to which functions of the ventral and dorsal visual pathways reorganize to the contralateral hemisphere following childhood hemispherectomy. To this end, we collected fMRI data from an equal number of left and right hemispherectomy patients who completed tasks that typically elicit lateralized responses from the ventral or the dorsal pathway, namely, word (left ventral), face (right ventral), tool (left dorsal), and global form (right dorsal) perception. Overall, there was greater evidence of functional reorganization in the ventral pathway than in the dorsal pathway. Importantly, because ventral and dorsal reorganization was tested within the very same patients, these results cannot be explained by idiosyncratic factors such as disease etiology, age at the time of surgery, or age at testing. These findings suggest that because the dorsal pathway may mature earlier, it may have a shorter developmental window of plasticity than the ventral pathway and, hence, be less malleable after perturbation.
Topics: Humans; Child; Hemispherectomy; Visual Pathways; Brain; Magnetic Resonance Imaging
PubMed: 37976921
DOI: 10.1016/j.dcn.2023.101323 -
Neuron Mar 2024To survive, animals need to balance their exploratory drive with their need for safety. Subcortical circuits play an important role in initiating and modulating movement...
To survive, animals need to balance their exploratory drive with their need for safety. Subcortical circuits play an important role in initiating and modulating movement based on external demands and the internal state of the animal; however, how motivation and onset of locomotion are regulated remain largely unresolved. Here, we show that a glutamatergic pathway from the medial septum and diagonal band of Broca (MSDB) to the ventral tegmental area (VTA) controls exploratory locomotor behavior in mice. Using a self-supervised machine learning approach, we found an overrepresentation of exploratory actions, such as sniffing, whisking, and rearing, when this projection is optogenetically activated. Mechanistically, this role relies on glutamatergic MSDB projections that monosynaptically target a subset of both glutamatergic and dopaminergic VTA neurons. Taken together, we identified a glutamatergic basal forebrain to midbrain circuit that initiates locomotor activity and contributes to the expression of exploration-associated behavior.
Topics: Mice; Animals; Ventral Tegmental Area; Exploratory Behavior; Dopaminergic Neurons; Motivation
PubMed: 38266645
DOI: 10.1016/j.neuron.2023.12.016 -
Molecular Genetics & Genomic Medicine Oct 2023Annular pancreas (AP) is a congenital defect of unknown cause in which the pancreas encircles the duodenum. Theories include abnormal migration and rotation of the...
BACKGROUND
Annular pancreas (AP) is a congenital defect of unknown cause in which the pancreas encircles the duodenum. Theories include abnormal migration and rotation of the ventral bud, persistence of ectopic pancreatic tissue, and inappropriate fusion of the ventral and dorsal buds before rotation. The few reported familial cases suggest a genetic contribution.
METHODS
We conducted exome sequencing in 115 affected infants from the California birth defects registry.
RESULTS
Seven cases had a single heterozygous missense variant in IQGAP1, five of them with CADD scores >20; seven other infants had a single heterozygous missense variant in NRCAM, five of them with CADD scores >20. We also looked at genes previously associated with AP and found two rare heterozygous missense variants, one each in PDX1 and FOXF1.
CONCLUSION
IQGAP1 and NRCAM are crucial in cell polarization and migration. Mutations result in decreased motility which could possibly cause the ventral bud to not migrate normally. To our knowledge, this is the first study reporting a possible association for IQGAP1 and NRCAM with AP. Our findings of rare genetic variants involved in cell migration in 15% of our population raise the possibility that AP may be related to abnormal cell migration.
PubMed: 37635636
DOI: 10.1002/mgg3.2233 -
BioRxiv : the Preprint Server For... Nov 2023Contextual associations are critical for survival but must be extinguished when new conditions render them nonproductive. By most accounts, extinction forms a new memory...
Contextual associations are critical for survival but must be extinguished when new conditions render them nonproductive. By most accounts, extinction forms a new memory that competes with the original association for control over behavior, but the mechanisms underlying this competition remain largely enigmatic. Here we find the retrieval of contextual fear conditioning and extinction yield contrasting patterns of activity in prefrontal cortex and ventral hippocampus. Within ventral CA1, activation of somatostatin-expressing interneurons (SST-INs) occurs preferentially during extinction retrieval and correlates with differences in input synaptic transmission. Optogenetic manipulation of these cells but not parvalbumin interneurons (PV-INs) elicits bidirectional changes in fear expression following extinction, and the ability of SST-INs to gate fear is specific to the context in which extinction was acquired. A similar pattern of results was obtained following reward-based extinction. These data show that ventral hippocampal SST-INs are critical for extinguishing prior associations and thereby gate relapse of both aversive and appetitive responses.
PubMed: 38077077
DOI: 10.1101/2023.11.28.568835 -
Journal of Clinical Medicine May 2024Abdominal wall reconstruction is a common and necessary surgery, two factors that drive innovation. This review article examines recent developments in ventral hernia... (Review)
Review
Abdominal wall reconstruction is a common and necessary surgery, two factors that drive innovation. This review article examines recent developments in ventral hernia repair including primary fascial closure, mesh selection between biologic, permanent synthetic, and biosynthetic meshes, component separation, and functional abdominal wall reconstruction from a plastic surgery perspective, exploring the full range of hernia repair's own reconstructive ladder. New materials and techniques are examined to explore the ever-increasing options available to surgeons who work within the sphere of ventral hernia repair and provide updates for evolving trends in the field.
PubMed: 38792418
DOI: 10.3390/jcm13102876 -
Neurobiology of Disease Nov 2023Parkinson's disease (PD) has been showed perfusion and neural activity alterations in specific regions, such as the motor and visual networks; however, the clinical...
Parkinson's disease (PD) has been showed perfusion and neural activity alterations in specific regions, such as the motor and visual networks; however, the clinical significance of coupling changes is still unknown. To identify how neurovascular coupling changes during the pathophysiology of PD, patients and healthy controls underwent multiparametric magnetic resonance imaging to measure neural activity organization of segregation and integration using amplitude of low-frequency fluctuation (ALFF) and functional connectivity strength (FCS), and measure vascular responses using cerebral blood flow (CBF). Neurovascular coupling was calculated as the global CBF-ALFF and CBF-FCS coupling and the regional CBF/ALFF and CBF/FCS ratio. Correlations and dynamic causal modeling was then used to evaluate relationships with disease-alterations to clinical variables and information flow. Neurovascular coupling was impaired in PD with decreased global CBF-ALFF and CBF-FCS coupling, as well as decreased CBF/ALFF in the parieto-occipital cortex (dorsal visual stream) and CBF/FCS in the temporo-occipital cortex (ventral visual stream); these decouplings were associated with motor and non-motor impairments. The distinctive patterns of neurovascular coupling alterations within the dorsal and ventral visual streams of the visual system could potentially provide additional understanding into the pathophysiological mechanisms of PD.
Topics: Humans; Neurovascular Coupling; Parkinson Disease; Cerebrovascular Circulation; Cerebral Cortex; Clinical Relevance
PubMed: 37838006
DOI: 10.1016/j.nbd.2023.106323 -
BioRxiv : the Preprint Server For... Dec 2023The movements that give rise to the body's structure are powered by cell shape changes and rearrangements that are coordinated at supracellular scales. How such cellular...
The movements that give rise to the body's structure are powered by cell shape changes and rearrangements that are coordinated at supracellular scales. How such cellular coordination arises and integrates different morphogenetic programs is unclear. Using quantitative imaging, we found a complex pattern of adherens junction (AJ) levels in the ectoderm prior to gastrulation onset in . AJ intensity exhibited a double-sided gradient, with peaks at the dorsal midline and ventral neuroectoderm. We show that this dorsal-ventral AJ pattern is regulated by epidermal growth factor (EGF) signaling and that this signal is required for ectoderm cell movement during mesoderm invagination and axis extension. We identify AJ levels and junctional actomyosin as downstream effectors of EGFR signaling. Overall, our study demonstrates a mechanism of coordination between tissue folding and convergent extension that facilitates embryo-wide gastrulation movements.
PubMed: 38187543
DOI: 10.1101/2023.12.22.573057 -
The Journal of Neuroscience : the... Dec 2023Impulsivity is a behavioral trait that is elevated in many neuropsychiatric disorders. Parkinson's disease (PD) patients can exhibit a specific pattern of reward-seeking...
Impulsivity is a behavioral trait that is elevated in many neuropsychiatric disorders. Parkinson's disease (PD) patients can exhibit a specific pattern of reward-seeking impulsive-compulsive behaviors (ICBs), as well as more subtle changes to generalized trait impulsivity. Prior studies in healthy controls (HCs) suggest that trait impulsivity is regulated by D autoreceptors in mesocorticolimbic circuits. While altered D binding is noted in ICB PD patients, there is limited prior assessment of the trait impulsivity-D relationship in PD, and no prior direct comparison with patterns in HCs. We examined 54 PD (36 M; 18 F) and 31 sex- and age-matched HC (21 M; 10 F) subjects using [F]fallypride, a high-affinity D receptor ligand, to measure striatal and extrastriatal D nondisplaceable binding potential (BP). Subcortical and cortical assessment exclusively used ROI or exploratory-voxelwise methods, respectively. All completed the Barratt Impulsiveness Scale, a measure of trait impulsivity. Subcortical ROI analyses indicated a negative relationship between trait impulsivity and D BP in the ventral striatum and amygdala of HCs but not in PD. By contrast, voxelwise methods demonstrated a positive trait impulsivity-D BP correlation in ventral frontal olfactocentric-paralimbic cortex of subjects with PD but not HCs. Subscale analysis also highlighted different aspects of impulsivity, with significant interactions between group and motor impulsivity in the ventral striatum, and attentional impulsivity in the amygdala and frontal paralimbic cortex. These results suggest that dopamine functioning in distinct regions of the mesocorticolimbic circuit influence aspects of impulsivity, with the relative importance of regional dopamine functions shifting in the neuropharmacological context of PD. The biological determinants of impulsivity have broad clinical relevance, from addiction to neurodegenerative disorders. Here, we address biomolecular distinctions in Parkinson's disease. This is the first study to evaluate a large cohort of Parkinson's disease patients and age-matched healthy controls with a measure of trait impulsivity and concurrent [F]fallypride PET, a method that allows quantification of D2/3 receptors throughout the mesocorticolimbic network. We demonstrate widespread differences in the trait impulsivity-dopamine relationship, including (1) loss of subcortical relationships present in the healthy brain and (2) emergence of a new relationship in a limbic cortical area. This illustrates the loss of mechanisms of behavioral regulation present in the healthy brain while suggesting a potential compensatory response and target for future investigation.
Topics: Humans; Dopamine; Parkinson Disease; Impulsive Behavior; Receptors, Dopamine D2; Ventral Striatum; Positron-Emission Tomography
PubMed: 37852792
DOI: 10.1523/JNEUROSCI.1037-23.2023