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Sleep disturbances (SD) are common in major depressive disorder (MDD) patients. Brain functional asymmetry is crucial for understanding MDD pathophysiology. Previous studies using the parameter of asymmetry (PAS) approach have found brain functional asymmetry disruption in MDD. However, this has not been explored in MDD patients with SD. This study examined 26 MDD patients with SD, 34 MDD patients without SD, and 34 healthy controls using resting-state functional magnetic resonance imaging scans. SD symptoms were quantified using the 17-item Hamilton Rating Scale for Depression. PAS approach was used to evaluate functional asymmetry. MDD patients with SD displayed increased PAS in the left middle frontal gyrus (MFG)/inferior frontal gyrus (IFG) and decreased PAS in the left parahippocampal gyrus (PHG) compared to MDD patients without SD. Increased PAS in the left MFG/IFG was positively correlated with SD severity, and a negative correlation was found between decreased PAS in the left PHG and SD scores in all MDD patients. Receiver operating characteristic analysis indicated that increased PAS in the left MFG/IFG and decreased PAS in the left PHG may serve as potential neuroimaging markers to differentiate MDD patients with SD from those without SD with Area Under Curve values of 0.8157 and 0.8068, respectively. These results highlighted that increased PAS in the left MFG/IFG and decreased PAS in the left PHG may be considered a prominent feature associated with SD symptoms of MDD patients, potentially serving as imaging markers to discriminate between MDD patients with and without SD., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the medical research ethics committee of the Second Xiangya Hospital of Central South University. All the procedures described herein comply with the Helsinki Declaration of 2013. Each participant provided informed consent before enrollment. Consent for publication: All authors have read and approved the submission. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Previous studies have revealed functional changes within the cerebral hemispheres of patients with SLE; however the changes between cerebral hemispheres are still unknown. The present study aimed to explore the functional and structural changes between bilateral hemispheres using functional MRI and find their relationship with cognition in patients with SLE., Methods: 54 patients with SLE and 32 age-matched and sex-matched healthy controls (HCs) underwent MRI scanning and neuropsychological testing, and clinical data was collected in patients with SLE. Voxel-mirrored homotopic connectivity (VMHC) values and grey matter volume were calculated for all subjects. Correlation analysis was established to determine the relationship between VMHC values, grey matter volume and cognitive scores, blood biochemical markers in patients with SLE., Results: Compared with HCs, patients with SLE showed increased VMHC values in the insula and parahippocampal gyrus, while grey matter volume were reduced in these regions. Correlation analysis demonstrated that the increased VMHC values in insula was negatively correlated with decreased orientation function and positively correlated with decreased attention function. The grey matter volume in insula was negatively correlated with decreased attention and abstraction. The VMHC values and grey matter volume in insula and parahippocampal gyrus were negatively associated with lupus-specific antibodies., Conclusion: The structural and functional changes of insula and parahippocampal gyrus might be potential neuroimaging markers, and specific antibodies associated with lupus might be involved in the pathophysiological mechanisms of brain dysfunction., Trial Registration Number: NCT06226324., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Prior studies have reported inconsistent results regarding the relationships between the integrity of the fornix and parahippocampal cingulum and both memory performance and longitudinal change in performance. In the present study, we examined associations in a sample of cognitively healthy older adults between free water-corrected fractional anisotropy (FA) metrics derived from the fornix and cingulum, baseline memory performance, and 3-year memory change. Neither fornix nor cingulum FA correlated with memory performance at baseline. By contrast, FA of each tract was predictive of memory change, such that greater FA was associated with less longitudinal decline. These associations remained significant after controlling for FA of other white matter tracts and for performance in other cognitive domains. Furthermore, fornix and cingulum FA explained unique variance in memory change. These results suggest that free water-corrected measures of fornix and parahippocampal cingulum integrity are reliable predictors of future memory change in cognitively healthy older adults. The findings for the fornix in particular highlight the utility of correcting for free water when estimating diffusion tensor imaging metrics of white matter integrity., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., (© 2024. The Author(s).)

Contextual features are integral to episodic memories; yet, we know little about context effects on pattern separation, a hippocampal function promoting orthogonalization of overlapping memory representations. Recent studies suggested that various extrahippocampal brain regions support pattern separation; however, the specific role of the parahippocampal cortex-a region involved in context representation-in pattern separation has not yet been studied. Here, we investigated the contribution of the parahippocampal cortex (specifically, the parahippocampal place area) to context reinstatement effects on mnemonic discrimination, using functional magnetic resonance imaging. During scanning, participants saw object images on unique context scenes, followed by a recognition task involving the repetitions of encoded objects or visually similar lures on either their original context or a lure context. Context reinstatement at retrieval improved item recognition but hindered mnemonic discrimination. Crucially, our region of interest analyses of the parahippocampal place area and an object-selective visual area, the lateral occipital cortex indicated that while during successful mnemonic decisions parahippocampal place area activity decreased for old contexts compared to lure contexts irrespective of object novelty, lateral occipital cortex activity differentiated between old and lure objects exclusively. These results imply that pattern separation of contextual and item-specific memory features may be differentially aided by scene and object-selective cortical areas., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and prone to the accumulation of certain neuropathologies such as Alzheimer's disease neurofibrillary tau tangles. The MTL cortex is composed of several subregions which differ in their functional and cytoarchitectonic features. As neuroanatomical schools rely on different cytoarchitectonic definitions of these subregions, it is unclear to what extent their delineations of MTL cortex subregions overlap. Here, we provide an overview of cytoarchitectonic definitions of the entorhinal and parahippocampal cortices as well as Brodmann areas (BA) 35 and 36, as provided by four neuroanatomists from different laboratories, aiming to identify the rationale for overlapping and diverging delineations. Nissl-stained series were acquired from the temporal lobes of three human specimens (two right and one left hemisphere). Slices (50 μm thick) were prepared perpendicular to the long axis of the hippocampus spanning the entire longitudinal extent of the MTL cortex. Four neuroanatomists annotated MTL cortex subregions on digitized slices spaced 5 mm apart (pixel size 0.4 μm at 20× magnification). Parcellations, terminology, and border placement were compared among neuroanatomists. Cytoarchitectonic features of each subregion are described in detail. Qualitative analysis of the annotations showed higher agreement in the definitions of the entorhinal cortex and BA35, while the definitions of BA36 and the parahippocampal cortex exhibited less overlap among neuroanatomists. The degree of overlap of cytoarchitectonic definitions was partially reflected in the neuroanatomists' agreement on the respective delineations. Lower agreement in annotations was observed in transitional zones between structures where seminal cytoarchitectonic features are expressed less saliently. The results highlight that definitions and parcellations of the MTL cortex differ among neuroanatomical schools and thereby increase understanding of why these differences may arise. This work sets a crucial foundation to further advance anatomically-informed neuroimaging research on the human MTL cortex., (© 2024 The Authors. Hippocampus published by Wiley Periodicals LLC.)

Face perception is a complex process that involves highly specialized procedures and mechanisms. Investigating into face perception can help us better understand how the brain processes fine-grained, multidimensional information. This research aimed to delve deeply into how different dimensions of facial information are represented in specific brain regions or through inter-regional connections via an implicit face recognition task. To capture the representation of various facial information in the brain, we employed support vector machine decoding, functional connectivity, and model-based representational similarity analysis on fMRI data, resulting in the identification of three crucial findings. Firstly, despite the implicit nature of the task, emotions were still represented in the brain, contrasting with all other facial information. Secondly, the connection between the medial amygdala and the parahippocampal gyrus was found to be essential for the representation of facial emotion in implicit tasks. Thirdly, in implicit tasks, arousal representation occurred in the parahippocampal gyrus, while valence depended on the connection between the primary visual cortex and the parahippocampal gyrus. In conclusion, these findings dissociate the neural mechanisms of emotional valence and arousal, revealing the precise spatial patterns of multidimensional information processing in faces., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2024. Published by Elsevier Inc.)

The hippocampus and parahippocampal gyrus have been implicated as part of a tinnitus network by a number of studies. These structures are usually considered in the context of a "limbic system," a concept typically invoked to explain the emotional response to tinnitus. Despite this common framing, it is not apparent from current literature that this is necessarily the main functional role of these structures in persistent tinnitus. Here, we highlight a different role that encompasses their most commonly implicated functional position within the brain-that is, as a memory system. We consider tinnitus as an auditory object that is held in memory, which may be made persistent by associated activity from the hippocampus and parahippocampal gyrus. Evidence from animal and human studies implicating these structures in tinnitus is reviewed and used as an anchor for this hypothesis. We highlight the potential for the hippocampus/parahippocampal gyrus to facilitate maintenance of the memory of the tinnitus percept via communication with auditory cortex, rather than (or in addition to) mediating emotional responses to this percept., (© 2024 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Procrastination has adverse effects on personal growth and social development. Behavior research has found reward sensitivity is positively correlated with procrastination. However, it remains unclear that the neural substrates underlie the relationship between reward sensitivity and procrastination. To address this issue, the present study used voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) analyses to investigate the neural substrates underlying the association with reward sensitivity and procrastination in two independent samples (N1 = 388, N2 = 330). In Sample 1, the behavioral result indicated reward sensitivity was positively correlated with procrastination. Moreover, the VBM analysis showed that reward sensitivity was positively associated with the gray matter volume (GMV) of the right parahippocampal gyrus. Furthermore, the RSFC result found reward sensitivity was negatively associated with the functional connectivity of the right parahippocampal gyrus-precuneus. Crucially, the mediation analysis revealed that functional connectivity of the right parahippocampal gyrus-precuneus mediated the relationship between reward sensitivity and procrastination. To verify the robustness of the results, confirmatory analysis was carried out in Sample 2. The results of Sample 1 (i.e., the behavioral, VBM, RSFC, and mediation results) can be verified in Sample 2. In brief, these findings suggested that the functional connectivity of the right parahippocampal gyrus-precuneus involved in reward impulsive control could modulate the relationship between reward sensitivity and procrastination, which is the first to reveal the neural underpinning of the association between reward sensitivity and procrastination., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and Objective: Amyotrophic lateral sclerosis (ALS) is a progressive motor and extra-motor neurodegenerative disease. This systematic review aimed to examine MRI biomarkers and neuropsychological assessments of the hippocampal and parahippocampal regions in patients with ALS., Methods: A systematic review was conducted in the Scopus and PubMed databases for studies published between January 2000 and July 2023. The inclusion criteria were (1) MRI studies to assess hippocampal and parahippocampal regions in ALS patients, and (2) studies reporting neuropsychological data in patients with ALS., Results: A total of 46 studies were included. Structural MRI revealed hippocampal atrophy, especially in ALS-FTD, involving specific subregions (CA1, dentate gyrus). Disease progression and genetic factors impacted atrophy patterns. Diffusion tensor imaging (DTI) showed increased mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and decreased fractional anisotropy (FA) in the hippocampal tracts and adjacent regions, indicating loss of neuronal and white matter integrity. Functional MRI (fMRI) revealed reduced functional connectivity (FC) between the hippocampus, parahippocampus, and other regions, suggesting disrupted networks. Perfusion MRI showed hypoperfusion in parahippocampal gyri. Magnetic resonance spectroscopy (MRS) found changes in the hippocampus, indicating neuronal loss. Neuropsychological tests showed associations between poorer memory and hippocampal atrophy or connectivity changes. CA1-2, dentate gyrus, and fimbria atrophy were correlated with worse memory., Conclusions: The hippocampus and the connected regions are involved in ALS. Hippocampal atrophy disrupted connectivity and metabolite changes correlate with cognitive and functional decline. Specific subregions can be particularly affected. The hippocampus is a potential biomarker for disease monitoring and prognosis., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Visuospatial perception is often impaired in people with Alzheimer's disease (AD). Because visuospatial information is thought to be processed in the visual dorsal stream, it is believed that brain activities in the dorsal stream will be altered in AD patients. In this study, we investigated whether regional brain activity related to visuospatial perception were associated with AD progression markers. An optic-flow task, which activates the dorsal stream associated with visuospatial perception, was performed, and the brain activities evoked by the task were evaluated using magnetoencephalography (MEG). First, we evaluated the responses to optic-flow stimuli in 21 cognitively unimpaired participants and determined the regions of interest (ROIs) where optic-flow activities were activated. Task-related activations were observed in 14 cortical regions including the dorsal stream: the right and left medial ventral occipital cortex (MVOcC), lateral occipital cortex (LOcC), precuneus (Pcun), inferior parietal lobule (IPL), superior parietal lobule (SPL), posterior superior temporal sulcus (pSTS), and fusiform gyri (FuG). Next, we performed correlation analyses between task-related activity in each ROI and two AD progression markers, global amyloid burden and parahippocampal gyrus (PHG) volume, for 25 participants who underwent amyloid positron emission tomography (PET) scans. We found that the global amyloid burden was negatively correlated with task-related activity in the left MVOcC and right SPL [r = -0.488 (p = 0.013) and r = -0.421 (p = 0.038), respectively]. Furthermore, significant positive correlations were observed between PHG volume and task-related activity in both the left and right SPL [r = 0.500 (p = 0.011) and r = 0.549 (p = 0.005), respectively]. Since the SPL is known to be responsible for visuospatial perception, these results suggest that MEG neuronal activity of patients performing the optic-flow activity can detect changes in brain activity associated with visuospatial impairment related to AD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ST, KK, HM, YM and TA are employees of Ricoh Company, Ltd. The authors declare that no other competing interests exist. The other authors have no competing financial conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Brain entropy reveals complexity and irregularity of brain, and it has been proven to reflect brain complexity alteration in disease states. Previous studies found that bipolar disorder adolescents showed cognitive impairment. The relationship between complexity of brain neural activity and cognition of bipolar II disorder (BD-II) adolescents remains unclear., Methods: Nineteen BD-II patients (14.63 ±1.57 years old) and seventeen age-gender matched healthy controls (HCs) (14.18 ± 1.51 years old) were enlisted. Entropy values of all voxels of the brain in resting-state functional MRI data were calculated and differences of them between BD-II and HC groups were evaluated. After that, correlation analyses were performed between entropy values of brain regions showing significant entropy differences and clinical indices in BD-II adolescents., Results: Significant differences were found in scores of immediate visual reproduction subtest (VR-I, p = 0.003) and Stroop color-word test (SCWT-1, p = 0.015; SCWT-2, p = 0.004; SCWT-3, p = 0.003) between the two groups. Compared with HCs, BD-II adolescents showed significant increased brain entropy in right parahippocampal gyrus and right inferior occipital gyrus. Besides, significant negative correlations between brain entropy values of right parahippocampal gyrus, right inferior occipital gyrus and immediate visual reproduction subtest scores were observed in BD-II adolescents., Conclusions: The findings of the present study suggested that the disrupted function of corticolimbic system is related with cognitive abnormality of BD-II adolescents. And from the perspective temporal dynamics of brain system, the current study, brain entropy may provide available evidences for understanding the underlying neural mechanism in BD-II adolescents., (© 2023. The Author(s).)

Parahippocampal cortex (PHC) is a vital neural bases in spatial navigation. However, its functional role is still unclear. "Contextual hypothesis," which assumes that the PHC participates in processing the spatial association between the landmark and destination, provides a potential answer to the question. Nevertheless, the hypothesis was previously tested using the picture categorization task, which is indirectly related to spatial navigation. By now, study is still needed for testing the hypothesis with a navigation-related paradigm. In the current study, we tested the hypothesis by an fMRI experiment in which participants performed a distance estimation task in a virtual environment under three different conditions: landmark free (LF), stable landmark (SL), and ambiguous landmark (AL). By analyzing the behavioral data, we found that the presence of an SL improved the participants' performance in distance estimation. Comparing the brain activity in SL-versus-LF contrast as well as AL-versus-LF contrast, we found that the PHC was activated by the SL rather than by AL when encoding the distance. This indicates that the PHC is elicited by strongly associated context and encodes the landmark reference for distance perception. Furthermore, accessing the representational similarity with the activity of the PHC across conditions, we observed a high similarity within the same condition but low similarity between conditions. This result indicated that the PHC sustains the contextual information for discriminating between scenes. Our findings provided insights into the neural correlates of the landmark information processing from the perspective of contextual hypothesis., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Risk-taking differs between humans, and is associated with the personality measures of impulsivity and sensation-seeking. To analyse the brain systems involved, self-report risk-taking, resting state functional connectivity, and related behavioral measures were analyzed in 18,740 participants of both sexes from the UK Biobank. Functional connectivities of the medial orbitofrontal cortex, ventromedial prefrontal cortex (VMPFC), and the parahippocampal areas were significantly higher in the risk-taking group (p < 0.001, FDR corrected). The risk-taking measure was validated in that it was significantly associated with alcohol drinking amount (r = 0.08, p = 5.1×10 -28 ), cannabis use (r = 0.12, p = 6.0×10 -66 ), and anxious feelings (r = -0.12, p = 7.6× -98 ). The functional connectivity findings were cross-validated in two independent datasets. The higher functional connectivity of the medial orbitofrontal cortex and VMPFC included higher connectivity with the anterior cingulate cortex, which provides a route for these reward-related regions to have a greater influence on action in risk-taking individuals. In conclusion, the medial orbitofrontal cortex, which is involved in reward value and pleasure, was found to be related to risk-taking, which is associated with impulsivity. An implication is that risk-taking is driven by specific orbitofrontal cortex reward systems, and is different for different rewards which are represented differently in the brains of different individuals. This is an advance in understanding the bases and mechanisms of risk-taking in humans, given that the orbitofrontal cortex, VMPFC and anterior cingulate cortex are highly developed in humans, and that risk-taking can be reported in humans., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aim: Problematic mobile phone use (PMPU) is prevalent and increases the risk for a variety of health problems. However, few studies have explored the neural mechanisms that might render adolescents more or less vulnerable. Here, we aimed to identify whether PMPU is associated with depressive symptoms and whether this relationship is moderated by intrinsic functional connectivity (iFC) which is associated with PMPU., Methods: In this longitudinal study, we included 238 students (mean age = 19.05, SD = 0.81) that came from a university in Hefei, China. They all finished MRI scans at baseline and completed questionnaires both at baseline and 1 year later. A self-rating questionnaire for adolescent problematic mobile phone use and depression anxiety stress scale-21 were used to assess PMPU and depressive symptoms. We first assessed the relationship between PMPU and depressive symptoms using an autoregressive cross-lagged model. Then, we detected the brain regions that were associated with PMPU. Moreover, the neuroimaging results were extracted to explore whether the iFC of these brain regions moderated the relationship between PMPU and depression., Results: Consistent with our hypotheses, PMPU was positively associated with depressive symptoms, and the relationship between PMPU and depressive symptoms was moderated by iFC of the left parahippocampal gyrus-right middle temporal gyrus both at baseline and after 1 year (β = 0.554, P = 0.003; β = 0.463, P = 0.016, respectively)., Conclusions: These results advance the understanding of PMPU and suggest that iFC of the left parahippocampal gyrus-right middle temporal gyrus may be a neurobiological contributor to its relationship with depressive symptoms.

Background: Alterations of brain signal complexity may reflect brain functional abnormalities. In adolescent bipolar disorder (ABD) distribution of brain regions showing abnormal complexity in different mood states remains unclear. We aimed to analyze brain entropy (BEN) alteration of functional magnetic resonance imaging (fMRI) signal to observe spatial distribution of complexity in ABD patients, as well as the relationship between this variation and clinical variables., Methods: Resting-state fMRI data were acquired from adolescents with bipolar disorder (BD) who were in manic (n = 19) and euthymic (n = 20) states, and from healthy controls (HCs, n = 17). The differences in BEN among the three groups, and their associations with clinical variables, were examined., Results: Compared to HCs, manic and euthymic ABD patients showed increased BEN in right parahippocampal gyrus (PHG) and left dorsolateral prefrontal cortex (DLPFC). There was no significant difference of BEN between the manic and the euthymic ABD groups. In manic ABD patients, right PHG BEN exhibited significantly positive relationship with episode times., Conclusions: Increased BEN in right PHG and left DLPFC in ABD patients may cause dysfunction of corticolimbic circuitry which is important to emotional processing and cognitive control. The positive correlation between PHG BEN and episode times of manic ABD patients further expressed a close association between brain complexity and clinical symptoms. From the perspective of brain temporal dynamics, the present study complements previous findings that have reported corticolimbic dysfunction as an important contributor to the pathophysiology of BD. BEN may provide valuable evidences for understanding the underlying mechanism of ABD., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims/introduction: We aimed to examine the association between diabetes-related parameters and hippocampal and parahippocampal gyrus atrophy (HPGA) in patients with type 2 diabetes mellitus to elucidate the risk factors for HPGA, which is often accompanied by Alzheimer's disease., Materials and Methods: A total of 137 patients aged ≥50 years with type 2 diabetes mellitus (mean age 67.8 ± 9.8 years) underwent brain magnetic resonance imaging scans and comprehensive health examinations. We measured the volume of interest - a portion of the inner temporal lobe that includes the hippocampus, amygdala and entorhinal cortex (frontal part of the parahippocampal gyrus) - using the voxel-based specific regional analysis system for Alzheimer's disease in each patient. The diabetes-related parameters included glycated hemoglobin, fasting plasma glucose, C-peptide (CPR) index (serum CPR / fasting plasma glucose × 100) and duration of diabetes., Results: The mean glycated hemoglobin was 9.3 ± 2.2%, the median CPR index was 1.29 (interquartile range 0.85-1.74) and the median duration of diabetes was 10 years (interquartile range 3-20 years). The severity score of volume of interest atrophy was >1.0 in 36 patients. Using multivariate logistic regression analysis, we found that age (odds ratio 1.09, 95% confidence interval 1.02-1.15) and CPR index (odds ratio 0.451, 95% confidence interval 0.216-0.940) were significantly associated with HPGA., Conclusions: Lower insulin secretion was significantly associated with HPGA in patients with type 2 diabetes mellitus. The results of this study support the hypothesis that insulin-signaling abnormalities are involved in the pathophysiology of Alzheimer's disease., (© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Repetitive transcranial magnetic stimulation (rTMS) of the inferior parietal cortex (IPC) increases resting-state functional connectivity (rsFC) of the hippocampus with the precuneus and other posterior cortical areas and causes proportional improvement of episodic memory. The anatomical pathway(s) responsible for the propagation of these effects from the IPC is unknown and may not be direct. In order to assess the relative contributions of candidate pathways from the IPC to the MTL via the parahippocampal cortex and precuneus, to the effects of rTMS on rsFC and memory improvement, we used diffusion tensor imaging to measure the extent to which individual differences in fractional anisotropy (FA) in these pathways accounted for individual differences in response. FA in the IPC-parahippocampal pathway and several MTL pathways predicted changes in rsFC. FA in both parahippocampal and hippocampal pathways was related to changes in episodic, but not procedural, memory. These results implicate pathways to the MTL in the enhancing effect of parietal rTMS on hippocampal rsFC and memory., (Published by Elsevier Inc.)

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., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Landmark objects are points of reference that can anchor one's internal cognitive map to the external world while navigating. They are especially useful in indoor environments where other cues such as spatial geometries are often similar across locations. We used functional magnetic resonance imaging (fMRI) and multivariate pattern analysis (MVPA) to understand how the spatial significance of landmark objects is represented in the human brain. Participants learned the spatial layout of a virtual building with arbitrary objects as unique landmarks in each room during a navigation task. They were scanned while viewing the objects before and after learning. MVPA revealed that the neural representation of landmark objects in the right parahippocampal place area (rPPA) and the hippocampus transformed systematically according to their locations. Specifically, objects in different rooms became more distinguishable than objects in the same room. These results demonstrate that rPPA and the hippocampus encode the spatial significance of landmark objects in indoor spaces., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Surprising scenarios can have different behavioural and neuronal consequences depending on the violation of the expectation. On the one hand, previous research has shown that the omission of a visual stimulus results in a robust cortical response representing that missing stimulus, a so-called negative prediction error. On the other hand, a large amount of studies revealed positive prediction error signals, entailing an increased neural response that can be attributed to the experience of a surprising, unexpected stimulus. However, there has been no evidence, so far, regarding how and when these prediction error signals co-occur. Here, we argue that the omission of an expected stimulus can and often does coincide with the appearance of an unexpected one. Therefore, we investigated whether positive and negative prediction error signals evoked by unpredicted cross-category stimulus transitions would temporally coincide during a speeded forced-choice fMRI paradigm. Foremost, our findings provide evidence of a behavioural effect regarding the facilitation of responses linked to expected stimuli. In addition, we obtained evidence for negative prediction error signals as seen in differential activation of FFA and PPA during unexpected place and face trials, respectively. Lastly, a psychophysiological interaction analysis revealed evidence for positive prediction error signals represented by context-dependent functional coupling between the right IFG and FFA or PPA, respectively, implicating a network that updates the internal representation after the appearance of an unexpected stimulus through involvement of this frontal area. The current results are consistent with a predictive coding account of cognition and underline the importance of considering the potential dual nature of expectation violations. Furthermore, our results put forward that positive and negative prediction error signalling can be directly linked to regions associated with the processing of different stimulus categories., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-β and α-synuclein pathology were rated on a scale of 0 (absent)-3 (severe) in the hippocampus and entorhinal cortex (ERC) of 58 individuals with and without neurodegenerative diseases (median age 75.0 years, 60.3% male). Thickness measurements in ERC, Brodmann Area (BA) 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare (SRLM) were derived from 0.2 × 0.2 × 0.2 mm 3 post-mortem MRI scans of excised MTL specimens from the contralateral hemisphere using a semi-automated approach. Spearman's rank correlations were performed between neurodegenerative pathologies and thickness, correcting for age, sex and hemisphere, including all four proteinopathies in the model. We found significant associations of (1) TDP-43 with thickness in all subregions (r =  - 0.27 to r =  - 0.46), and (2) tau with BA35 (r =  - 0.31) and SRLM thickness (r =  - 0.33). In amyloid-β and TDP-43 negative cases, we found strong significant associations of tau with ERC (r =  - 0.40), BA35 (r =  - 0.55), subiculum (r =  - 0.42) and CA1 thickness (r =  - 0.47). This unique dataset shows widespread MTL atrophy in relation to TDP-43 pathology and atrophy in regions affected early in Braak stageing and tau pathology. Moreover, the strong association of tau with thickness in early Braak regions in the absence of amyloid-β suggests a role of Primary Age-Related Tauopathy in neurodegeneration., (© 2021. The Author(s).)

Confidence in our retrieved memories, that is, retrospective confidence, is a metamemory process we perform daily. There is an abundance of applied research focusing on the metamemory judgments and very diverse studies including a wide range of clinical populations. However, the neural correlates that support its functioning are not well defined impeding the implementation of noninvasive neuromodulatory clinical interventions. To address the neural basis of metamemory judgments, we ran a meta-analysis, where we used the activation likelihood estimation method on the 19 eligible functional magnetic resonance imaging studies. The main analysis of retrospective confidence revealed concordant bilateral activation in the parahippocampal gyrus, left middle frontal gyrus, and right amygdala. We also run an analysis between the two extreme levels of confidence, namely, high and low. This additional analysis was exploratory, since the minimum amount of articles reporting these two levels was not reached. Activations for the exploratory high > low confidence subtraction analysis were the same as observed in the main analysis on retrospective confidence, whereas the exploratory low > high subtraction showed distinctive activations of the right precuneus. The involvement of the right precuneus emphasizes its role in the evaluation of low confidence memories, as suggested by previous studies. Overall, our study contributes to a better understanding of the specific brain structures involved in confidence evaluations. Better understanding of the neural basis of metamemory might eventually lead to designing more precise neuromodulatory interventions, significantly improving treatment of patients suffering from metamemory problems., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Despite over two decades of research on the neural mechanisms underlying human visual scene, or place, processing, it remains unknown what exactly a "scene" is. Intuitively, we are always inside a scene, while interacting with the outside of objects. Hence, we hypothesize that one diagnostic feature of a scene may be concavity, portraying "inside", and predict that if concavity is a scene-diagnostic feature, then: 1) images that depict concavity, even non-scene images (e.g., the "inside" of an object - or concave object), will be behaviorally categorized as scenes more often than those that depict convexity, and 2) the cortical scene-processing system will respond more to concave images than to convex images. As predicted, participants categorized concave objects as scenes more often than convex objects, and, using functional magnetic resonance imaging (fMRI), two scene-selective cortical regions (the parahippocampal place area, PPA, and the occipital place area, OPA) responded significantly more to concave than convex objects. Surprisingly, we found no behavioral or neural differences between images of concave versus convex buildings. However, in a follow-up experiment, using tightly-controlled images, we unmasked a selective sensitivity to concavity over convexity of scene boundaries (i.e., walls) in PPA and OPA. Furthermore, we found that even highly impoverished line drawings of concave shapes are behaviorally categorized as scenes more often than convex shapes. Together, these results provide converging behavioral and neural evidence that concavity is a diagnostic feature of visual scenes., (Copyright © 2021. Published by Elsevier Inc.)

Background: The parahippocampal gyrus is understood to have a role in high cognitive functions including memory encoding and retrieval and visuospatial processing. A detailed understanding of the exact location and nature of associated white tracts could significantly improve postoperative morbidity related to declining capacity. Through diffusion tensor imaging-based fiber tracking validated by gross anatomic dissection as ground truth, we have characterized these connections based on relationships to other well-known structures., Methods: Diffusion imaging from the Human Connectome Project for 10 healthy adult controls was used for tractography analysis. We evaluated the parahippocampal gyrus as a whole based on connectivity with other regions. All parahippocampal gyrus tracts were mapped in both hemispheres, and a lateralization index was calculated with resultant tract volumes., Results: We identified 2 connections of the parahippocampal gyrus: inferior longitudinal fasciculus and cingulum. Lateralization of the cingulum was detected (P < 0.05)., Conclusions: The parahippocampal gyrus is an important center for memory processing. Subtle differences in executive functioning following surgery for limbic tumors may be better understood in the context of the fiber-bundle anatomy highlighted by this study., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Early course schizophrenia is associated with reduced gray matter. The specific structures affected first and how deficits impact symptoms and cognition remain unresolved. We used the Human Connectome Project multimodal parcellation (HCP-MMP) to precisely identify cortical areas and investigate thickness abnormalities in discovery and replication samples of first-episode schizophrenia spectrum individuals (FESz). In the discovery sample, T1w scans were acquired from 31 FESz and 31 matched healthy controls (HC). Thickness was calculated for 360 regions in Freesurfer. In the replication sample, high-resolution T1w, T2w, and BOLD-rest scans were acquired from 23 FESz and 32 HC and processed with HCP protocols. Thickness was calculated for regions significant in the discovery sample. After FDR correction (q < .05), left and right parahippocampal area 3 (PHA3) were significantly thinner in FESz. In the replication sample, bilateral PHA3 were again thinner in FESz (q < .05). Exploratory correlation analyses revealed left PHA3 was positively associated with hallucinations and right PHA3 was positively associated with processing speed, working memory, and verbal learning. The novel use of the HCP-MMP in two independent FESz samples revealed thinner bilateral PHA3, suggesting this byway between cortical and limbic processing is a critical site of pathology near the emergence of psychosis., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

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., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

In retrieval of typical episodic memories, recollection leads to retrieval of context details whereas familiarity is only diagnostic for item memory. Unitization is an encoding strategy that allows context details to be processed as item features and therefore increases the involvement of familiarity-based recognition in retrieval of these context details. Relational encoding is a hippocampally-dependent process that stores items and contexts independently. Our previous study Tu and Diana [1] concluded that mixing unitized and non-unitized context details in the same episode reduced the contribution of familiarity to retrieval of any one detail. In the current study, we modified the paradigm by removing visual cues to the context details and the condition-specific blocking during test. Surprisingly, the behavioral data diverged from our 2016 study and indicated that the two manipulated context details in the modified paradigm were processed independently of one another. Neuroimaging data further revealed anterior hippocampal activation was associated with unitization of source information as compared to relational encoding. We also found the predicted increase in bilateral perirhinal cortex activation and decrease in parahippocampal cortex activation during retrieval of unitized color information when compared to relationally-encoded color information. We did not find that same predicted pattern of differences due to unitization of size information., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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.

The current study aimed to identify alterations in brain activation and connectivity related to memory suppression in posttraumatic stress disorder (PTSD) using the Think/No-Think paradigm during functional magnetic resonance imaging (fMRI). Reduced activation in the parahippocampal cortex during No-Think vs. Baseline trials was found in participants with PTSD compared to controls with no history of trauma (pFWE<0.05). Trauma-related intrusive memories (r = 0.562, p = 0.046) and avoidance behaviors (r = 0.636, p = 0.020) were positively correlated with parahippocampal cortex activation during memory suppression in the PTSD group. Psychophysiological interactions (PPI) analysis identified increased functional connectivity between the inferior frontal gyrus and the parahippocampus during memory suppression in the PTSD group compared to trauma-free controls (pFWE<0.05). Our findings support a network-based phenotype for altered memory suppression in individuals with PTSD rooted in dysfunctional parahippocampal-prefrontal coupling. These data validate neural models of PTSD and offer a novel neural circuit for brain-based interventions targeting trauma-related memory., Competing Interests: Conflict of Interest The authors have no conflicts of interest to disclose., (Copyright © 2020. Published by Elsevier B.V.)

A major focus of Alzheimer's disease (AD) research has been finding sensitive outcome measures to disease progression in preclinical AD, as intervention studies begin to target this population. We hypothesize that tailored measures of longitudinal change of the medial temporal lobe (MTL) subregions (the sites of earliest cortical tangle pathology) are more sensitive to disease progression in preclinical AD compared to standard cognitive and plasma NfL measures. Longitudinal T1-weighted MRI of 337 participants were included, divided into amyloid-β negative (Aβ-) controls, cerebral spinal fluid p-tau positive (T+) and negative (T-) preclinical AD (Aβ+ controls), and early prodromal AD. Anterior/posterior hippocampus, entorhinal cortex, Brodmann areas (BA) 35 and 36, and parahippocampal cortex were segmented in baseline MRI using a novel pipeline. Unbiased change rates of subregions were estimated using MRI scans within a 2-year-follow-up period. Experimental results showed that longitudinal atrophy rates of all MTL subregions were significantly higher for T+ preclinical AD and early prodromal AD than controls, but not for T- preclinical AD. Posterior hippocampus and BA35 demonstrated the largest group differences among hippocampus and MTL cortex respectively. None of the cross-sectional MTL measures, longitudinal cognitive measures (PACC, ADAS-Cog) and cross-sectional or longitudinal plasma NfL reached significance in preclinical AD. In conclusion, longitudinal atrophy measurements reflect active neurodegeneration and thus are more directly linked to active disease progression than cross-sectional measurements. Moreover, accelerated atrophy in preclinical AD seems to occur only in the presence of concomitant tau pathology. The proposed longitudinal measurements may serve as efficient outcome measures in clinical trials., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Objective: Medial temporal lobe epilepsy (TLE) is the most common form of medication-resistant focal epilepsy in adults. Despite removal of medial temporal structures, more than one-third of patients continue to have disabling seizures postoperatively. Seizure refractoriness implies that extramedial regions are capable of influencing the brain network and generating seizures. We tested whether abnormalities of structural network integration could be associated with surgical outcomes., Methods: Presurgical magnetic resonance images from 121 patients with drug-resistant TLE across 3 independent epilepsy centers were used to train feed-forward neural network models based on tissue volume or graph-theory measures from whole-brain diffusion tensor imaging structural connectomes. An independent dataset of 47 patients with TLE from 3 other epilepsy centers was used to assess the predictive values of each model and regional anatomical contributions toward surgical treatment results., Results: The receiver operating characteristic area under the curve based on regional betweenness centrality was 0.88, significantly higher than a random model or models based on gray matter volumes, degree, strength, and clustering coefficient. Nodes most strongly contributing to the predictive models involved the bilateral parahippocampal gyri, as well as the superior temporal gyri., Interpretation: Network integration in the medial and lateral temporal regions was related to surgical outcomes. Patients with abnormally integrated structural network nodes were less likely to achieve seizure freedom. These findings are in line with previous observations related to network abnormalities in TLE and expand on the notion of underlying aberrant plasticity. Our findings provide additional information on the mechanisms of surgical refractoriness. ANN NEUROL 2020;88:970-983., (© 2020 American Neurological Association.)

Objective: To test the hypothesis that in periventricular nodular heterotopia (PVNH) structure and function of cortical areas overlying the heterotopic gray matter are preferentially affected., Methods: We studied a group of 40 patients with PVNH and normal-appearing cortex and compared their quantitative MRI markers of brain development, structure, and function to those of 43 age- and sex-matched healthy controls. Inspired by models of neocortical development suggesting that neuronal migration follows a curvilinear path to preserve topologic correspondence between the outer ventricular zone and the cortical surface, we computationally defined the overlying cortex using the Laplace equation and generated synthetic streamlines that link the ventricles, where nodules are located, and the neocortex., Results: We found multilobar cortical thickening encompassing prefrontal, latero-basal temporal, and temporoparietal cortices largely corresponding with the PVNH group-averaged map of the overlying cortex, the latter colocalized with areas of abnormal function, as defined by resting-state fMRI. Patients also presented hippocampal functional hyperconnectivity and malrotation, the latter positively correlating with neocortical maldevelopment indexed by increased folding complexity of the parahippocampus. In clusters of thickness and curvature findings, there were no significant differences between unilateral and bilateral PVNH; contrasting brain-wide metrics between cohorts was also unrevealing. There was no relationship between imaging markers and disease duration except for positive correlation with functional anomalies., Conclusion: Our quantitative image analysis demonstrates widespread structural and functional alterations in PVNH with differential interaction with the overlying cortex and the hippocampus. Right hemispheric predominance may be explained by an early insult, likely genetically determined, on brain morphogenesis., (© 2020 American Academy of Neurology.)

This research investigated whether the medial orbitofrontal cortex (OFC), which is known to code the value of various rewards, is involved in the relationship value recalibration process. Previous research suggests that people upregulate the relationship value of a specific friend in response to the friend's commitment signals. In a functional magnetic resonance imaging study (Study 1), participants imagined receiving high-cost commitment signals, low-cost commitment signals, or no signals from a particular friend. Participants' subjective rating of the relationship value upregulation was positively correlated with medial OFC activity. Subtraction analyses showed that high-cost commitment signals engaged the medial OFC more than did signal failures. An auxiliary analysis revealed that medial OFC activity in response to low-cost commitment signals was negatively correlated with loneliness. To follow-up these findings, we conducted an online vignette study (Study 2), in which participants rated the relationship value of a real friend before and after imagining receiving a series of low-cost commitment signals from that friend. Corroborating the upregulation hypothesis, perceived relationship value significantly increased after imagining a series of commitment signals. This effect was weaker among individuals high in loneliness.

Diagnosis of Alzheimer's disease (AD) is often difficult because of distinct and subjective clinical features, especially in the early stage. FOXO3a protein present in the cognitive centre of brain in inferior temporal region and parahippocampus. FOXO3a can be a potential novel target against AD. AD, Mild Cognitive impairment (MCI) and Geriatric Control (GC) were recruited after diagnosis by clinical assessment, MRI, TauPET and FDG-PET. We have quantified serum FOXO3a by surface plasmon resonance (SPR) and compare with TauPET between of AD, MCI patients and GC. Serum FOXO3A was significantly lower in AD (1.42 ± 0.09 ng/μl) compare to MCI (1.61 ± 0.14 ng/μl) and GC (1.89 ± 0.07 ng/μl). However, the Tau was higher in AD both in serum and also in PET scan. Serum pTau was significantly over-expressed in AD (0.176 ± 0.03 ng/μl), compare to other groups; MCI (0.16 ± 0.014 ng/μl) and GC (0.15 ± 0.024 ng/μl). Serum FOXO3A could significantly differentiate AD vs MCI, MCI vs GC and AD vs GC. However, Tau protein could only differentiate AD vs GC but not MCI vs GC. Serum FOXO3A may serve as novel blood marker for early detection for AD and target for therapeutic intervention., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Preterm-birth increases the risk of several physical, cognitive, neuromotor, and psychosocial problems in children, and is also related to difficulties in the parent-child relationship. Research suggests that the development of early parent-child interactions in general is affected by deviations from typical infant facial characteristics, which may also be important in the case of small, preterm born infants. Therefore, we examined mothers' (N = 22, of whom 17 had no direct experience with preterm birth) neural responses to pictures of preterm and full-term infants using functional magnetic resonance imaging (fMRI). We also explored whether neural responses to preterm and full-term infants correlated with mothers' self-reported tendencies to be nurturing and protective with children, and with mothers' ratings of affection or aversion toward pictures of preterm infants. Results revealed that, compared to pictures of full-term infants, those of preterm infants elicited more activity in specific areas of the brain (dmPFC, right insula, left caudate, hippocampi, parahippocampi, and PAG), that have previously been associated with processing of negative emotions and with empathy. In addition, less activity was seen in one area of the brain (vmPFC) known to be associated with reward-motivation or mental state understanding and perspective-taking. Higher self-reported maternal nurturance was associated with increased activity to pictures of preterm infants vs full-term infants in the caudate, which might reflect approach- or reward-related processing. To conclude, neural responses to preterm infants are related to reward-motivation, mentalizing, negative emotions, and empathy. Future studies should examine whether such neural processing of preterm infant stimuli might underlie difficulties in the parent-child relationship of parents with a preterm child., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Childhood trauma is reliably associated with smaller hippocampal volume in adults; however, this finding has not been shown in children, and even less is known about how sex and trauma interact to affect limbic structural development in children., Methods: Typically developing children aged 9 to 15 years who completed a trauma history questionnaire and structural T1-weighted MRI were included in this study (n = 172; 85 female, 87 male). All children who reported 4 or more traumas (n = 36) composed the high trauma group, and all children who reported 3 or fewer traumas (n = 136) composed the low trauma group. Using multivariate analysis of covariance, we compared FreeSurfer-derived structural MRI volumes (normalized by total intracranial volume) of the amygdalar, hippocampal and parahippocampal regions by sex and trauma level, controlling for age and study site., Results: We found a significant sex × trauma interaction, such that girls with high trauma had greater volumes than boys with high trauma. Follow-up analyses indicated significantly increased volumes for girls and generally decreased volumes for boys, specifically in the hippocampal and parahippocampalregions for the high trauma group; we observed no sex differences in the low trauma group. We noted no interaction effect for the amygdalae., Limitations: We assessed a community sample and did not include a clinical sample. We did not collect data about the ages at which children experienced trauma., Conclusion: Results revealed that psychological trauma affects brain development differently in girls and boys. These findings need to be followed longitudinally to elucidate how structural differences progress and contribute to well-known sex disparities in psychopathology., Competing Interests: None declared., (© 2020 Joule Inc. or its licensors)

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.

The neural basis of memory is highly distributed, but the thalamus is known to play a particularly critical role. However, exactly how the different thalamic nuclei contribute to different kinds of memory is unclear. Moreover, whether thalamic connectivity with the medial temporal lobe (MTL), arguably the most fundamental memory structure, is critical for memory remains unknown. We explore these questions using an fMRI recognition memory paradigm that taps familiarity and recollection (i.e., the two types of memory that support recognition) for objects, faces, and scenes. We show that the mediodorsal thalamus (MDt) plays a material-general role in familiarity, while the anterior thalamus plays a material-general role in recollection. Material-specific regions were found for scene familiarity (ventral posteromedial and pulvinar thalamic nuclei) and face familiarity (left ventrolateral thalamus). Critically, increased functional connectivity between the MDt and the parahippocampal (PHC) and perirhinal cortices (PRC) of the MTL underpinned increases in reported familiarity confidence. These findings suggest that familiarity signals are generated through the dynamic interaction of functionally connected MTL-thalamic structures., (© The Author(s) 2020. Published by Oxford University Press.)

In the last few years the involvement of the medial prefrontal cortex (mPFC) in memory processing has received increased attention. It has been shown to be centrally involved when we use prior knowledge (schemas) to improve learning of related material. With the mPFC also being one of the core hubs of the default mode network (DMN) and the DMN's role in memory retrieval, we decided to investigate whether the mPFC in a schema paradigm acts independent of the DMN. We tested this with data from a cross-sectional developmental study with a schema paradigm. During retrieval of schema items, the mPFC decoupled from the DMN with the degree of decoupling predicting memory performance. This finding suggests that a demand specific reconfiguration of the DMN supports schema memory. Additionally, we found that in the control condition, which relied on episodic memory, activity in the parahippocampal gyrus was positively related to memory performance. We interpret these results as a demand specific network reconfiguration of the DMN: a decoupling of the mPFC to support schema memory and a decoupling of the parahippocampal gyrus facilitating episodic memory., (Copyright © 2020. Published by Elsevier Inc.)

Introduction: Triggering receptor expressed on myeloid cells-like transcript 2 gene (TREML2) is a newly identified AD susceptibility gene. Its missense variant rs3747742-C substantially decreases AD risk in both Caucasians and Han Chinese, but the underlying mechanisms remain elusive. In the present study, to uncover the possible mechanisms by which TREML2 rs3747742-C reduces AD risk, we investigated the possible relation of this variant with AD-related brain structures using a cognitively normal elderly population from Alzheimer's Disease Neuroimaging Initiative (ADNI) database., Methods: In total, 158 cognitively normal elders from ADNI database with complete data for brain structures and TREML2 rs3747742 genotype were included in this study. The association of TREML2 rs3747742 genotype with the structures of three cerebral cortices (entorhinal cortex, middle temporal gyrus, and parahippocampal gyrus), two subcortical regions (amygdala and hippocampus), and three subfields of hippocampus (CA1, CA2 + CA3, and CA4 + dentate gyrus) was investigated., Results: A significant difference was noted in the volume of right CA1 subfield among three genotypes of TREML2 rs3747742 (p = .0364). In the multivariate analysis, TREML2 rs3747742-C significantly increased right CA1 subfield volume after adjusting for age, gender, education years, APOE ε4 status, and intracranial volume under the recessive genetic model (Bonferroni corrected p = .003586)., Conclusion: The present study provides the first evidence that TREML2 rs3747742-C carriers have larger volumes of hippocampal CA1 subfield in a cognitively normal elderly population. These findings imply that enhancement of brain reserve may contribute to the protection of TREML2 rs3747742-C in AD susceptibility., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Background: Patients with a lesion within the amygdala and uncus may develop temporal lobe epilepsy despite having functional mesial structures. Resection of functional hippocampus and surrounding structures may lead to unacceptable iatrogenic deficits. To our knowledge, there is limited descriptions of surgical techniques for selectively resecting the amygdala and uncus lesions while preserving the hippocampus in patients with language-dominant temporal lobe pathology., Methods: Thirteen patients with language-dominant temporal lobe epilepsy related to amygdala-centric lesions were identified. Patients with sclerosis of the mesial structures or evidence of pathology outside of the amygdala-uncus region were excluded. Neuropsychological evaluation confirmed normal function of the mesial structures ipsilateral to the lesion. All patients were worked up with video-EEG, high-resolution brain MRI, neuro-psychology evaluation, and either Wada or functional MRI testing., Results: All patients underwent selective resection of the lesion including amygdala and uncus with preservation of the hippocampus via a transcortical inferior temporal gyrus approach to the mesial temporal lobe. Pathology was compatible with glioneuronal tumors. Post-operative MRI demonstrated complete resection in all patients. Eight of the thirteen patients underwent post-operative neuropsychology evaluations and did not demonstrate any significant decline in tasks of delayed verbal recall or visual memory based on the Rey Auditory Verbal Learning Test (RAVLT). One patient showed a slight decrease in confrontation naming using the Boston Naming Test (BNT). Seizure freedom (Engel class I) was achieved in 12 of 13 patients., Conclusion: Selective transcortical amygdala and uncus resection with hippocampus preservation may be a reasonable way to achieve seizure control while sparing functional mesial structures.

Natural scenes are inherently structured, with meaningful objects appearing in predictable locations. Human vision is tuned to this structure: When scene structure is purposefully jumbled, perception is strongly impaired. Here, we tested how such perceptual effects are reflected in neural sensitivity to scene structure. During separate fMRI and EEG experiments, participants passively viewed scenes whose spatial structure (i.e., the position of scene parts) and categorical structure (i.e., the content of scene parts) could be intact or jumbled. Using multivariate decoding, we show that spatial (but not categorical) scene structure profoundly impacts on cortical processing: Scene-selective responses in occipital and parahippocampal cortices (fMRI) and after 255 ms (EEG) accurately differentiated between spatially intact and jumbled scenes. Importantly, this differentiation was more pronounced for upright than for inverted scenes, indicating genuine sensitivity to spatial structure rather than sensitivity to low-level attributes. Our findings suggest that visual scene analysis is tightly linked to the spatial structure of our natural environments. This link between cortical processing and scene structure may be crucial for rapidly parsing naturalistic visual inputs., (© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

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.

Although higher precuneus activation has often been observed in subjects with addictions when facing addiction-relevant cues, the recruitment of the precuneus is not consistent across studies. Here, we examined the extent to which addiction severity may relate to precuneus involvement during cue reactivity in internet gaming disorder (IGD). We recruited 65 subjects with IGD, collected brain responses when exposed to gaming cues and assessed brain structure. We correlated IGD severity with brain responses during a cue-craving task, precuneus volume, and connectivity with respect to inputs/outputs to/from the precuneus. In the cue-craving task, IGD severity was positively correlated with precuneus activation when exposed to gaming cues. IGD severity was also positively correlated with the volume of precuneus and connectivity from the hippocampal gyrus to the precuneus. IGD severity was also negatively correlated with connectivity from the middle frontal gyrus to the precuneus. In IGD, IGD severity relates to precuneus involvement with respect to functionality, morphology, and connectivity. The precuneus may act as a platform for integrating potential contradictory information between executive control and sub-cortical cravings., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

In his seminal works, Endel Tulving argued that functionally distinct memory systems give rise to subjective experiences of remembering and knowing (i.e., recollection- vs. familiarity-based memory, respectively). Evidence shows that emotion specifically enhances recollection, and this effect is subserved by a synergistic mechanism involving the amygdala (AMY) and hippocampus (HC). In extreme circumstances, however, uncontrolled recollection of highly distressing memories may lead to symptoms of affective disorders. Therefore, it is important to understand the factors that can diminish such detrimental effects. Here, we investigated the effects of Focused Attention (FA) on emotional recollection. FA is an emotion regulation strategy that has been proven quite effective in reducing the impact of emotional responses associated with the recollection of distressing autobiographical memories, but its impact during emotional memory encoding is not known. Functional MRI and eye-tracking data were recorded while participants viewed a series of composite negative and neutral images with distinguishable foreground (FG) and background (BG) areas. Participants were instructed to focus either on the FG or BG content of the images and to rate their emotional responses. About 4 days later, participants' memory was assessed using the R/K procedure, to indicate whether they Recollected specific contextual details about the encoded images or the images were just familiar to them - i.e., participants only Knew that they saw the pictures without being able to remember specific contextual details. First, results revealed that FA was successful in decreasing memory for emotional pictures viewed in BG Focus condition, and this effect was driven by recollection-based retrieval. Second, the BG Focus condition was associated with decreased activity in the AMY, HC, and anterior parahippocampal gyrus for subsequently recollected emotional items. Moreover, correlation analyses also showed that reduced activity in these regions predicted greater reduction in emotional recollection following FA. These results demonstrate the effectiveness of FA in mitigating emotional experiences and emotional recollection associated with unpleasant emotional events., (Copyright © 2020 Elsevier Ltd. All rights reserved.)