Neural basis of false recognition in Alzheimer's disease and dementia with lewy bodies.

In Alzheimer's disease (AD), reports on the association between false recognition and brain structure have been inconsistent. In dementia with Lewy bodies (DLB), no such association has been reported. This study aimed to identify brain regions associated with false recognition in AD and DLB by analyzing regional gray matter volume (rGMV). We included 184 patients with AD and 60 patients with DLB. The number of false recognitions was assessed using the Alzheimer's Disease Assessment Scale' word recognition task. Brain regions associated with the number of false recognitions were examined by voxel-based morphometry analysis. The number of false recognitions significantly negatively correlated with rGMV in the bilateral hippocampus, left parahippocampal gyrus, bilateral amygdala, and bilateral entorhinal cortex in patients with AD (p < 0.05, family-wise error [FEW] corrected) and in the bilateral hippocampus, left parahippocampal gyrus, right inferior frontal gyrus, right middle frontal gyrus, right basal forebrain, right insula, left medial and lateral orbital gyri, and left fusiform in those with DLB (p < 0.05, FWE corrected). Bilateral hippocampus and left parahippocampal gyrus were associated with false recognition in both diseases. However, we found there were regions where the association between false recognition and rGMV differed from disease to disease.

Sex difference in neural responses to gaming cues in Internet gaming disorder: Implications for why males are more vulnerable to cue-induced cravings than females.

BACKGROUND: Although drug addiction studies have shown that females are more likely to become addicted and sensitive to drug cues, this feature seems reversed in Internet gaming disorder (IGD), of which males are more likely to be sufferers. Given the prevalence of IGD in the male population, the current study was set to examine the potential effect of sex on IGD's craving using a cue reactivity task. METHODS: Sixty-five (32 males) IGD subjects underwent fMRI scanning during exposure to visual gaming cues and neutral cues. Brain responses to gaming cues relative to neutral cues were examined within two groups separately. In addition, Granger causal analysis (GCA) was conducted to investigate how the effective connectivity patterns were altered in male and female IGD subjects. RESULTS: When facing gaming cues, lower regions of brain activation were observed in males compared to females, including the left anterior cingulate cortex (ACC), the superior frontal gyrus and the posterior cingulate cortex (PCC); GCA results, using the PCC as the ROI, showed higher middle temporal gyrus-PCC-right ACC/parahippocampal gyrus effective connectivity in males as compared with females, when exposed to gaming cues. CONCLUSION: The results indicate that gaming cues could more severely disturb male IGD subjects' inhibition control function over game-elicited cravings compared to females, which might make it hard for males to control their game cravings and stop their gaming behaviors. This conclusion is valuable in understanding why males are more vulnerable to IGD than females.

Functional Connectivity Between the Posterior Default Mode Network and Parahippocampal Gyrus Is Disrupted in Older Adults with Subjective Cognitive Decline and Correlates with Subjective Memory Ability.

BACKGROUND: Subjective cognitive decline (SCD) is associated with increased risk of developing Alzheimer's disease (AD). However, the underlying mechanisms for this association remain unclear. Neuroimaging studies suggest the earliest AD-related changes are large-scale network disruptions, beginning in the posterior default mode (pDMN) network. OBJECTIVE: To examine the association between SCD and pDMN network connectivity with medial temporal lobe (MTL) regions using resting-state functional magnetic resonance imaging. METHODS: Forty-nine participants with either SCD (n = 23, 12 females; mean age: 70.7 (5.5)) or who were cognitively unimpaired (CU; n = 26, 16 females, mean age: 71.42 (7.3)) completed the Memory Functioning Questionnaire, a measure of subjective memory, and underwent resting state functional MRI at 3 Tesla. Functional connectivity between the posterior cingulate cortex (PCC), as the key pDMN node, and MTL regions were compared between SCD and CU groups. Further, the association between pDMN-MTL connectivity and the Frequency of Forgetting subscale of the Memory Functioning Questionnaire was examined. RESULTS: Connectivity between the PCC-MTL was observed in the CU group but was absent in SCD (t(47) = 2.69, p = 0.01). Across all participants, self-perception of frequency of forgetting, but not objective memory, was strongly correlated with connectivity between the PCC-left parahippocampal gyrus (r = 0.43, p = 0.002). CONCLUSION: These findings support the hypothesis that increased AD risk in SCD may be mediated by disrupted pDMN-parahippocampal connectivity. In addition, these findings suggest that frequency of forgetting may serve as a potential biomarker of SCD due to incipient AD.

Longitudinal changes in regional cerebral blood flow in late middle-aged and older adults with treated and untreated obstructive sleep apnea.

Obstructive sleep apnea (OSA) is associated with abnormal cerebral perfusion at wakefulness, but whether these anomalies evolve over time is unknown. Here, we examined longitudinal changes in regional cerebral blood flow (rCBF) distribution in late middle-aged and older adults with treated or untreated OSA. Twelve controls (64.8 ± 8.0 years) and 23 participants with newly diagnosed OSA (67.8 ± 6.2 years) were evaluated with polysomnography and cerebral 99m Tc-HMPAO single-photon emission computed tomography during wakeful rest. OSA participants were referred to a sleep apnea clinic and 13 of them decided to start continuous positive airway pressure (CPAP). Participants were tested again after 18 months. Voxel-based analysis and extracted relative rCBF values were used to assess longitudinal changes. Untreated OSA participants showed decreased relative rCBF in the left hippocampus and the right parahippocampal gyrus over time, while treated participants showed trends for increased relative rCBF in the left hippocampus and the right parahippocampal gyrus. No changes were found over time in controls. Untreated OSA is associated with worsening relative rCBF in specific brain areas over time, while treated OSA shows the opposite. Considering that OSA possibly accelerates cognitive decline in older adults, CPAP treatment could help reduce risk for cognitive impairment.

Altered thalamic connectivity in insomnia disorder during wakefulness and sleep.

Insomnia disorder is the most common sleep disorder and has drawn increasing attention. Many studies have shown that hyperarousal plays a key role in the pathophysiology of insomnia disorder. However, the specific brain mechanisms underlying insomnia disorder remain unclear. To elucidate the neuropathophysiology of insomnia disorder, we investigated the brain functional networks of patients with insomnia disorder and healthy controls across the sleep-wake cycle. EEG-fMRI data from 33 patients with insomnia disorder and 31 well-matched healthy controls during wakefulness and nonrapid eye movement sleep, including N1, N2 and N3 stages, were analyzed. A medial and anterior thalamic region was selected as the seed considering its role in sleep-wake regulation. The functional connectivity between the thalamic seed and voxels across the brain was calculated. ANOVA with factors "group" and "stage" was performed on thalamus-based functional connectivity. Correlations between the misperception index and altered functional connectivity were explored. A group-by-stage interaction was observed at widespread cortical regions. Regarding the main effect of group, patients with insomnia disorder demonstrated decreased thalamic connectivity with the left amygdala, parahippocampal gyrus, putamen, pallidum and hippocampus across wakefulness and all three nonrapid eye movement sleep stages. The thalamic connectivity in the subcortical cluster and the right temporal cluster in N1 was significantly correlated with the misperception index. This study demonstrated the brain functional basis in insomnia disorder and illustrated its relationship with sleep misperception, shedding new light on the brain mechanisms of insomnia disorder and indicating potential therapeutic targets for its treatment.

Disrupted parahippocampal and midbrain function underlie slower verbal learning in adolescent-onset regular cannabis use.

RATIONALE: Prolonged use of cannabis, the most widely used illicit drug worldwide, has been consistently associated with impairment in memory and verbal learning. Although the neurophysiological underpinnings of these impairments have been investigated previously using functional magnetic resonance imaging (fMRI), while performing memory tasks, the results of these studies have been inconsistent and no clear picture has emerged yet. Furthermore, no previous studies have investigated trial-by-trial learning. OBJECTIVES: We aimed to investigate the neural underpinnings of impaired verbal learning in cannabis users as estimated over repeated learning trials. METHODS: We studied 21 adolescent-onset regular cannabis users and 21 non-users using fMRI performed at least 12 h after last cannabis use, while they performed a paired associate verbal learning task that allowed us to examine trial-by-trial learning. Brain activation during repeated verbal encoding and recall conditions of the task was indexed using the blood oxygen level-dependent haemodynamic response fMRI signal. RESULTS: There was a significant improvement in recall score over repeated trials indicating learning occurring across the two groups of participants. However, learning was significantly slower in cannabis users compared to non-users (p = 0.032, partial eta-squared = 0.108). While learning verbal stimuli over repeated encoding blocks, non-users displayed progressive increase in recruitment of the midbrain, parahippocampal gyrus and thalamus (p = 0.00939, partial eta-squared = 0.180). In contrast, cannabis users displayed a greater but disrupted activation pattern in these regions, which showed a stronger correlation with new word-pairs learnt over the same blocks in cannabis users than in non-users. CONCLUSIONS: These results suggest that disrupted medial temporal and midbrain function underlie slower learning in adolescent-onset cannabis users.

Identification of neural networks preferentially engaged by epileptogenic mass lesions through lesion network mapping analysis.

Lesion network mapping (LNM) has been applied to true lesions (e.g., cerebrovascular lesions in stroke) to identify functionally connected brain networks. No previous studies have utilized LNM for analysis of intra-axial mass lesions. Here, we implemented LNM for identification of potentially vulnerable epileptogenic networks in mass lesions causing medically-refractory epilepsy (MRE). Intra-axial brain lesions were manually segmented in patients with MRE seen at our institution (EL_INST). These lesions were then normalized to standard space and used as seeds in a high-resolution normative resting state functional magnetic resonance imaging template. The resulting connectivity maps were first thresholded (pBonferroni_cor < 0.05) and binarized; the thresholded binarized connectivity maps were subsequently summed to produce overall group connectivity maps, which were compared with established resting-state networks to identify potential networks prone to epileptogenicity. To validate our data, this approach was also applied to an external dataset of epileptogenic lesions identified from the literature (EL_LIT). As an additional exploratory analysis, we also segmented and computed the connectivity of institutional non-epileptogenic lesions (NEL_INST), calculating voxel-wise odds ratios (VORs) to identify voxels more likely to be functionally-connected with EL_INST versus NEL_INST. To ensure connectivity results were not driven by anatomical overlap, the extent of lesion overlap between EL_INST, and EL_LIT and NEL_INST was assessed using the Dice Similarity Coefficient (DSC, lower index ~ less overlap). Twenty-eight patients from our institution were included (EL_INST: 17 patients, 17 lesions, 10 low-grade glioma, 3 cavernoma, 4 focal cortical dysplasia; NEL_INST: 11 patients, 33 lesions, all brain metastases). An additional 23 cases (25 lesions) with similar characteristics to the EL_INST data were identified from the literature (EL_LIT). Despite minimal anatomical overlap of lesions, both EL_INST and EL_LIT showed greatest functional connectivity overlap with structures in the Default Mode Network, Frontoparietal Network, Ventral Attention Network, and the Limbic Network-with percentage volume overlap of 19.5%, 19.1%, 19.1%, and 12.5%, respectively-suggesting them as networks consistently engaged by epileptogenic mass lesions. Our exploratory analysis moreover showed that the mesial frontal lobes, parahippocampal gyrus, and lateral temporal neocortex were at least twice as likely to be functionally connected with the EL_INST compared to the NEL_INST group (i.e. Peak VOR > 2.0); canonical resting-state networks preferentially engaged by EL_INSTs were the Limbic and the Frontoparietal Networks (Mean VOR > 1.5). In this proof of concept study, we demonstrate the feasibility of LNM for intra-axial mass lesions by showing that ELs have discrete functional connections and may preferentially engage in discrete resting-state networks. Thus, the underlying normative neural circuitry may, in part, explain the propensity of particular lesions toward the development of MRE. If prospectively validated, this has ramifications for patient counseling along with both approach and timing of surgery for lesions in locations prone to development of MRE.

Decreased effective connection from the parahippocampal gyrus to the prefrontal cortex in Internet gaming disorder: A MVPA and spDCM study.

OBJECTIVES: Understanding the neural mechanisms underlying Internet gaming disorder (IGD) is essential for the condition's diagnosis and treatment. Nevertheless, the pathological mechanisms of IGD remain elusive at present. Hence, we employed multi-voxel pattern analysis (MVPA) and spectral dynamic causal modeling (spDCM) to explore this issue. METHODS: Resting-state fMRI data were collected from 103 IGD subjects (male = 57) and 99 well-matched recreational game users (RGUs, male = 51). Regional homogeneity was calculated as the feature for MVPA based on the support vector machine (SVM) with leave-one- out cross-validation. Mean time series data extracted from the brain regions in accordance with the MVPA results were used for further spDCM analysis. RESULTS: Results display a high accuracy of 82.67% (sensitivity of 83.50% and specificity of 81.82%) in the classification of the two groups. The most discriminative brain regions that contributed to the classification were the bilateral parahippocampal gyrus (PG), right anterior cingulate cortex (ACC), and middle frontal gyrus (MFG). Significant correlations were found between addiction severity (IAT and DSM scores) and the ReHo values of the brain regions that contributed to the classification. Moreover, the results of spDCM showed that compared with RGU, IGD showed decreased effective connectivity from the left PG to the right MFG and from the right PG to the ACC and decreased self-connection in the right PG. CONCLUSIONS: These results show that the weakening of the PG and its connection with the prefrontal cortex, including the ACC and MFG, may be an underlying mechanism of IGD.

Impaired Parahippocampal Gyrus-Orbitofrontal Cortex Circuit Associated with Visuospatial Memory Deficit as a Potential Biomarker and Interventional Approach for Alzheimer Disease.

The parahippocampal gyrus-orbitofrontal cortex (PHG-OFC) circuit in humans is homologous to the postrhinal cortex (POR)-ventral lateral orbitofrontal cortex (vlOFC) circuit in rodents. Both are associated with visuospatial malfunctions in Alzheimer's disease (AD). However, the underlying mechanisms remain to be elucidated. In this study, we explored the relationship between an impaired POR-vlOFC circuit and visuospatial memory deficits through retrograde tracing and in vivo local field potential recordings in 5XFAD mice, and investigated alterations of the PHG-OFC circuit by multi-domain magnetic resonance imaging (MRI) in patients on the AD spectrum. We demonstrated that an impaired glutamatergic POR-vlOFC circuit resulted in deficient visuospatial memory in 5XFAD mice. Moreover, MRI measurements of the PHG-OFC circuit had an accuracy of 77.33% for the classification of amnestic mild cognitive impairment converters versus non-converters. Thus, the PHG-OFC circuit explains the neuroanatomical basis of visuospatial memory deficits in AD, thereby providing a potential predictor for AD progression and a promising interventional approach for AD.

The correlation between the electroencephalographic spectral analysis and salivary cortisol rhythm in insomnia.

OBJECTIVE: Insomnia is a common sleep disorder that affects many adults either transiently or chronically. This study aimed to establish whether there is a relationship between the electroencephalographic (EEG) spectral analysis and salivary cortisol levels in insomnia and compared to healthy controls. MATERIALS AND METHODS: This case-control study included 15 insomnia patients and 15 healthy control subjects. Insomnia was determined according to the International Classification of Headache Disorders III diagnostic criteria. The EEG data were collected and processed with MATLAB software. Blood and salivary samples were taken for hematological and biochemical measurements. Salivary cortisol levels were calculated and compared statistically with the healthy group. RESULTS: The mean age of the patients was 46.5 ± 11 years. The salivary cortisol levels at 18:00 and 24:00 were found higher in the insomnia than in the healthy subjects (respectively, 0.12 (0.11) µg/dl, 0.07 (0.02) µg/dl). But this difference was not statistically significant (p > 0.05). No significant difference was observed in the spectral analysis of patients between the frontal, central, and occipital channel (p > 0.05). However, in the correlation between the frontal channel spectral analysis and at the 24:00 salivary cortisol of patient and control group, DeltaGmax (p = 0.002), DeltaGmean (p = 0.019) and, in the correlation with 18:00 salivary cortisol DeltaGmax (p = 0.010), were positively correlated. CONCLUSION: In this study, no significant difference was found in spectral analysis and salivary cortisol levels in insomnia patients, but at 18:00 and 24:00, cortisol levels were correlated positively with theta and delta waves in EEG spectral analysis in some channels.

Functional connectivity of the right inferior frontal gyrus and orbitofrontal cortex in depression.

The orbitofrontal cortex extends into the laterally adjacent inferior frontal gyrus. We analyzed how voxel-level functional connectivity of the inferior frontal gyrus and orbitofrontal cortex is related to depression in 282 people with major depressive disorder (125 were unmedicated) and 254 controls, using FDR correction P < 0.05 for pairs of voxels. In the unmedicated group, higher functional connectivity was found of the right inferior frontal gyrus with voxels in the lateral and medial orbitofrontal cortex, cingulate cortex, temporal lobe, angular gyrus, precuneus, hippocampus and frontal gyri. In medicated patients, these functional connectivities were lower and toward those in controls. Functional connectivities between the lateral orbitofrontal cortex and the precuneus, posterior cingulate cortex, inferior frontal gyrus, ventromedial prefrontal cortex and the angular and middle frontal gyri were higher in unmedicated patients, and closer to controls in medicated patients. Medial orbitofrontal cortex voxels had lower functional connectivity with temporal cortex areas, the parahippocampal gyrus and fusiform gyrus, and medication did not result in these being closer to controls. These findings are consistent with the hypothesis that the orbitofrontal cortex is involved in depression, and can influence mood and behavior via the right inferior frontal gyrus, which projects to premotor cortical areas.

Nocturnal Hypoxemia Is Associated with Altered Parahippocampal Functional Brain Connectivity in Older Adults at Risk for Dementia.

BACKGROUND: Obstructive sleep apnea is associated with an increased risk of developing mild cognitive impairment and dementia. Intermittent nocturnal hypoxemia in obstructive sleep apnea is associated with brain changes in key regions that underpin memory. OBJECTIVE: To determine whether older adults with severe nocturnal hypoxemia would exhibit reduced functional connectivity within these regions, with associated deficits in memory. METHODS: Seventy-two participants 51 years and over underwent polysomnography with continuous blood oxygen saturation recorded via oximetry. The oxygen desaturation index (ODI, 3% dips in oxygen levels per hour) was the primary outcome measure. ODI was split into tertiles, with analyses comparing the lowest and highest tertiles (N = 48). Thirty-five of the 48 participants from these two tertiles had mild cognitive impairment. Participants also underwent resting-state fMRI and comprehensive neuropsychological, medical, and psychiatric assessment. RESULTS: The highest ODI tertile group demonstrated significantly reduced connectivity between the left and right parahippocampal cortex, relative to the lowest ODI tertile group (t(42) = -3.26, p = 0.041, beta = -1.99).The highest ODI tertile group also had poorer working memory performance. In the highest ODI tertile group only, higher left-right parahippocampal functional connectivity was associated with poorer visual memory recall (between-groups z = -2.93, p = 0.0034). CONCLUSIONS: Older adults with severe nocturnal hypoxemia demonstrate impaired functional connectivity in medial temporal structures, key regions involved in sleep memory processing and implicated in dementia pathophysiology. Oxygen desaturation and functional connectivity in these individuals each relate to cognitive performance. Research is now required to further elucidate these findings.

Altered brain activities associated with cue reactivity during forced break in subjects with Internet gaming disorder.

BACKGROUND: Studies have proven that forced break can elicit strong psychological cravings for addictive behaviors. This phenomenon could create an excellent situation to study the neural underpinnings of addiction. The current study explores brain features during a cue-reactivity task in Internet gaming disorder (IGD) when participants were forced to stop their gaming behaviors. METHODS: Forty-nine IGD subjects and forty-nine matched recreational Internet game users (RGU) were asked to complete a cue-reactivity task when their ongoing gaming behaviors were forced to break. We compared their brain responses to gaming cues and tried to find specific features associated with IGD. RESULTS: Compared with RGU, the IGD subjects showed decreased activation in the anterior cingulate cortex (ACC), parahippocampal gyrus, and dorsolateral prefrontal cortex (DLPFC). Significant negative correlations were observed between self-reported gaming cravings and the baseline activation level (bate value) of the ACC, DLPFC, and parahippocampal gyrus. CONCLUSIONS: IGD subjects were unable to suppress their gaming cravings after unexpectedly forced break. This result could also explain why RGU subjects are able to play online games without developing dependence.

Scene construction impairments in frontotemporal dementia: Evidence for a primary hippocampal contribution.

The capacity to generate naturalistic three-dimensional and spatially coherent representations of the world, i.e., scene construction, is posited to lie at the heart of a wide range of complex cognitive endeavours. Clinical populations with selective damage to key nodes of a putative scene construction network of the brain have provided important insights regarding the contribution of medial temporal and prefrontal regions in this regard. Here, we explored the capacity for atemporal scene construction, and its associated neural substrates, in the behavioural-variant of frontotemporal dementia (bvFTD); a neurodegenerative brain disorder in which atrophy systematically erodes medial and lateral prefrontal cortices with variable medial temporal lobe involvement. Nineteen bvFTD patients were compared to 18 typical Alzheimer's Disease (AD), and 25 healthy older Control participants on a scene construction task. Relative to Controls, both patient groups displayed marked impairments in generating contextually detailed and spatially coherent scenes, with bvFTD indistinguishable from AD patients across the majority of task metrics. Voxel-based morphometry, based on structural brain MRI, revealed divergent neural substrates of scene construction performance in each patient group. Despite widespread medial and lateral prefrontal atrophy, the capacity to generate richly detailed and spatially coherent scenes in bvFTD was found to rely predominantly upon the integrity of right medial temporal structures, including the hippocampus and parahippocampal gyrus. Scene construction impairments in AD, by contrast, hinged upon the integrity of posterior parietal brain regions. Our findings in bvFTD resonate with a large body of work implicating the right hippocampus in the construction of spatially integrated scene imagery. How these impairments relate to changes in autobiographical memory and prospection in bvFTD will be an important question for future studies to address.

Effect-size seed-based d mapping of resting-state fMRI for persistent insomnia disorder.

BACKGROUND: Recently, several functional neuroimaging studies have been conducted in patients with persistent insomnia disorder, but these studies have yielded diverse findings. We aimed to identify convergence in function across the heterogeneity of patients, modalities, and methods for insomnia disorder by performing a quantitative coordinate-based meta-analysis. MATERIALS AND METHODS: We performed a quantitative, voxel-wise meta-analysis of resting-state fMRI studies using seed-based d mapping to find convergence of functional alterations in persistent insomnia disorder. RESULTS: We included 28 studies comprising 287 peak foci involving 951 patients with insomnia disorder and 884 healthy controls. Patients with persistent insomnia disorder showed that increased activity was more frequently reported in right parahippocampal gyrus (p < 0.001) and left median cingulate/paracingulate gyri (p < 0.001); while decreased activity was more frequently reported in right cerebellum (p < 0.001) and left superior frontal gyrus/medial orbital (p < 0.001). CONCLUSION: The altered functional networks in patients with persistent insomnia disorder converge in median cingulate/paracingulate gyri and right parahippocampal gyrus with increased activity, and cerebellum and superior frontal gyrus/medial orbital with reduced activity. As a potential target in future, the identification of these altered or unbalanced networks is very important because they may be noninvasively rebalanced to sleep homeostasis by noninvasive brain stimulation methods.

Changes in brain activation related to visuo-spatial memory after real-time fMRI neurofeedback training in healthy elderly and Alzheimer's disease.

Cognitive decline is a symptom of healthy ageing and Alzheimer's disease. We examined the effect of real-time fMRI based neurofeedback training on visuo-spatial memory and its associated neuronal response. Twelve healthy subjects and nine patients of prodromal Alzheimer's disease were included. The examination spanned five days (T1-T5): T1 contained a neuropsychological pre-test, the encoding of an itinerary and a fMRI-based task related that itinerary. T2-T4 hosted the real-time fMRI neurofeedback training of the parahippocampal gyrus and on T5 a post-test session including encoding of another itinerary and a subsequent fMRI-based task were done. Scores from neuropsychological tests, brain activation and task performance during the fMRI-paradigm were compared between pre and post-test as well as between healthy controls and patients. Behavioural performance in the fMRI-task remained unchanged, while cognitive testing showed improvements in visuo-spatial memory performance. Both groups displayed task-relevant brain activation, which decreased in the right precentral gyrus and left occipital lobe from pre to post-test in controls, but increased in the right occipital lobe, middle frontal gyrus and left frontal lobe in the patient group. While results suggest that the training has affected brain activation differently between controls and patients, there are no pointers towards a behavioural manifestation of these changes. Future research is required on the effects that can be induced using real-time fMRI based neurofeedback training and the required training duration to elicit broad and lasting effects.

Limbic Hyperactivity in Response to Emotionally Neutral Stimuli in Schizophrenia: A Neuroimaging Meta-Analysis of the Hypervigilant Mind.

OBJECTIVE: It has long been assumed that paranoid ideation may stem from an aberrant limbic response to threatening stimuli. However, results from functional neuroimaging studies using negative emotional stimuli have failed to confirm this assumption. One of the potential reasons for the lack of effect is that study participants with psychosis may display aberrant brain responses to neutral material rather than to threatening stimuli. The authors conducted a functional neuroimaging meta-analysis to test this hypothesis. METHODS: A literature search was performed with PubMed, Google Scholar, and Embase to identify functional neuroimaging studies examining brain responses to neutral material in patients with psychosis. A total of 23 studies involving schizophrenia patients were retrieved. Using t-maps of peak coordinates to calculate effect sizes, a random-effects model meta-analysis was performed with the anisotropic effect-size version of Seed-based d Mapping software. RESULTS: In schizophrenia patients relative to healthy control subjects, increased activations were observed in the left and right amygdala and parahippocampus and the left putamen, hippocampus, and insula in response to neutral stimuli. CONCLUSIONS: Given that several limbic regions were found to be more activated in schizophrenia patients than in control subjects, the results of this meta-analysis strongly suggest that these patients confer aberrant emotional significance to nonthreatening stimuli. In theory, this abnormal brain reactivity may fuel delusional thoughts. Studies are needed in individuals at risk of psychosis to determine whether aberrant limbic reactivity to neutral stimuli is an early neurofunctional marker of psychosis vulnerability.

Decreased static and increased dynamic global signal topography in major depressive disorder.

Major depressive disorder (MDD) has been linked to imbalanced communication among large-scale brain networks. However, the details of altered large-scale coordination of MDD remains unknown. To explore the altered large-scale functional organization in MDD. We used static and dynamic global signal (GS) topography, which are data-driven methods to explore altered relationship between global and local neuronal activities in MDD. Sixty three MDD patients and matched 63 healthy controls (HCs) were recruited in current study. Patients with MDD presented decreased static GS topography in bilateral parahippocampal gyrus and hippocampus gyrus. Meanwhile, patients with MDD presented increased variability of dynamic GS topography in the right ventromedial prefrontal cortex. This result may reflect the decreased and unstable whole brain functional coherence in MDD. The decreased static GS topography in the right parahippocampal gyrus was correlated with psychomotor retardation in patients with MDD. Our results presented that the altered static and dynamic GS topography can provide distinct evidence on the physiological mechanisms of MDD.

The CD33 genotype associated cognitive performance was bidirectionally modulated by intrinsic functional connectivity in the Alzheimer's disease spectrum.

CD33 is a susceptibility locus for late-onset Alzheimer's disease (AD). However, how the neural mechanism of CD33 affects cognition in the AD spectrum population remains unclear. We aimed to investigate the primary and interactive effects of the CD33 (rs3865444) genotype on brain function in patients with AD using global functional connectivity density (gFCD) mapping via resting-state functional magnetic resonance imaging. Furthermore, we used a conditional process analysis to identify the relationship among the CD33 genotype, gFCD, and cognition performance across the AD spectrum population. Compared to cognitively normal (CN) and mild cognitively impaired (MCI) subjects, patients with AD showed higher gFCD in the default mode network, and the CD33 genotype primarily influenced brain function in the fronto-striatal circuit. Importantly, an interaction between the CD33 genotype and AD was observed in the parahippocampal gyrus. During disease progression, the gFCD trajectories of the CD33 A + allele gradually decreased, whereas those of the CD33 CC allele displayed an inverted U-shaped curve. Furthermore, gFCD in the dorsal anterior cingulate cortex positively mediated the relationship between the CD33 genotype and cognition, while gFCD in the precuneus bidirectionally moderated the mediation in the AD spectrum. These findings provide new insights into the neural mechanisms underlying the influence of the CD33 genotype on cognitive performance and highlight the importance of precise therapeutic strategies for high-risk AD populations.