Parietal Cortex Research Articles

Combination of low-dose, long-term immunoglobulin and mirtazapine is effective in progressive multifocal leukoencephalopathy caused by JC virus infection

BackgroundProgressive multifocal leukoencephalopathy (PML) is an often fatal disease of the central nervous system caused by opportunistic infection of John Cunningham Polyomavirus (JCV). There’s still no antiviral therapeutic strategy which was generally recognized as effective. The prognosis may differ in patients with different pathological mechanisms and treatments. We aim to report the effectiveness of combined treatment of low-dose, long-term immunoglobulin and mirtazapine in a pathologically proved PML case.Case presentationA patient presented with progressive acalculia, right-left confusion and visual neglection was recorded. She received 10-year immunosuppressive therapy for dermatomyositis. White matter lesions located in bilateral parietal lobe and callosum area symmetrically in MR scanning. JC virus analysis and brain biopsy in left parietal lobe were performed. The number of JCV copies was 2595 in CSF and 282,809 in brain specimen. Abundant foamy macrophages and the lymphatic cells were obvious in immunohistochemistry staining. Few SV-40 positive JC infected cell and more CD4 + and CD68 + cells were predominant. Immunosuppressive drugs were terminated after being diagnosed as PML for positive JCV and pathological characteristics. In addition, immunoglobulin (5 g/day) and mirtazapine (45 mg/day) were used. JC virus in CSF decreased to 0 after treatment for 4 months and was still negative in June 2023. The clinical symptoms improved, and white matter lesions recovered significantly.ConclusionsWe demonstrated that the combination treatment of IVIG and mirtazapine was effective in PML. Low-dose, long-term immunoglobulin might regulate the immune status in our case with controlled inflammatory reaction instead of destructive virus spreading. The therapy may be a prospective option for PML.

White matter alterations associated with chronic cannabis use disorder: a structural network and fixel-based analysis

Cannabis use disorder (CUD) is associated with adverse mental health effects, as well as social and cognitive impairment. Given prevalence rates of CUD are increasing, there is considerable efforts, and need, to identify prognostic markers which may aid in minimising any harm associated with this condition. Previous neuroimaging studies have revealed changes in white matter (WM) organization in people with CUD, though, the findings are mixed. In this study, we applied MRI-based analysis techniques that offer complimentary mechanistic insights, i.e., a connectome approach and fixel-based analysis (FBA) to investigate properties of individual WM fibre populations and their microstructure across the entire brain, providing a highly sensitive approach to detect subtle changes and overcome limitations of previous diffusion models. We compared 56 individuals with CUD (median age 25 years) to a sample of 38 healthy individuals (median age 31.5 years). Compared to controls, those with CUD had significantly increased structural connectivity strength (FDR corrected) across 9 edges between the right parietal cortex and several cortical and subcortical regions, including left orbitofrontal, left temporal pole, and left hippocampus and putamen. Utilizing FBA, WM density was significantly higher in those with CUD (FWE-corrected) across the splenium of the corpus callosum, and lower in the bilateral cingulum and right cerebellum. We observed significant correlation between cannabis use over the past month and connectivity strength of the frontoparietal edge, and between age of regular use and WM density of the bilateral cingulum and right cerebellum. Our findings enhance the understanding of WM architecture alterations associated with CUD.

Comparing Brain Activation Patterns in Stress-Induced and Post-Stress Recovery States of Highly and Moderately Stressed Individuals

Our study aimed to identify the mechanisms of stress-induced and post-stress recovery states by evaluating voxel type and the total number of voxels activated based on Perceived Stress Scale scores. Functional MRI (fMRI) was used to measure the brain activation patterns in participants grouped into moderate- and high-stress categories. The number of activation voxels in the parahippocampal gyrus of the limbic lobe was greater in the high-stress group than in the moderate-stress group. Moreover, only the high-stress group showed the characteristic activation of the left precuneus. The moderate-stress group showed a greater number of activation voxels than the high-stress group for the occipital, frontal, and limbic lobes, while the reverse was true for the parietal lobe. In the post-stress recovery phase, the left lingual, inferior frontal, and middle frontal gyri were activated, and the number of activation voxels in these areas was greater in the high-stress group than in the moderate-stress group. The characteristic activation of the declive in the left cerebellum was observed in the moderate-stress group, whereas the activation of the right cuneus was dominant in the high-stress group. Our findings suggest that perceived stress may play an important role in determining the neural mechanisms underlying stress and post-stress recovery, providing insights into the complex interplay between the psychological and neural processes occurring in response to stress.

The value of amide proton transfer imaging in assessing brain damage in patients with obstructive sleep apnea

ObjectiveTo investigate the application value of amide proton transfer (APT) magnetic resonance imaging in evaluating brain damage in patients with obstructive sleep apnea (OSA). Materials and methods49 OSA patients and 25 healthy individuals matched for age and sex were included as case and control groups. All study participants underwent conventional 3D T1WI and APT imaging of the head. The APT values were measured in each of the brain regions of interest (ROI). To compare the differences in APT values of each brain region between the case and control groups, to compare the differences in the efficacy of APT values of each brain region in diagnosing OSA, and to investigate the correlation between APT values of each brain region and Apnea Hypopnea Index (AHI) and minimum blood oxygen saturation. ResultsCompared to the control group, patients with OSA had elevated APT values in several brain regions (P < 0.05), and the diagnostic efficacy of the combined diagnosis of OSA by multiple brain regions is better than that by each brain region alone.Left frontal APT values were positively correlated with AHI in the case group (r = 0.33, P = 0.020).In the case group, the APT values of bilateral frontal lobe, parietal lobe, occipital lobe, left temporal lobe, right thalamus, left internal capsule, left lenticular nucleus, right cerebellar hemisphere and splenium of corpus callosum were negatively correlated with the minimum blood oxygen saturation, and the APT values for each of the above ROIs were positively correlated. ConclusionAPT imaging has a certain value in evaluating brain damage in OSA patients, which may provide a new objective imaging basis for the clinical diagnosis of OSA.

EEG synchronization patterns during a Go/No-Go task in individuals with aphasia in subacute and chronic phases of stroke

Stroke and subsequent neuroregenerative processes cause changes in neural organization of attentional functions. In this study, we attempted to identify differences in neural synchronization patterns during a visual Go/No-Go task in people with post-stroke aphasia in both subacute and chronic stroke phases. To identify neuronal underpinnings of the behavioral differences we investigated pairwise connectivity patterns using corrected imaginary phase locking value and graph-theoretic measures (efficiency, modularity and clustering coefficient) at global and local level in subacute (n = 13) and chronic stroke phases (n = 14) during a Go/No-Go task. We observed significantly lower phase synchronization in the Subacute Group in the alpha band in the connections spanning frontal and central areas of both hemispheres alongside lower local efficiency and clustering coefficient in the left frontal region. Additionally, we observed higher modularity in the beta band in the unaffected right parietal region in the Subacute Group which may denote inhibition of motor and attention functions. Those mechanisms could serve to align cognitive abilities between the damaged and healthy hemispheres, harmonizing the activity of the neuronal networks of both hemispheres disrupted by the effects of the stroke. Our findings have potential implications for rehabilitation therapies, which should take into account the pattern of connectivity changes during different phases of reovery.

Correlates and Brain Substrates of Happiness in Community-Dwelling Older Adults in India.

Happiness has been shown to influence many health-related outcomes in older adults. Identifying correlates and brain substrates of happiness across countries and cultures is an important goal, as the global older adult population continues to increase. We used univariate and multiple regression to examine associations between happiness and several demographic, health, and lifestyle variables in 665 older adults (39% female) from Kerala, India. We also used Bayesian regression to examine associations between cortical thickness and happiness in a sub-sample of 188 participants that completed MRI scanning. Happiness was significantly associated with several variables. In our multiple regression model, which included all significant univariate predictors, self-rated health, depression, anxiety, apathy, social network size, social network diversity, and social support significantly predicted happiness. Demographic indicators (age, sex, education, marital status, residence, and employment status/type), cognitive impairment, comorbidities, and leisure activities were not significantly associated with happiness in the multiple regression model. Cortical thickness in several brain regions was positively associated with happiness scores, including frontal, temporal, parietal, occipital, and cingulate regions. Understanding the key correlates is critical for identifying both modifiable factors that can be targeted in well-being interventions and fixed characteristics that identify those at-risk for reduced happiness. The widespread pattern of brain regions associated with happiness is consistent with the multifactorial nature of happiness and, given that the regions identified do not overlap with those vulnerable to cortical thinning, can help explain why subjective well-being, unlike other cognitive functions, is largely resistant to age-related decline.

Effects of traffic noise on the psychophysiological responses of college students: An EEG study

Traffic noise harms public health, but the specific mechanisms are not fully understood. To understand how traffic noise at different sound pressure levels (SPLs) affects psychophysiological responses, this study examined five SPLs of traffic noise: 40, 45, 50, 55, and 60 dB. 38 young college students were recruited for Profile of Mood States (POMS) evaluations and measurements of electrocardiogram and electroencephalogram. The study found that traffic noise exposure led to a 0.95–1.64-fold increase in mood disturbance compared to no sound, with 60 dB traffic noise causing a significantly greater increase compared to other SPLs. As SPL increased, ΔLF/HF increased by 0.01–0.83, indicating heightened stress levels. Traffic noise also induced stress responses in the brain, with α power reduced by 13.08–24.15 % compared to no sound. High SPL traffic noise significantly harmed brain comfort. Compared to 40–45 dB, exposure to 50–60 dB traffic noise significantly increased α power by 28.66–85.80 % (p < 0.05). Additionally, 60 dB traffic noise increased the likelihood of supercritical brain activity by 32.49 % compared to no sound. Psychological response changes were closely related to physiological response changes. Δα power, particularly in the frontal and parietal lobes, was the strongest predictor of the increase in total mood disturbance, suggesting these lobes should be the focus of future traffic noise-brain studies. The study emphasizes the need for a comprehensive evaluation of the negative effects of traffic noise from a psychophysiological perspective, highlighting the harm of high SPLs. The findings provide valuable insights for developing indoor acoustic environment standards.

Spike-based computational primitives to reproduce neural dynamics in the parietal cortex during motor preparation

Abstract Biologically plausible spiking neural network models of sensory cortices can be instrumental in understanding and validating their principles of computation.&amp;#xD; Models based on Cortical Computational Primitives (CCPs), such as Hebbian plasticity and Winner-Take-All (WTA) networks, have already been successful in this approach.&amp;#xD; However, the specific nature and roles of CCPs in sensorimotor cortices during cognitive tasks are yet to be fully deciphered.&amp;#xD; The evolution of motor intention in the Posterior Parietal Cortex (PPC) before arm-reaching movements is a well-suited cognitive process to assess the effectiveness of different CCPs.&amp;#xD; To this end, we propose a biologically plausible model composed of heterogeneous spiking neurons which implements and combines multiple CCPs, such as multi-timescale learning and soft WTA modules.&amp;#xD; By training the model to replicate the dynamics of in-vivo recordings from non-human primates, we show how it is effective in generating meaningful representations from unbalanced input data, and in faithfully reproducing the transition from motor planning to action selection.&amp;#xD; Our findings elucidate the importance of distributing spike-based plasticity across multi-timescales, and provide an explanation for the role of different CCPs in models of frontoparietal cortical networks for performing multisensory integration to efficiently inform action execution.&amp;#xD;

Distinct effects of slow and fast theta tACS in enhancing temporal memory

Abstract Temporal memory plays a crucial role in organizing real-life events into meaningful segments. Previous research suggests that the clustering of temporally related information builds on the neural correlates of associative memory, including theta oscillations. Transcranial alternating current stimulation (tACS) provides a means of modulating theta oscillations within associative memory networks, possibly including hippocampal modulation when targeting parietal cortex. Theta oscillations are not limited to a single frequency range, but instead, exhibit functional specialization, with slow theta (3 Hz) implicated in short-term episodic memory formation and fast theta (8 Hz) involved in spatial navigation. This study aimed to investigate the distinct effects of slow and fast theta stimulation on temporal memory. Participants encoded visual objects paired with frame color while receiving tACS stimulation at 8 Hz, 3 Hz, or sham targeting the left parietal cortex. The frame color would change for every eight objects, establishing a context boundary with each color change. Subsequently, participants performed a timeline task to assess temporal memory performance. Results showed that slow, but not fast, theta stimulation led to an enhancement in temporal accuracy (absolute temporal error) compared to sham tACS, in support of our main hypothesis. Under sham stimulation, participants consistently underestimated the temporal position of items presented further away from boundary, compared to those presented at boundary. This finding resembled temporal compression observed during event segmentation. Interestingly, fast, but not slow, theta stimulation reduced this temporal bias (rated position— actual position). This study represents the first tACS evidence for differential contributions of slow versus fast theta to temporal memory formation in humans. We speculate that parietal theta tACS may modulate the hippocampus and facilitate temporal memory formation.

Biological Methods for Diagnosing Depressive Symptoms in Patients with Schizophrenia: A Narrative Review.

Depressive symptoms in patients with schizophrenia lead to more frequent exacerbations of the underlying disease, worsen the prognosis, and increase the risk of suicide. Clinical practitioners continue to face challenges in diagnosing this disorder. This study aims to analyze published material on biological markers of depressive symptoms in patients with schizophrenia. The search of literature was conducted using the following electronic search engines (the total number of relevant papers found is also specified): ACCESSSS (n=150), Cochrane Library (n=48), PubMed (n=623), eLIBRARY (n=216), and Google Scholar (n=367). The final discussion included 67 papers consistent with the study aim and were published between January 1, 2018 and December 31, 2023. Based on the available scaterred data, it appears that plasma biomarkers (e.g. C-reactive protein, metabolic parameters, hormones, enzymes, neurotrophic factors) are limited in specificity when it comes to diagnosing depressive symptoms in schizophrenia. Our analysis of the neuroimaging findings showed that depressive manifestations are associated with a decrease in the volume of the gray matter in the parietal, frontal, and temporal lobes (particularly in Broca's and Wernicke's areas) and in specific regions of the prefrontal cortex (including the medial right superior frontal, medial orbitofrontal, and superior and middle frontal gyri). It has been suggested that the SIRT1, OXT, CDKAL1, and APOE genes are involved in the development of depressive symptoms in patients with schizophrenia. Understanding and identifying depressive symptoms in schizophrenia will improve the quality of care for patients with this disorder.

Assessing the consistency and sensitivity of the neural correlates of narrative stimuli using functional near-infrared spectroscopy

Abstract Investigating how the brain responds to rich and complex narratives, such as engaging movies, has helped researchers study higher-order cognition in 'real-world' scenarios. These neural correlates are particularly useful in populations where behavioural evidence of cognition alone is inadequate, such as children and certain patient populations. While this research has been primarily conducted in fMRI and EEG, whether functional near-infrared spectroscopy (fNIRS) can reliably detect these neural correlates at an individual level, which is required for effective use in these populations, has yet to be established. This study replicated widespread inter-subject correlations (ISCs) in the frontal, parietal and temporal cortices in fNIRS in healthy participants when they watched part of the TV episode Bang! You're Dead and listened to an audio clip from the movie Taken. Conversely, these ISCs were primarily restricted to temporal cortices when participants viewed scrambled versions of those clips. To assess whether these results were reliable at the single-participant level, two follow-up analyses were conducted. First, the consistency analysis compared each participant's ISCs against group results that excluded that individual. This approach found that 24/26 participants in Bang! You're Dead and 20/26 participants in Taken were statistically similar to the group. Second, the sensitivity analysis measured whether machine learning algorithms could decode between intact conditions and their scrambled counterparts. This approach yielded balanced accuracy scores of 81% in Bang! You're Dead and 79% in Taken. Overall, the neural correlates of narrative stimuli, as assessed by fNIRS, are reproducible across participants, supporting its broad application to clinical and developmental populations.

Detecting Amyloid Positivity Using Morphometric Magnetic ResonanceImaging.

Early detection of amyloid-β (Aβ) positivity is essential for an accurate diagnosis and treatment of Alzheimer's disease (AD), but it is currently costly and/or invasive. We aimed to classify Aβ positivity (Aβ+) using morphometric features from magnetic resonance imaging (MRI), a more accessible and non-invasive technique, in two clinical population scenarios: one containing AD, mild cognitive impairment (MCI) and cognitively normal (CN) subjects, and another only cognitively impaired subjects (AD and MCI). Demographic, cognitive (Mini-Mental State Examination [MMSE] scores), regional morphometry MRI (volumes, areas, and thicknesses), and derived morphometric graph theory (GT) features from all subjects (302 Aβ+, age: 73.3±7.2, 150 male; 246 Aβ-, age: 71.1±7.1, 131 male) were combined in different feature sets. We implemented a machine learning workflow to find the best Aβ+ classification model. In an AD+MCI+CN population scenario, the best-performing model selected 120 features (107 GT features, 12 regional morphometric features and the MMSE total score) and achieved a negative predictive value (NPVadj) of 68.4%, and a balanced accuracy (BAC) of 66.9%. In a AD+MCI scenario, the best model obtained NPVadj of 71.6%, and BAC of 70.7%, using 180 regional morphometric features (98 volumes, 52 areas and 29 thicknesses from temporal, parietal, and frontal brain regions). Although with currently limited clinical applicability, regional MRI morphometric features have clinical usefulness potential for detecting Aβ status, which may be augmented by a combination with cognitive data when cognitively normal subjects make up a substantial part of the population presenting for diagnosis.

Distinct patterns of white matter hyperintensity and cortical thickness of CSF1R-related leukoencephalopathy compared with subcortical ischemic vascular dementia.

CSF1R-related leukoencephalopathy is a type of autosomal dominant leukodystrophy caused by mutations in the colony stimulating factor 1 receptor (CSF1R) gene. Subcortical ischemic vascular dementia (SIVaD), which is caused by cerebral small vessel disease, is similar to CSF1R-related leukoencephalopathy in that it mainly affects subcortical white matter. In this study, we compared the patterns of white matter hyperintensity (WMH) and cortical thickness in CSF1R-related leukoencephalopathy with those in SIVaD. Fourteen patients with CSF1R-related leukoencephalopathy and 129 with SIVaD were retrospectively recruited from three tertiary medical centers. We extracted and visualized WMH data using voxel-based morphometry to compare the WMH distributions between the two groups. Cortical thickness was measured using a surface-based method. Statistical maps of differences in cortical thickness between the two groups were generated using a surface model, with age, sex, education, and intracranial volume as covariates. Predominant distribution of WMH in the CSF1R-related leukoencephalopathy group was in the bilateral frontal and parietal areas, whereas the SIVaD group showed diffuse WMH involvement in the bilateral frontal, parietal, and temporal areas. Compared with the SIVaD group, the CSF1R-related leukoencephalopathy group showed more severe corpus callosum atrophy (CCA) and widespread cortical thinning. To our knowledge, this is the first study using the automated MR measurement to capture WMH, cortical thinning, and CCA with signal changes in CSF1R-related leukoencephalopathy. It provides new evidence regarding differences in the patterns of WMH distribution and cortical thinning between CSF1R-related leukoencephalopathy and SIVaD.

Structural disruption in subjective cognitive decline and mild cognitive impairment.

Subjective cognitive decline (SCD) marks the initial stage in Alzheimer's disease continuum. Nonetheless, current research findings regarding brain structural changes in the SCD are inconsistent. In this study, 37 SCD patients, 28 mild cognitive impairment (MCI) patients, and 42 healthy controls (HC) were recruited to investigate structural alterations. Morphological and microstructural differences among the three groups were analyzed based on T1- and diffusion-weighted images, correlating them with neuropsychological assessments. Additionally, classification analysis was performed by using support vector machines (SVM) categorize participants into three groups based on MRI features. Both SCD and MCI showed decreased volume in left inferior parietal lobe (IPL) compared to HC, while SCD showed altered morphologies in the right inferior temporal gyrus (ITG), right insula and right amygdala, and microstructures in fiber tracts of the right ITG, lateral occipital cortex (LOC) and insula relative to MCI. Moreover, the volume in the left IPL, right LOC, right amygdala and diffusivity value in fiber tracts of right LOC were significantly correlated with cognitive functions across all subjects. The classification models achieved an accuracy of > 0.7 (AUC = 0.8) in distinguishing the three groups. Our findings suggest that SCD and MCI share similar atrophy in the IPL but show more differences in morphological and microstructural features of cortical-subcortical areas.

Galantamine combined with cognitive rehabilitation on post-stroke cognitive impairment: a proof-of-concept study

ABSTRACT Purpose We conducted a proof-of-concept study to evaluate the effects of galantamine treatment versus placebo combined to cognitive rehabilitation (CR) after stroke. Materials and methods In this 12-week, double blinded, randomized, controlled trial, patients were assigned to either combined approach of galantamine and CR (G-CR) or placebo and CR (P-CR). Primary outcome was the proportion of patients who crossed over from vascular cognitive disorder (VCD) to no-VCD at 12 weeks. Secondary outcomes included changes in cognition, mood, quality of life and the N-back fMRI paradigm, assessed at baseline, 6 and 12 weeks and after an 8-week washout period. Results Ten patients were allocated to G-RC group, 12 to the P-RC group. After 12 weeks, 40.1% of all patients converted to no-VCD with similar proportions between groups. Both groups showed improvements in episodic and working memory, executive and quality of life after 6 weeks of CR. Decreased depression and anxiety were noted, and all benefits persisted after the washout period. An interaction effect was observed in the right parietal lobule during the N-back task. Conclusions Interventions lead to improved cognition and distinct cortical reorganization without being able to establish correlation between neural changes and behavioral measures.

7422 Adipsic Diabetes Insipidus Following Pituitary Macroadenoma Resection

Abstract Disclosure: J. Chippior: None. L. Ghalib: None. A 44 year-old female with a PMH of primary hypothyroidism, and a pituitary macroadenoma that was lost to follow up, presented to the ED with a chief complaint of an acute headache and decreased visual acuity involving the right eye over the past year. Patient was found to have a large, homogenous suprasellar mass with the largest dimension measuring 6.3 cm in size, and causing displacement of the optic chiasm. Initial hormonal workup was most notable for elevated prolactin at 128 ng/ml (3.3-26.7 ng/ml), which was slightly lower than when it was previously measured 10 years ago. The patient was taken to the OR for transsphenoidal endoscopic partial resection, but within 24 hours of post-op, she developed hypernatremia at 153 mmol/dL (135-145 mmol/dL) that was suspected to be secondary to diabetes insipidus (DI). In addition, she also suffered several small strokes involving her right midbrain and basal ganglia. She required multiple doses of DDAVP throughout her stay and this was ultimately continued upon discharge. Unfortunately, as follow up MRI had shown residual tumor within the third ventricle, she returned for a 2nd resection but once again suffered additional post-operative complications. The patient experienced additional strokes involving the right frontal and parietal lobes, and her DI became more labile than before, with her serum sodium peaking at 172 mmol/dL. Despite such a high degree of hypernatremia, she did not demonstrate any signs of thirst or any desire to access free water, even after her post-stroke encephalopathy had largely resolved. With less than 100 severe cases documented over the past four decades, it was suspected that the patient had a rare form of DI known as “adipsic DI”. Osmoreceptors within the hypothalamus can trigger the release of ADH or stimulate thirst, with the former requiring a smaller change in serum osmolality to generate such a response. Pituitary surgery involves manipulation of the infundibulum and any inadvertent severing can prevent ADH’s ability to travel from the hypothalamus to the posterior pituitary, subsequently leading to DI. The majority of patients with post-op DI increase their free water intake and subsequently do not develop hypernatremia. Those with adipsic DI lack this compensatory mechanism which leads to the electrolyte disturbance, and carries a higher risk of morbidity and mortality than those with typical DI. Following her second surgery, our patient was discharged with DDAVP once again but this time with a higher dose and frequency. She’s had numerous hospital readmissions since then for altered mental status in the setting of hypernatremia as she still struggles to meet her free water intake and continuously relies on her family for reminders. Though her case is certainly not typical, it highlights the added complexity of managing adipsic DI as it relies not only on DDAVP replacement, but replicating what is supposed to be an innate behavior. Presentation: 6/3/2024

Executive function and cortical thickness in biomarker aMCI

Introduction Memory deficits are the primary symptom in amnestic Mild Cognitive Impairment (aMCI); however, executive function (EF) deficits are common. The current study examined EF in aMCI based upon amyloid status (A+/A−) and regional atrophy in signature areas of Alzheimer’s disease (AD). Method Participants included 110 individuals with aMCI (A+ = 66; A− = 44) and 33 cognitively healthy participants (HP). EF was assessed using four neuropsychological assessment measures. The cortical thickness of the AD signature areas was calculated using structural MRI data. Results A + had greater EF deficits and cortical atrophy relative to A − in the supramarginal gyrus and superior parietal lobule. A − had greater EF deficits relative to HP, but no difference in signature area cortical thickness. Discussion The current study found that the degree of EF deficits in aMCI are a function of amyloid status and cortical thinning in the parietal cortex.

A coordinate-based meta-analysis of grey matter volume differences between adults with obsessive-compulsive disorder (OCD) and healthy controls

According to the cortico-striato-thalamo-cortical (CSTC) model of obsessive-compulsive disorder (OCD), the striatum plays a primary role in its neuropathophysiology. Hypothesising that volumetric alterations are more pronounced in subcortical areas of patients within the CSTC circuit compared to healthy controls (HCs), we conducted a coordinate-based meta-analysis of magnetic resonance imaging (MRI) studies. We included 26 whole-brain MRI studies, comprising 3,010 subjects: 1,508 patients (788 men, 720 women; mean age: 30.26 years, SD = 8.16) and 1,502 HCs (801 men, 701 women; mean age: 29.47 years, SD = 7.88). This meta-analysis demonstrated significant grey matter volume increases in the bilateral putamen, lateral globus pallidus, left parietal cortex, right pulvinar, and left cerebellum in adults with OCD, alongside decreases in the right hippocampus/caudate, bilateral medial frontal gyri, and other cortical regions. Volume increases were predominantly observed in subcortical areas, with the exception of the left parietal cortex and cerebellar dentate, while volume decreases were primarily cortical, aside from the right hippocampus/caudate. Further exploration of these neuropathophysiological correlates could inform specific prevention and treatment strategies, advancing precision mental health in clinical applications.

12227 The Battle Between Central And Nephrogenic Diabetes Insipidus

Abstract Disclosure: A.A. Luzuriaga Chavez: None. J.P. Hidalgo: None. A. Rao: None. N. Patel: None. Diabetes insipidus (DI) is a rare disorder characterized by excessive polyuria and polydipsia. The two main types include central diabetes insipidus (CDI), which results from antidiuretic hormone (ADH) deficiency and nephrogenic diabetes insipidus (NDI), defined by ADH resistance in the renal tubules. It can be challenging to distinguish between different types of DI in a critically ill patient. A 68-year-old female with a past medical history of hypertension, bipolar disorder came to the ER for complaints of chills and shortness of breath. She was transferred to the intensive care unit (ICU) for septic shock secondary to pneumonia and left pleural effusion. A chest tube was placed with improvement in her breathing and she was transferred out of the ICU. Four days later, the patient developed altered mental status, fevers and ICU was reconsulted due to concern for meningitis. A lumbar puncture was done with negative results but the brain MRI revealed ischemic sites involving both medial parietal cortices extending into both occipital poles, consistent with acute ischemia. Furthermore, the patient developed an increased urine output of 200ml per hour with a negative balance of 2.7L, increased sodium of 150, serum osmolality of 313 and urine osmolality of 196. The patient received desmopressin 1 mcg q 6 hrs with the persistence of hypernatremia. Upon further questioning, the patient had been on lithium therapy in the past for bipolar disorder. Amiloride 2.5mg BID was added to the treatment regimen. The patient’s hypernatremia and urine output improved and she was discharged on both amiloride and desmopressin to follow up for dose adjustments as needed. DI has a prevalence of 1 in 25000. Acquired CDI secondary to lesions in the hypophysis or hypothalamus highlights the major role of the central nervous system in regulating water homeostasis. This case report describes CDI developing after a stroke. Ischemia can cause hypoperfusion of osmoreceptors in the hypothalamus and posterior pituitary. Lithium can be frequently associated with NDI, usually seen in 20 to 40% of patients. Different mechanisms of action include lithium interference in renal collecting tubules by increasing cAMP in response to ADH and down-regulation of aquaporin-2 expression, which is accepted to be reversible with the cessation of the therapy. However, long-term treatment with lithium likely results in permanent NDI. Our patient had a history of lithium therapy which contributed to the development of symptoms of NDI and responded to a combination of desmopressin and amiloride. The successful therapy enforces the diagnosis of both a central and a peripheral pathology. Central and nephrogenic DI, despite stemming from distinct underlying causes, may concurrently manifest in critically ill patients. This case report emphasizes the need for physicians to evaluate for multiple causes of DI in a patient with water disturbances. Presentation: 6/1/2024

6468 Once-Weekly Semaglutide and Taste Perception in Women with Obesity

Abstract Disclosure: M. Jensterle Sever: None. J. Kovac: None. A. Vovk: None. S. Battelino: None. T. Battelino: None. A. Janez: None. Objective: Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue that causes weight loss by reducing appetite and lowering the desire for energy-dense, salty, and spicy foods, thereby reducing energy intake. We hypothesized that semaglutide would improve the taste sensitivity and modulate the tongue transcriptomic profile associated with gustatory coding in women with obesity.Design: We conducted a 16-week, single-blinded, randomized, placebo-controlled clinical trial involving 30 women aged 33.7 ± 6.1 years with a body mass index of 36.4 ± 4.4 kg/m2, randomized in a 1:1 ratio to once-weekly semaglutide 1.0 mg or a placebo (ClinicalTrials.gov number, NCT04263415). Methods: Taste sensitivity was assessed by strips impregnated with different concentrations of four basic tastes. Biopsies of the tongue were performed for the gene expression analysis. The brain responses were evaluated by functional MRI with the sweet solution dripping onto the tongue before and after a standardized meal intake. Results: Semaglutide improved the taste sensitivity expressed as a mean (± SD) from 11.9 ± 1.9 points to 14.4 ± 1.0 points, with an estimated treatment difference (ETD) of 2.5 points [95% CI, 1.7 to 3.3]. Genes EYA, PRMT8, CRLF1, and CYP1B1, associated with taste signaling transduction pathways, neural plasticity, and renewal of taste buds in the tongue, exhibited differential RNA expression across all tests performed by a multi-tiered analytical pipeline. Semaglutide increased functional activity in the angular gyrus of the parietal cortex in response to tasting the sweet solution compared to the distilled water 30 minutes after a standardized meal intake (semaglutide vs. placebo, p&amp;lt;0.001). Angular gyrus functions as a cross-modal hub where converging multisensory information is combined and integrated to comprehend and give sense to events and stimuli, manipulate mental representations, and solve familiar problems. It expresses GLP-1 receptor and is a part of the default mode network associated with shifting attention between rewarding and neutral stimuli, which has reduced connectivity in people with obesity. Conclusion: The present study provided evidence that semaglutide improved taste sensitivity, altered gene expression in the tongue linked to taste perception, and altered functional brain activity in an integrative hub beyond hypothalamic and midbrain reward circuitry in response to the sweet taste stimulus. Future studies will clarify whether the efficacy of semaglutide in treating obesity is also a »matter of taste«. Presentation: 6/1/2024