Unlocking the link: how hippocampal glutathione-glutamate coupling predicts cognitive impairment in multiple sclerosis patients.

Cognitive impairment is a common symptom of multiple sclerosis and profoundly impacts quality of life. Glutathione (GSH) and glutamate (Glu) are tightly linked in the brain, participating in cognitive function. However, GSH-Glu couplings in cognitive brain regions and their relationship with cognitive impairment in relapsing-remitting multiple sclerosis (RRMS) remains unclear. Forty-one RRMS patients and 43 healthy controls underwent magnetic resonance spectroscopy to measure GSH and Glu levels in the posterior cingulate cortex, medial prefrontal cortex and left hippocampus. Neuropsychological tests were used to evaluate the cognitive function. The Glu/GSH ratio was used to indicate the coupling between GSH and Glu and was tested as a predictor of cognitive performance. The results show that RRMS patients exhibited reduced hippocampal GSH and Glu levels, which were found to be significant predictors of worse verbal and visuospatial memory, respectively. Moreover, GSH levels were dissociated from Glu levels in the left hippocampus of RRMS patients. Hippocampal Glu/GSH ratio is significantly correlated with processing speed and has a greater predictive effect. Here we show the hippocampal Glu/GSH ratio could serve as a new potential marker for characterizing cognitive impairment in RRMS, providing a new direction for clinical detection of cognitive impairment.

Aberrant auditory metabolite levels and topological properties are associated with cognitive decline in presbycusis patients.

Presbycusis has been reported as related to cognitive decline, but its underlying neurophysiological mechanism is still unclear. This study aimed to investigate the relationship between metabolite levels, cognitive function, and node characteristics in presbycusis based on graph theory methods. Eighty-four elderly individuals with presbycusis and 63 age-matched normal hearing controls underwent magnetic resonance spectroscopy, functional magnetic resonance imaging scans, audiological assessment, and cognitive assessment. Compared with the normal hearing group, presbycusis patients exhibited reduced gamma-aminobutyric acid and glutamate levels in the auditory region, increased nodal characteristics in the temporal lobe and precuneus, as well as decreased nodal characteristics in the superior occipital gyrus and medial orbital. The right gamma-aminobutyric acid levels were negatively correlated with the degree centrality in the right precuneus and the executive function. Degree centrality in the right precuneus exhibited significant correlations with information processing speed and executive function, while degree centrality in the left medial orbital demonstrated a negative association with speech recognition ability. The degree centrality and node efficiency in the superior occipital gyrus exhibited a negative association with hearing loss and speech recognition ability, respectively. These observed changes indicate alterations in metabolite levels and reorganization patterns at the brain network level after auditory deprivation.

Identification of neurotransmitter imbalances in the cingulate cortex of NMOSD patients using magnetic resonance spectroscopy.

Cognitive impairment affects 29-67% of patients with neuromyelitis optica spectrum disorder. Previous studies have reported glutamate homeostasis disruptions in astrocytes, leading to imbalances in gamma-aminobutyric acid levels. However, the association between these neurotransmitter changes and cognitive deficits remains inadequately elucidated. Point RESolved Spectroscopy and Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy techniques were utilized to evaluate gamma-aminobutyric acid, glutamate, glutathione levels, and excitation/inhibition balance in the anterior cingulate cortex, posterior cingulate cortex, and occipital cortex of 39 neuromyelitis optica spectrum disorder patients and 41 healthy controls. Cognitive function was assessed using neurocognitive scales. Results showed decreased gamma-aminobutyric acid levels alongside increased glutamate, glutathione, and excitation/inhibition ratio in the anterior cingulate cortex and posterior cingulate cortex of neuromyelitis optica spectrum disorder patients. Specifically, within the posterior cingulate cortex of neuromyelitis optica spectrum disorder patients, decreased gamma-aminobutyric acid levels and increased excitation/inhibition ratio correlated significantly with anxiety scores, whereas glutathione levels predicted diminished executive function. The results suggest that neuromyelitis optica spectrum disorder patients exhibit dysregulation in the GABAergic and glutamatergic systems in their brains, where the excitation/inhibition imbalance potentially acts as a neuronal metabolic factor contributing to emotional disorders. Additionally, glutathione levels in the posterior cingulate cortex region may serve as predictors of cognitive decline, highlighting the potential benefits of reducing oxidative stress to safeguard cognitive function in neuromyelitis optica spectrum disorder patients.

Brain extended and closed forms glutathione levels decrease with age and extended glutathione is associated with visuospatial memory.

During aging, the brain is subject to greater oxidative stress (OS), which is thought to play a critical role in cognitive impairment. Glutathione (GSH), as a major antioxidant in the brain, can be used to combat OS. However, how brain GSH levels vary with age and their associations with cognitive function is unclear. In this study, we combined point-resolved spectroscopy and edited spectroscopy sequences to investigate extended and closed forms GSH levels in the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and occipital cortex (OC) of 276 healthy participants (extended form, 166 females, age range 20-70 years) and 15 healthy participants (closed form, 7 females, age range 26-56 years), and examined their relationships with age and cognitive function. The results revealed decreased extended form GSH levels with age in the PCC among 276 participants. Notably, the timecourse of extended form GSH level changes in the PCC and ACC differed between males and females. Additionally, positive correlations were observed between extended form GSH levels in the PCC and OC and visuospatial memory. Additionally, a decreased trend of closed form GSH levels with age was also observed in the PCC among 15 participants. Taken together, these findings enhance our understanding of the brain both closed and extended form GSH time course during normal aging and associations with sex and memory, which is an essential first step for understanding the neurochemical underpinnings of healthy aging.

Neurochemical and functional reorganization of the cognitive-ear link underlies cognitive impairment in presbycusis.

Recent studies suggest that the interaction between presbycusis and cognitive impairment may be partially explained by the cognitive-ear link. However, the underlying neurophysiological mechanisms remain largely unknown. In this study, we combined magnetic resonance spectroscopy (MRS) and resting-state functional magnetic resonance imaging (fMRI) to investigate auditory gamma-aminobutyric acid (GABA) and glutamate (Glu) levels, intra- and inter-network functional connectivity, and their relationships with auditory and cognitive function in 51 presbycusis patients and 51 well-matched healthy controls. Our results confirmed reorganization of the cognitive-ear link in presbycusis, including decreased auditory GABA and Glu levels and aberrant functional connectivity involving auditory networks (AN) and cognitive-related networks, which were associated with reduced speech perception or cognitive impairment. Moreover, mediation analyses revealed that decreased auditory GABA levels and dysconnectivity between the AN and default mode network (DMN) mediated the association between hearing loss and impaired information processing speed in presbycusis. These findings highlight the importance of AN-DMN dysconnectivity in cognitive-ear link reorganization leading to cognitive impairment, and hearing loss may drive reorganization via decreased auditory GABA levels. Modulation of GABA neurotransmission may lead to new treatment strategies for cognitive impairment in presbycusis patients.

Decreased auditory GABA+ concentrations in presbycusis demonstrated by edited magnetic resonance spectroscopy.

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central auditory system. Altered GABAergic neurotransmission has been found in both the inferior colliculus and the auditory cortex in animal models of presbycusis. Edited magnetic resonance spectroscopy (MRS), using the MEGA-PRESS sequence, is the most widely used technique for detecting GABA in the human brain. However, to date there has been a paucity of studies exploring changes to the GABA concentrations in the auditory region of patients with presbycusis. In this study, sixteen patients with presbycusis (5 males/11 females, mean age 63.1 ± 2.6 years) and twenty healthy controls (6 males/14 females, mean age 62.5 ± 2.3 years) underwent audiological and MRS examinations. Pure tone audiometry from 0.125 to 8 kHz and tympanometry were used to assess the hearing abilities of all subjects. The pure tone average (PTA; the average of hearing thresholds at 0.5, 1, 2 and 4 kHz) was calculated. The MEGA-PRESS sequence was used to measure GABA+ concentrations in 4 × 3 × 3 cm(3) volumes centered on the left and right Heschl's gyri. GABA+ concentrations were significantly lower in the presbycusis group compared to the control group (left auditory regions: p = 0.002, right auditory regions: p = 0.008). Significant negative correlations were observed between PTA and GABA+ concentrations in the presbycusis group (r = -0.57, p = 0.02), while a similar trend was found in the control group (r = -0.40, p = 0.08). These results are consistent with a hypothesis of dysfunctional GABAergic neurotransmission in the central auditory system in presbycusis and suggest a potential treatment target for presbycusis.

Association between hearing ability and cortical morphology in the elderly: multiparametric mapping, cognitive relevance, and neurobiological underpinnings.

BACKGROUND: Hearing impairment is a common condition in the elderly. However, a comprehensive understanding of its neural correlates is still lacking. METHODS: We recruited 284 elderly adults who underwent structural MRI, magnetic resonance spectroscopy, audiometry, and cognitive assessments. Individual hearing abilities indexed by pure tone average (PTA) were correlated with multiple structural MRI-derived cortical morphological indices. For regions showing significant correlations, mediation analyses were performed to examine their role in the relationship between hearing ability and cognitive function. Finally, the correlation maps between hearing ability and cortical morphology were linked with publicly available connectomic gradient, transcriptomic, and neurotransmitter maps. FINDINGS: Poorer hearing was related to cortical thickness (CT) reductions in widespread regions and gyrification index (GI) reductions in the right Area 52 and Insular Granular Complex. The GI in the right Area 52 mediated the relationship between hearing ability and executive function. This mediating effect was further modulated by glutamate and N-acetylaspartate levels in the right auditory region. The PTA-CT correlation map followed microstructural connectomic hierarchy, were related to genes involved in certain biological processes (e.g., glutamate metabolic process), cell types (e.g., excitatory neurons and astrocytes), and developmental stages (i.e., childhood to young adulthood), and covaried with dopamine receptor 1, dopamine transporter, and fluorodopa. The PTA-GI correlation map was related to 5-hydroxytryptamine receptor 2a. INTERPRETATION: Poorer hearing is associated with cortical thinning and folding reductions, which may be engaged in the relationship between hearing impairment and cognitive decline in the elderly and have different neurobiological substrates. FUNDING: See the Acknowledgements section.

Reduced brain glutathione levels during normal aging are associated with visuospatial memory.

During aging, the brain is subject to greater oxidative stress (OS), which is thought to play a critical role in cognitive impairment. Glutathione (GSH), as a major antioxidant in the brain, can be used to combatting OS. However, how brain GSH levels vary with age and their associations with cognitive function remain unclear. In this study, we combined point-resolved spectroscopy and edited spectroscopy sequences to investigate GSH levels in the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and occipital cortex (OC) of 276 healthy participants (166 females, age range 20-70 years) and examined their relationships with age and cognitive function. The results revealed decreased GSH levels with age in the PCC among all participants. Notably, the timecourse of GSH level changes in the PCC and ACC differed between males and females. Additionally, positive correlations were observed between GSH levels in the PCC and OC and visuospatial memory. Taken together, these findings enhance our understanding of the brain GSH timecourse during normal aging and associations with sex and memory, which is an essential first step for understanding the neurochemical underpinnings of OS-related diseases.

Classification of Alzheimer's Disease Based on Deep Learning of Brain Structural and Metabolic Data.

To improve the diagnosis and classification of Alzheimer's disease (AD), a modeling method is proposed based on the combining magnetic resonance images (MRI) brain structural data with metabolite levels of the frontal and parietal regions. First, multi-atlas brain segmentation technology based on T1-weighted images and edited magnetic resonance spectroscopy (MRS) were used to extract data of 279 brain regions and levels of 12 metabolites from regions of interest (ROIs) in the frontal and parietal regions. The t-test combined with false discovery rate (FDR) correction was used to reduce the dimensionality in the data, and MRI structural data of 54 brain regions and levels of 4 metabolites that obviously correlated with AD were screened out. Lastly, the stacked auto-encoder neural network (SAE) was used to classify AD and healthy controls (HCs), which judged the effect of classification method by fivefold cross validation. The results indicated that the mean accuracy of the five experimental model increased from 96 to 100%, the AUC value increased from 0.97 to 1, specificity increased from 90 to 100%, and F1 value increased from 0.97 to 1. Comparing the effect of each metabolite on model performance revealed that the gamma-aminobutyric acid (GABA) + levels in the parietal region resulted in the most significant improvement in model performance, with the accuracy rate increasing from 96 to 98%, the AUC value increased from 0.97 to 0.99 and the specificity increasing from 90 to 95%. Moreover, the GABA + levels in the parietal region was significantly correlated with Mini Mental State Examination (MMSE) scores of patients with AD (r = 0.627), and the F statistics were largest (F = 25.538), which supports the hypothesis that dysfunctional GABAergic system play an important role in the pathogenesis of AD. Overall, our findings support that a comprehensive method that combines MRI structural and metabolic data of brain regions can improve model classification efficiency of AD.

High-Frequency Hearing Loss Is Associated With Anxiety and Brain Structural Plasticity in Older Adults.

Age-related hearing loss (ARHL) is a kind of symmetrical and slow sensorineural hearing loss, which is a common condition in older adults. The characteristic of ARHL is hearing loss beginning in the high-frequency region and spreading toward low-frequency with age. Previous studies have linked it to anxiety, suggesting that brain structure may be involved in compensatory plasticity after partial hearing deprivation. However, the neural mechanisms of underlying ARHL-related anxiety remain unclear. The purpose of this cross-sectional study was to explore the interactions among high-frequency hearing loss and anxiety as well as brain structure in older adults. Sixty-seven ARHL patients and 68 normal hearing (NH) controls participated in this study, and the inclusion criterion of ARHL group was four-frequency (0.5, 1, 2, and 4 kHz) pure tone average (PTA) > 25 decibels hearing level of the better hearing ear. All participants performed three-dimensional T1-weighted magnetic resonance imaging (MRI), pure tone audiometry tests, anxiety and depression scales. Our results found gray matter volume (GMV) decreased in 20 brain regions in the ARHL group compared with the NH group, and a positive correlation existed between high-frequency pure tone audiometry (H-PT) and anxiety scores in the ARHL group. Among 20 brain regions, we also found the GMVs of the middle cingulate cortex (MCC), and the hippocampal/parahippocampal (H-P) regions were associated with H-PT and anxiety scores in all participants separately. However, the depressive symptoms indicated no relationship with hearing assessment or GMVs. Our findings revealed that the crucial role of MCC and H-P in a link of anxiety and hearing loss in older adults.

Brain Frequency-Specific Changes in the Spontaneous Neural Activity Are Associated With Cognitive Impairment in Patients With Presbycusis.

Presbycusis (PC) is characterized by preferential hearing loss at high frequencies and difficulty in speech recognition in noisy environments. Previous studies have linked PC to cognitive impairment, accelerated cognitive decline and incident Alzheimer's disease. However, the neural mechanisms of cognitive impairment in patients with PC remain unclear. Although resting-state functional magnetic resonance imaging (rs-fMRI) studies have explored low-frequency oscillation (LFO) connectivity or amplitude of PC-related neural activity, it remains unclear whether the abnormalities occur within all frequency bands or within specific frequency bands. Fifty-one PC patients and fifty-one well-matched normal hearing controls participated in this study. The LFO amplitudes were investigated using the amplitude of low-frequency fluctuation (ALFF) at different frequency bands (slow-4 and slow-5). PC patients showed abnormal LFO amplitudes in the Heschl's gyrus, dorsolateral prefrontal cortex (dlPFC), frontal eye field and key nodes of the speech network exclusively in slow-4, which suggested that abnormal spontaneous neural activity in PC was frequency dependent. Our findings also revealed that stronger functional connectivity between the dlPFC and the posterodorsal stream of auditory processing, as well as lower functional coupling between the PCC and key nodes of the DMN, which were associated with cognitive impairments in PC patients. Our study might underlie the cross-modal plasticity and higher-order cognitive participation of the auditory cortex after partial hearing deprivation. Our findings indicate that frequency-specific analysis of ALFF could provide valuable insights into functional alterations in the auditory cortex and non-auditory regions involved in cognitive impairment associated with PC.

CT assessment of preoperative nutritional status in gastric cancer: severe low skeletal muscle mass and obesity-related low skeletal muscle mass are unfavorable factors of postoperative complications.

BACKGROUND: Computed tomography (CT) has become an important technique for assessing skeletal muscle mass. Low skeletal muscle mass (LSMM) is considered an unfavorable factor for postoperative complications in patients with gastric cancer (GC). METHODS: Patients who underwent laparoscopic gastrectomy for GC were included. Skeletal muscle mass at the third lumbar vertebra (L3) level was measured by preoperatively using CT. The patients were divided into an LSMM group and a non-LSMM group and the intergroup differences were analyzed. Furthermore, we divided the LSMM group into mild and severe LSMM subgroups. The study also analyzed the influence of obesity-related LSMM on postoperative complications. RESULTS: A total of 409 patients were enrolled; of them, 265 had LSMM and 41 had severe LSMM. LSMM was associated with age, body mass index, and Nutritional Risk Screening 2002 score. In the multivariate analysis, LSMM was not related to postoperative complications. Further analysis revealed that severe LSMM was a risk factor for postoperative complications. The study also found that the risk of postoperative complications was significantly increased in patients with obesity-related LSMM. CONCLUSIONS: LSMM was not significantly correlated with postoperative complications. Severe LSMM and obesity-related LSMM are unfavorable factors for postoperative complications with GC after gastrectomy.

Programmed Size-Changeable Nanotheranostic Agents for Enhanced Imaging-Guided Chemo/Photodynamic Combination Therapy and Fast Elimination.

An ideal nanotheranostic agent should be able to achieve efficient tumor accumulation, retention, and fast elimination after its theranostic functions exhausts. However, there is an irreconcilable contradiction on optimum sizes for effective tumor retention and fast elimination. Herein, a programmed size-changeable nanotheranostic agent based on polyprodrug-modified iron oxide nanoparticles (IONPs) and aggregation-induced emission photosensitizer is developed for enhanced magnetic resonance imaging (MRI)-guided chemo/photodynamic combination therapy. The nano-sized theranostic agents with an initial diameter of about 90 nm can accumulate in tumor tissue through passive targeting. In the acidic tumor microenvironment, large aggregates of IONPs are formed, realizing enhanced tumor retention and MR signal enhancement. Under the guidance of MRI, light irradiation is applied to the tumor site for triggering the generation of reactive oxygen species and drug release. Moreover, after chemo/photodynamic combination therapy, the large-sized aggregates are re-dispersed into small-sized IONPs for fast elimination, reducing the risk of toxicity caused by long-term retention. Therefore, this study provides a promising size-changeable strategy for the development of nanotheranostic agents.

Succinate dehydrogenase deficient gastrointestinal stromal tumor in a three month old boy with a fatal clinical course: a case report and review of literature.

BACKGROUND: Succinate dehydrogenase deficient gastrointestinal stromal tumors (SDH-deficient GISTs), which lack KIT or PDGFRA mutations demonstrate unique clinical and pathological features, and they respond poorly to standard targeted therapy. We herein present a novel case of SDH-deficient GIST in a three-month-old infant's colon mesentery, and he is the youngest patientto date. CASE PRESENTATION: The infantpresented with complaints of blood in the stool. CT showed a 6.3 × 4.6 cm mass in the left lower retroperitoneal. Complete resection of tumor and segmental bowel resection was performed without regional lymphadenectomy. Histologically, tumor cells were distinctive in their multinodular colon wall involvement with interspersed tracts of colon wall smooth muscle. The tumor was composed mainly of epithelioid cells. Immunohistochemically, the tumor cells were positive for Vim, CD117, PDGFR, while negative for SDHB. Mutational analysis showed a synonymous mutation for SDHB and wild-type for KIT and PDGFRA. Two months after surgery, metastases were found and Imatinib was administered. Unfortunately, the disease continued to progress, and the infant died 5 months after surgery. CONCLUSIONS: SDH-deficient GISTs comprise a subgroup of a relatively rare tumor type and show a number of clinically and biologically unique features, especially for infants. It is of great importance to developing new therapeutic targets and novel specific drugs.

High-Frequency Cochlear Amplifier Dysfunction: A Dominating Contribution to the Cognitive-Ear Link.

Objective: The objective of this study was to investigate the role of the high-frequency cochlear dysfunction in the cognitive-ear link. Methods: Seventy-four presbycusis patients (PC group) and seventy-one age-, sex-, and education-level matched normal hearing controls (NH group) were recruited in this study. Participants underwent a battery of cognitive tests estimated by Montreal Cognitive Assessment (MoCA), Stroop Color-Word Interference Test (Stroop), Symbol Digit Modalities Test (SDMT), Auditory Verbal Learning Test (AVLT), and Trail-Making Test (TMT-A and B), as well as auditory tests including distortion product otoacoustic emission (DPOAE), pure tone (PT) thresholds, and speech reception thresholds (SRT). Data were analyzed using the factor analysis, partial correlation analysis, multiple linear regression models, and mediation models. Results: Distortion product otoacoustic emission detection amplitudes and PT thresholds performed worse gradually from low to high frequencies in both the NH and PC groups. High-frequency DPOAE (H-DPOAE) was significantly correlated with cognitive domains in the PC group (AVLT: r = 0.30, p = 0.04; SDMT: r = 0.36, p = 0.01; Stroop: r = -0.32, p = 0.03; TMT-A: r = -0.40, p = 0.005; TMT-B: r = -0.34, p = 0.02). Multiple linear regression models showed that H-DPOAE predicted cognitive impairment effectively for aspects of memory (R 2 = 0.27, 95% CI, 0.03 to 1.55), attention (R 2 = 0.32, 95% CI, -6.18 to -0.40), processing speed (R 2 = 0.37, 95% CI, 0.20 to 1.64), and executive function (TMT-A: R 2 = 0.34, 95% CI, -5.52 to 1.03; TMT-B: R 2 = 0.29, 95% CI, -11.30 to -1.12). H-DPOAE directly affected cognition and fully mediated the relationship between pure tone average (PTA)/SRT and cognitive test scores, excluding MoCA. Conclusion: This study has demonstrated that the high-frequency cochlear amplifier dysfunction has a direct predictive effect on the cognitive decline and makes a large contribution to the cognitive-ear link.

Clinicopathological characteristics and surgical outcomes of sarcomatoid hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common type of cancer and the fourth leading cause of cancer-related death worldwide. Sarcomatoid HCC, which contains poorly differentiated carcinomatous and sarcomatous components, is a rare histological subtype of HCC that differs from conventional HCC. It is highly aggressive and has a poor prognosis. Its clinicopathological characteristics, surgical outcomes and underlying mechanisms of its highly aggressive nature have not been fully elucidated. AIM: To examine the clinicopathological characteristics and surgical outcomes of sarcomatoid HCC and explore the histogenesis of sarcomatoid HCC. METHODS: In total, 196 patients [41 sarcomatoid HCC and 155 high-grade (Edmondson-Steiner grade III or IV) HCC] who underwent surgical resection between 2007 and 2017 were retrospectively reviewed. The characteristics and surgical outcomes of sarcomatoid HCC were compared with those of patients with high-grade HCC. The histological composition of invasive and metastatic sarcomatoid HCCs was evaluated. RESULTS: Sarcomatoid HCC was more frequently diagnosed at an advanced stage with a larger tumor and higher rates of nonspecific symptom, adjacent organ invasion and lymph node metastasis than high-grade HCC (all P < 0.05). Compared with high-grade HCC patients, sarcomatoid HCC patients are less likely to have typical dynamic imaging features of HCC (44.4% vs 72.7%, P = 0.001) and elevated serum alpha-fetoprotein levels (> 20 ng/mL; 36.6% vs 78.7%, P < 0.001). The sarcomatoid group had a significantly shorter median recurrence-free survival (5.6 mo vs 16.4 mo, log-rank P < 0.0001) and overall survival (10.5 mo vs 48.1 mo, log-rank P < 0.0001) than the high-grade group. After controlling for confounding factors, the sarcomatoid subtype was identified as an independent predictor of poor prognosis. Pathological analyses indicated that invasive and metastatic lesions were mainly composed of carcinomatous components. CONCLUSION: Sarcomatoid HCC was associated with a more advanced stage, atypical dynamic imaging, lower serum alpha-fetoprotein levels and a worse prognosis. The highly aggressive nature of sarcomatoid HCC is perhaps mediated by carcinomatous components.

Hearing Loss and Cognition Among Older Adults in a Han Chinese Cohort.

Presbycusis (PC) is associated with cognitive decline and incident dementia. Speech reception thresholds (SRT) are used to assess speech detection, which points toward a central component of PC. However, to the best of our knowledge, no previous study has reported the relationship between SRT and cognitive function in older adults in a Han Chinese cohort. Therefore, in this study, we investigate the association of hearing loss, indexed using pure tone average (PTA) and SRT, with cognitive function in a Han Chinese cohort using a standardized neurocognitive battery. Subjects (aged ≥60 years) with no history of psychiatric or neurological diseases were recruited. All subjects underwent a battery of neuropsychological and auditory tests. According to the PTA of the better ear, the subjects were further divided into PC and normal PTA (NP) groups. Regression analyses were performed to examine the relationship between cognitive function and hearing loss in the PC and NP groups and all subjects when controlling for age, sex, education level, diabetes, smoking, and hypertension. Cognitive function was significantly associated with PTA and SRT in all subjects. In all subjects, the correlations between non-verbal cognitive scores and SRT were stronger than those between non-verbal cognitive scores and PTA, whereas the correlations between verbal cognitive scores and PTA were stronger than those between verbal cognitive scores and SRT. Moreover, the correlations between PTA or SRT and cognitive function in the PC group were in principle stronger than those in the NP group. Our findings indicate that cognitive function is significantly associated with PTA and SRT in older adults in a Han Chinese cohort. Therefore, SRT could be an important auditory test for exploring cognitive decline in PC and could complement PTA.

Gray Matter Atrophy Is Associated With Cognitive Impairment in Patients With Presbycusis: A Comprehensive Morphometric Study.

Presbycusis (PC) is characterized by bilateral sensorineural hearing loss at high frequencies and speech-perception difficulties in noisy environments and has a strikingly detrimental impact on cognitive function. As the neural consequences of PC may involve the whole brain, we hypothesized that patients with PC would show structural alterations not only in the auditory cortex but also in the cortexes involved in cognitive function. The purpose of this study was to use surface-based morphometry (SBM) analysis to elucidate whole-brain structural differences between patients with PC and age-matched normal hearing controls. Three-dimensional T1-weighted MR images of 26 patients with mild PC and 26 age-, sex- and education-matched healthy controls (HCs) were acquired. All participants underwent a battery of neuropsychological tests. Our results revealed gray matter atrophy in several auditory cortical areas, nodes of the default mode network (DMN), including the bilateral precuneus and inferior parietal lobule, the right posterior cingulate cortex (PCC), and the right insula of patients with PC compared to that in the HCs. Our findings also revealed that hearing loss was associated with reduced gray matter volume in the right primary auditory cortex of patients with PC. Moreover, structural alterations in the nodes of the DMN were associated with cognitive impairments in PC patients. Additionally, this study provides evidence that a thicker right insula is associated with better speech perception in patients with PC. Based on these findings, we argue that the onset of PC seems to trigger its own cascade of conditions, including a need for increased cognitive resources during speech comprehension, which might lead to auditory and cognition-related cortical reorganization.

Buyang Huanwu Decoction promotes growth and differentiation of neural progenitor cells: using a serum pharmacological method.

Buyang Huanwu Decoction (BYHWD), a traditional Chinese medicine, has been developed as a drug to be used for treatment of stroke for hundreds of years. However, the underlying mechanisms remain unknown. In this study, a serum pharmacological method was employed to investigate the effects of BYHWD on growth and differentiation of cultured neural progenitor cells derived from embryonic hippocampus. In culture medium containing BYHWD, the average neurite length of neural progenitor cells grew significantly longer than in control serum without BYHWD. Moreover, more neurofilament (NF) positive cells and glial fibrillary acidic protein (GFAP) positive cells were detected in the presence of BYHWD. The concentration of intracellular Ca(2+) in progenitor cells cultured with BYHWD was significantly lower than that cultured without BYHWD. These results suggest that BYHWD may promote growth and differentiation of neural progenitor cells.

Alterations of GABA and glutamate-glutamine levels in premenstrual dysphoric disorder: a 3T proton magnetic resonance spectroscopy study.

Increasing evidence has suggested that the GABAergic neurotransmitter system is involved in the pathogenesis of premenstrual dysphoric disorder (PMDD). We used proton magnetic resonance spectroscopy ((1)H MRS) to investigate whether PMDD is associated with alterations in brain GABA levels. Levels of glutamate-glutamine (Glx) were also explored. Participants comprised 22 women with PMDD and 22 age-matched healthy controls who underwent 3T (1)H MRS during the late luteal phase of the menstrual cycle. GABA+ and Glx levels were quantified in the anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) and the left basal ganglia (ltBG). Water-scaled GABA+ concentrations and GABA+/tCr ratios were significantly lower in both the ACC/mPFC and ltBG regions of PMDD women than in healthy controls. Glx/tCr ratios were significantly higher in the ACC/mPFC region of PMDD women than healthy controls. Our preliminary findings provide the first report of abnormal levels of GABA+ and Glx in mood-related brain regions of women with PMDD, indicating that dysregulation of the amino acid neurotransmitter system may be an important neurobiological mechanism in the pathogenesis of PMDD.