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Brain Communications 2020The orbitofrontal cortex in primates including humans is the key brain area in emotion, and in the representation of reward value and in non-reward, that is not... (Review)
Review
The orbitofrontal cortex in primates including humans is the key brain area in emotion, and in the representation of reward value and in non-reward, that is not obtaining an expected reward. Cortical processing before the orbitofrontal cortex is about the identity of stimuli, i.e. 'what' is present, and not about reward value. There is evidence that this holds for taste, visual, somatosensory and olfactory stimuli. The human medial orbitofrontal cortex represents many different types of reward, and the lateral orbitofrontal cortex represents non-reward and punishment. Not obtaining an expected reward can lead to sadness, and feeling depressed. The concept is advanced that an important brain region in depression is the orbitofrontal cortex, with depression related to over-responsiveness and over-connectedness of the non-reward-related lateral orbitofrontal cortex, and to under-responsiveness and under-connectivity of the reward-related medial orbitofrontal cortex. Evidence from large-scale voxel-level studies and supported by an activation study is described that provides support for this hypothesis. Increased functional connectivity of the lateral orbitofrontal cortex with brain areas that include the precuneus, posterior cingulate cortex and angular gyrus is found in patients with depression and is reduced towards the levels in controls when treated with medication. Decreased functional connectivity of the medial orbitofrontal cortex with medial temporal lobe areas involved in memory is found in patients with depression. Some treatments for depression may act by reducing activity or connectivity of the lateral orbitofrontal cortex. New treatments that increase the activity or connectivity of the medial orbitofrontal cortex may be useful for depression. These concepts, and that of increased activity in non-reward attractor networks, have potential for advancing our understanding and treatment of depression. The focus is on the orbitofrontal cortex in primates including humans, because of differences of operation of the orbitofrontal cortex, and indeed of reward systems, in rodents. Finally, the hypothesis is developed that the orbitofrontal cortex has a special role in emotion and decision-making in part because as a cortical area it can implement attractor networks useful in maintaining reward and emotional states online, and in decision-making.
PubMed: 33364600
DOI: 10.1093/braincomms/fcaa196 -
Translational Psychiatry Mar 2021Early detection of patients with late-life depression (LLD) with a high risk of developing dementia contributes to early intervention. Odor identification (OI)...
Early detection of patients with late-life depression (LLD) with a high risk of developing dementia contributes to early intervention. Odor identification (OI) dysfunction serves as a marker for predicting dementia, but whether OI dysfunction increases the risk of dementia in LLD patients remains unclear. The present study aimed to explore the interactive effect of LLD and OI dysfunction on the risk of dementia and its underlying neuroimaging changes. One hundred and fifty-seven LLD patients and 101 normal controls were recruited, and data on their OI, cognition, activity of daily living (ADL), and resting-state functional magnetic resonance imaging were collected. Two × two factorial analyses were used to analyze the interactive effects of LLD and OI dysfunction on neuropsychological and neuroimaging abnormalities. Mediation analyses were used to explore whether abnormalities detected by neuroimaging mediated the the associations between OI and cognition/ADL. The results suggested that LLD and OI dysfunction exhibited additive effects on reduced ADL, global cognition and memory scores, as well as neuroimaging variables including (i) increased fractional amplitude of low-frequency fluctuation (fALFF) in the right orbitofrontal cortex and right precentral cortex, and (ii) increased regional homogeneity (ReHo) in the left hippocampus/fusiform gyrus, etc. In addition, these increased fALFF and ReHo values were associated with reduced neuropsychological scores (ADL, global cognition, memory, and language). Moreover, ReHo of the left hippocampus/fusiform gyrus completely mediated the relationship between OI and ADL, and partially mediated the relationship between OI and global cognition. Overall, mediated by the hypersynchronization of the left hippocampus/fusiform gyrus, OI dysfunction may increase the risk of dementia in LLD patients.
Topics: Brain; Dementia; Depression; Hippocampus; Humans; Magnetic Resonance Imaging; Olfaction Disorders; Temporal Lobe
PubMed: 33731679
DOI: 10.1038/s41398-021-01291-0 -
Journal of Affective Disorders Jun 2022Odor identification (OI) impairment increases the risk of Alzheimer's disease and brain abnormalities in patients with late-life depression (LLD). However, it remains...
BACKGROUND
Odor identification (OI) impairment increases the risk of Alzheimer's disease and brain abnormalities in patients with late-life depression (LLD). However, it remains unclear whether abnormal functional connectivity (FC) of olfactory regions is involved in the relationship between OI impairment and dementia risk in LLD patients. The current study aims to explore the olfactory FC patterns of LLD patients and how olfactory FCs mediate the relationship between OI and cognition.
METHODS
A total of 150 participants underwent resting-state functional magnetic resonance imaging and psychometric and olfactory assessments. The primary and secondary olfactory regions were selected as regions of interest to investigate olfactory FC patterns and their association with OI and cognitive performance in LLD patients.
RESULTS
Compared with LLD patients without OI impairment and normal controls, LLD patients with OI impairment exhibited increased FC between the left orbital frontal cortex (OFC) and left calcarine gyrus, between the left OFC and right lingual gyrus, between the right OFC and right rectus gyrus, and decreased FC between the right piriform cortex and right superior parietal lobule. Additionally, these abnormal FCs were associated with scores of OI, global cognition and language function. Finally, the FC between the right piriform cortex and right superior parietal lobule exhibited a partially mediated effect on the relationship between OI and MMSE scores.
LIMITATIONS
The present study did not exclude the possible effect of drugs.
CONCLUSION
LLD patients with OI impairment exhibited more disrupted olfactory FC (a decrease in the primary olfactory cortex and an increase in the secondary olfactory cortex) than LLD patients with intact OI, and these abnormal FCs may serve as potential targets for neuromodulation in LLD patients to prevent them from developing dementia.
Topics: Alzheimer Disease; Depression; Humans; Magnetic Resonance Imaging; Prefrontal Cortex; Smell
PubMed: 35292309
DOI: 10.1016/j.jad.2022.03.014 -
Reviews in the Neurosciences Dec 2022There is evidence that olfactory cortex responds to its afferent input with the generation of cell assemblies: collections of principal neurons that fire together over a... (Review)
Review
There is evidence that olfactory cortex responds to its afferent input with the generation of cell assemblies: collections of principal neurons that fire together over a time scale of tens of ms. If such assemblies form an odor representation, then a fundamental question is how each assembly then induces neuronal activity in downstream structures. We have addressed this question in a detailed model of superficial layers of lateral entorhinal cortex, a recipient of input from olfactory cortex and olfactory bulb. Our results predict that the response of the fan cell subpopulation can be approximated by a relatively simple Boolean process, somewhat along the lines of the McCulloch/Pitts scheme; this is the case because of the sparsity of recurrent excitation amongst fan cells. However, because of recurrent excitatory connections between layer 2 and layer 3 pyramidal cells, synaptic and probably also gap junctional, the response of pyramidal cell subnetworks cannot be so approximated. Because of the highly structured anatomy of entorhinal output projections, our model suggests that downstream targets of entorhinal cortex (dentate gyrus, hippocampal CA3, CA1, piriform cortex, olfactory bulb) receive differentially processed information.
Topics: Humans; Entorhinal Cortex; Hippocampus; Neurons; Pyramidal Cells
PubMed: 35447022
DOI: 10.1515/revneuro-2022-0011 -
BioRxiv : the Preprint Server For... Sep 2023Schizophrenia is marked by poor social functioning that can have a severe impact on quality of life and independence, but the underlying neural circuity is not well...
Schizophrenia is marked by poor social functioning that can have a severe impact on quality of life and independence, but the underlying neural circuity is not well understood. Here we used a translational model of subanesthetic ketamine in mice to delineate neural pathways in the brain linked to social deficits in schizophrenia. Mice treated with chronic ketamine (30 mg/kg/day for 10 days) exhibit profound social and sensorimotor deficits as previously reported. Using three- dimensional c-Fos immunolabeling and volume imaging (iDISCO), we show that ketamine treatment resulted in hypoactivation of the lateral septum (LS) in response to social stimuli. Chemogenetic activation of the LS rescued social deficits after ketamine treatment, while chemogenetic inhibition of previously active populations in the LS (i.e. social engram neurons) recapitulated social deficits in ketamine-naïve mice. We then examined the translatome of LS social engram neurons and found that ketamine treatment dysregulated genes implicated in neuronal excitability and apoptosis, which may contribute to LS hypoactivation. We also identified 38 differentially expressed genes (DEGs) in common with human schizophrenia, including those involved in mitochondrial function, apoptosis, and neuroinflammatory pathways. Chemogenetic activation of LS social engram neurons induced downstream activity in the ventral part of the basolateral amygdala, subparafascicular nucleus of the thalamus, intercalated amygdalar nucleus, olfactory areas, and dentate gyrus, and it also reduces connectivity of the LS with the piriform cortex and caudate-putamen. In sum, schizophrenia-like social deficits may emerge via changes in the intrinsic excitability of a discrete subpopulation of LS neurons that serve as a central hub to coordinate social behavior via downstream projections to reward, fear extinction, motor and sensory processing regions of the brain.
PubMed: 37609170
DOI: 10.1101/2023.08.08.552372 -
Neural Regeneration Research Jan 2024Adult neurogenesis, the process of creating new neurons, involves the coordinated division, migration, and differentiation of neural stem cells. This process is... (Review)
Review
Adult neurogenesis, the process of creating new neurons, involves the coordinated division, migration, and differentiation of neural stem cells. This process is restricted to neurogenic niches located in two distinct areas of the brain: the subgranular zone of the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricle, where new neurons are generated and then migrate to the olfactory bulb. Neurogenesis has been thought to occur only during the embryonic and early postnatal stages and to decline with age due to a continuous depletion of neural stem cells. Interestingly, recent years have seen tremendous progress in our understanding of adult brain neurogenesis, bridging the knowledge gap between embryonic and adult neurogenesis. Here, we discuss the current status of adult brain neurogenesis in light of what we know about neural stem cells. In this notion, we talk about the importance of intracellular signaling molecules in mobilizing endogenous neural stem cell proliferation. Based on the current understanding, we can declare that these molecules play a role in targeting neurogenesis in the mature brain. However, to achieve this goal, we need to avoid the undesired proliferation of neural stem cells by controlling the necessary checkpoints, which can lead to tumorigenesis and prove to be a curse instead of a blessing or hope.
PubMed: 37488837
DOI: 10.4103/1673-5374.375317 -
PeerJ 2020Altered cerebral blood flow (CBF) and amplitude of low-frequency fluctuation (ALFF) have been reported in hemodialysis patients. However, neurovascular coupling...
BACKGROUND
Altered cerebral blood flow (CBF) and amplitude of low-frequency fluctuation (ALFF) have been reported in hemodialysis patients. However, neurovascular coupling impairments, which provide a novel insight into the human brain, have not been reported in hemodialysis patients.
METHODS
We combined arterial spin labeling (ASL) and blood oxygen level dependent (BOLD) techniques to investigate neurovascular coupling alterations and its relationships with demographic and clinical data in 46 hemodialysis patients and 47 healthy controls. To explore regional neuronal activity, ALFF was obtained from resting-state functional MRI. To measure cerebral vascular response, CBF was calculated from ASL. The across-voxel CBF-ALFF correlations for global neurovascular coupling and CBF/ALFF ratio for regional neurovascular coupling were compared between hemodialysis patients and healthy controls. Two-sample -tests were used to compare the intergroup differences in CBF and ALFF. Multiple comparisons were corrected using a voxel-wise false discovery rate (FDR) method ( < 0.05).
RESULTS
All hemodialysis patients and healthy controls showed significant across-voxel correlations between CBF and ALFF. Hemodialysis patients showed a significantly reduced global CBF-ALFF coupling ( = 0.0011) compared to healthy controls at the voxel-level. Of note, decreased CBF/ALFF ratio was exclusively located in the bilateral amygdala involved in emotional regulation and cognitive processing in hemodialysis patients. In hemodialysis patients, the decreased CBF (right olfactory cortex, anterior cingulate gyrus and bilateral insula) and ALFF (bilateral precuneus and superior frontal gyrus) were mainly located in the default mode network and salience network-related regions as well as increased CBF in the bilateral thalamus.
CONCLUSIONS
These novel findings reveal that disrupted neurovascular coupling may be a potential neural mechanism in hemodialysis patients.
PubMed: 32328355
DOI: 10.7717/peerj.8989 -
Scientific Reports Aug 2021Removing function from a developed and functional sensory system is known to alter both cerebral morphology and functional connections. To date, a majority of studies...
Removing function from a developed and functional sensory system is known to alter both cerebral morphology and functional connections. To date, a majority of studies assessing sensory-dependent plasticity have focused on effects from either early onset or long-term sensory loss and little is known how the recent sensory loss affects the human brain. With the aim of determining how recent sensory loss affects cerebral morphology and functional connectivity, we assessed differences between individuals with acquired olfactory loss (duration 7-36 months) and matched healthy controls in their grey matter volume, using multivariate pattern analyses, and functional connectivity, using dynamic connectivity analyses, within and from the olfactory cortex. Our results demonstrate that acquired olfactory loss is associated with altered grey matter volume in, among others, posterior piriform cortex, a core olfactory processing area, as well as the inferior frontal gyrus and angular gyrus. In addition, compared to controls, individuals with acquired anosmia displayed significantly stronger dynamic functional connectivity from the posterior piriform cortex to, among others, the angular gyrus, a known multisensory integration area. When assessing differences in dynamic functional connectivity from the angular gyrus, individuals with acquired anosmia had stronger connectivity from the angular gyrus to areas primary responsible for basic visual processing. These results demonstrate that recently acquired sensory loss is associated with both changed cerebral morphology within core olfactory areas and increase dynamic functional connectivity from olfactory cortex to cerebral areas processing multisensory integration.
Topics: Aged; Anosmia; Brain; Brain Mapping; Case-Control Studies; Female; Gray Matter; Humans; Male; Middle Aged; Support Vector Machine
PubMed: 34385571
DOI: 10.1038/s41598-021-95968-7 -
Acta Radiologica (Stockholm, Sweden :... Sep 2023Bipolar disorder (BD) is a mental health disorder.
BACKGROUND
Bipolar disorder (BD) is a mental health disorder.
PURPOSE
To investigate the peripheric and central olfactory measurements in patients with BD using magnetic resonance imaging (MRI).
MATERIAL AND METHODS
This study was conducted retrospectively. Group 1 consisted of 27 euthymic patients with BD (14 men, 13 women) and Group 2 consisted of 27 healthy controls (14 men, 13 women). Olfactory bulb (OB) volume and olfactory sulcus (OS) depth (peripheric), and corpus amygdala and insular gyrus area (central) measurements were performed using cranial MRI.
RESULTS
OB volume and OS depth value of the bipolar group were lower than the control group, but there were no significant differences between the groups ( > 0.05). The corpus amygdala and left insular gyrus area of the bipolar group were significantly lower than those in the control group ( < 0.05). There were positive correlations between OB volumes and OS depths, the insular gyrus areas, and the corpus amygdala areas ( < 0.05). As the number of depressive episodes and duration of illness increased in bipolar patients, the depth of the sulcus decreased ( < 0.05).
CONCLUSION
In the present study a correlation was detected between OB volumes and the structures, known as emotional processing (e.g. insular gyrus area, corpus amygdala), and clinical features. Accordingly, new treatment techniques, such as olfactory training, may be considered an option in the treatment of such patients with BD.
Topics: Male; Humans; Female; Bipolar Disorder; Olfaction Disorders; Retrospective Studies; Smell; Amygdala; Magnetic Resonance Imaging
PubMed: 37312533
DOI: 10.1177/02841851231179174 -
The Journal of Clinical Endocrinology... Feb 2024To investigate the brain structural and functional alterations in patients with thyroid-associated ophthalmopathy (TAO) before and after glucocorticoid therapy, using...
OBJECTIVE
To investigate the brain structural and functional alterations in patients with thyroid-associated ophthalmopathy (TAO) before and after glucocorticoid therapy, using voxel-based morphometry (VBM) as well as resting-state functional magnetic resonance imaging (MRI) with amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo).
METHODS
Between 2019 and 2022, 32 patients with TAO and 23 healthy controls underwent pre-therapy MRI in Nanjing, China. Intravenous glucocorticoid therapy was administered to all patients. At 3 months after end of therapy, 26 patients were available for rescanned MRI. VBM, ALFF, and ReHo were used to evaluate the brain structural and functional differences.
RESULTS
Before therapy, TAO patients showed significantly decreased gray matter volume (GMV) in the left orbital part of superior frontal gyrus (ORBsup) and medial superior frontal gyrus (SFGmed) than healthy controls. Patients had higher ALFF values in bilateral gyrus rectus and olfactory cortex and lower values in bilateral cuneus. Patients also showed decreased ReHo values in bilateral lingual gyrus. After therapy, increased GMV in the left anterior cingulate gyrus and SFGmed, increased ALFF values in bilateral cuneus and superior occipital gyrus, and increased ReHo values in bilateral SFGmed were found in TAO patients compared to the pre-therapy cohort. Compared to controls, decreased GMV in left ORBsup was observed in post-therapy TAO patients.
CONCLUSION
Our results indicated that TAO might cause functional and structural deficits in the visual and emotional regions of the brain, with recovery in the former and partial restoration in the latter after effective glucocorticoid therapy. These findings may lead to deeper understanding of the pathophysiological mechanism behind TAO.
Topics: Humans; Glucocorticoids; Graves Ophthalmopathy; Brain; Gray Matter; Brain Mapping; Magnetic Resonance Imaging
PubMed: 37864850
DOI: 10.1210/clinem/dgad626