An investigation into the abnormal dynamic connection mechanism of generalized anxiety disorders based on non-homogeneous Markov models.

BACKGROUND: The dynamic and hierarchical nature of the functional brain network. The neural dynamical systems tend to converge to multiple attractors (stable fixed points or dynamical states) in long run. Little is known about how the changes in this brain dynamic "long-term" behavior of the connectivity flow of brain network in generalized anxiety disorder (GAD). METHODS: This study recruited 92 patients with GAD and 77 healthy controls (HC). We applied a reachable probability approach combining a Non-homogeneous Markov model with transition probability to quantify all possible connectivity flows and the hierarchical structure of brain functional systems at the dynamic level and the stationary probability vector (10-step transition probabilities) to describe the steady state of the system in the long run. A random forest algorithm was conducted to predict the severity of anxiety. RESULTS: The dynamic functional patterns in distributed brain networks had larger possibility to converge in bilateral thalamus, posterior cingulate cortex (PCC), right superior occipital gyrus (SOG) and smaller possibility to converge in bilateral superior temporal gyrus (STG) and right parahippocampal gyrus (PHG) in patients with GAD compared to HC. The abnormal transition probability pattern could predict anxiety severity in patients with GAD. LIMITATIONS: Small samples and subjects taking medications may have influenced our results. Future studies are expected to rule out the potential confounding effects. CONCLUSION: Our results have revealed abnormal dynamic neural communication and integration in emotion regulation in patients with GAD, which give new insights to understand the dynamics of brain function of patients with GAD.

Increased neural activity of right temporo-parietal junction causes different effect on altruism in situations of advantageous and disadvantageous inequity.

Altruism is defined as the performance of "costly acts that confer economic benefits on other individuals", which is one of the major puzzles in the behavioural sciences today. Altruistic behaviour not only facilitates interpersonal adaptation and harmony but also enhances social welfare and social responsibility. The right temporo-parietal junction (rTPJ) has been proposed as playing a key role in guiding human altruistic behaviour, but its precise functional contribution to altruistic behaviour in situations of advantageous and disadvantageous inequity remains unclear. The purpose of this study was to modulate the activation of the rTPJ through transcranial direct current stimulation (tDCS) in order to clarify the causal role of the rTPJ in altruistic behaviour in situations of advantageous and disadvantageous inequity. A total of 106 participants were randomly assigned to one of three stimulation conditions: anodal tDCS stimulation on the rTPJ; sham tDCS stimulation on the rTPJ and anodal tDCS stimulation on the primary visual cortex (VC)as the control group, and. After 20 min of stimulation, participants undertook a modified dictator game that measured altruistic behaviour. Mixed-effect logistic regressions were applied to statistical analyses in this study. The results indicated that anodal tDCS over the rTPJ increased participants' altruistic tendency by increasing their tendency to choose altruistic options in trials with higher cost, as well as their tendency to behave altruistically in situations of advantageous but not disadvantageous inequity. These results suggested that increased neural activity of the rTPJ leads to different impacts on altruism in these two different inequity situations.

Mentalizing in an economic games context is associated with enhanced activation and connectivity in the left temporoparietal junction.

Prior studies in Social Neuroeconomics have consistently reported activation in social cognition regions during interactive economic games, suggesting mentalizing during economic choice. Such mentalizing occurs during active participation in the game, as well as during passive observation of others' interactions. We designed a novel version of the classic false-belief task (FBT) in which participants read vignettes about interactions between agents in the ultimatum and trust games and were subsequently asked to infer the agents' beliefs. We compared activation patterns during the economic games FBT to those during the classic FBT using conjunction analyses. We find significant overlap in the left temporoparietal junction (TPJ) and dorsal medial prefrontal cortex, as well as the temporal pole (TP) during two task phases: belief formation and belief inference. Moreover, generalized Psychophysiological Interaction (gPPI) analyses show that during belief formation, the right TPJ is a target of both the left TPJ and the right TP seed regions, whereas during belief inferences all seed regions show interconnectivity with each other. These results indicate that across different task types and phases, mentalizing is associated with activation and connectivity across central nodes of the social cognition network. Importantly, this is the case for both the novel economic games and the classic FBTs.

Parametric Cognitive Load Reveals Hidden Costs in the Neural Processing of Perfectly Intelligible Degraded Speech.

Speech is often degraded by environmental noise or hearing impairment. People can compensate for degradation, but this requires cognitive effort. Previous research has identified frontotemporal networks involved in effortful perception, but materials in these works were also less intelligible, and so it is not clear whether activity reflected effort or intelligibility differences. We used functional magnetic resonance imaging to assess the degree to which spoken sentences were processed under distraction and whether this depended on speech quality even when intelligibility of degraded speech was matched to that of clear speech (close to 100%). On each trial, male and female human participants either attended to a sentence or to a concurrent multiple object tracking (MOT) task that imposed parametric cognitive load. Activity in bilateral anterior insula reflected task demands; during the MOT task, activity increased as cognitive load increased, and during speech listening, activity increased as speech became more degraded. In marked contrast, activity in bilateral anterior temporal cortex was speech selective and gated by attention when speech was degraded. In this region, performance of the MOT task with a trivial load blocked processing of degraded speech, whereas processing of clear speech was unaffected. As load increased, responses to clear speech in these areas declined, consistent with reduced capacity to process it. This result dissociates cognitive control from speech processing; substantially less cognitive control is required to process clear speech than is required to understand even very mildly degraded, 100% intelligible speech. Perceptual and control systems clearly interact dynamically during real-world speech comprehension.SIGNIFICANCE STATEMENT Speech is often perfectly intelligible even when degraded, for example, by background sound, phone transmission, or hearing loss. How does degradation alter cognitive demands? Here, we use fMRI to demonstrate a novel and critical role for cognitive control in the processing of mildly degraded but perfectly intelligible speech. We compare speech that is matched for intelligibility but differs in putative control demands, dissociating cognitive control from speech processing. We also impose a parametric cognitive load during perception, dissociating processes that depend on tasks from those that depend on available capacity. Our findings distinguish between frontal and temporal contributions to speech perception and reveal a hidden cost to processing mildly degraded speech, underscoring the importance of cognitive control for everyday speech comprehension.

Neurodegeneration and astrogliosis in the entorhinal cortex in Alzheimer's disease: Stereological layer-specific assessment and proteomic analysis.

INTRODUCTION: The entorhinal cortex is among the earliest areas involved in Alzheimer's disease. Volume reduction and neural loss in this area have been widely reported. Human entorhinal cortex atrophy is, in part, due to neural loss, but microglial and/or astroglial involvement in the different layers remains unclear. Additionally, -omic approaches in the human entorhinal cortex are scarce. METHODS: Herein, stereological layer-specific and proteomic analyses were carried out in the human brain. RESULTS: Neurodegeneration, microglial reduction, and astrogliosis have been demonstrated, and proteomic data have revealed relationships with up- (S100A6, PPP1R1B, BAG3, and PRDX6) and downregulated (GSK3B, SYN1, DLG4, and RAB3A) proteins. Namely, clusters of these proteins were related to synaptic, neuroinflammatory, and oxidative stress processes. DISCUSSION: Differential layer involvement among neural and glial populations determined by proteinopathies and identified proteins related to neurodegeneration and astrogliosis could explain how the cortical circuitry facilitates pathological spreading within the medial temporal lobe.

Inter-modality assessment of medial temporal lobe atrophy in a non-demented population: application of a visual rating scale template across radiologists with varying clinical experience.

OBJECTIVES: To assess inter-modality agreement and accuracy for medial temporal lobe atrophy (MTA) ratings across radiologists with varying clinical experience in a non-demented population. METHODS: Four raters (two junior radiologists and two senior neuroradiologists) rated MTA on CT and MRI scans using Scheltens' MTA scale. Ratings were compared to a consensus rating by two experienced neuroradiologists for estimation of true positive and negative rates (TPR and TNR) and over- and underestimation of MTA. Inter-modality agreement expressed as Cohen's κ (dichotomized data), Cohen's κw, and two-way mixed, single measures, consistency ICC (ordinal data) were determined. Adequate agreement was defined as κ/κw ≥ 0.80 and ICC ≥ 0.80 (significance level at 95% CI ≥ 0.65). RESULTS: Forty-nine subjects (median age 72 years, 27% abnormal MTA) with cognitive impairment were included. Only junior radiologists achieved adequate agreement expressed as Cohen's κ. All raters achieved adequate agreement expressed as Cohen's κw and ICC. True positive rates varied from 69 to 100% and TNR varied from 85 to 100%. No under- or overestimation of MTA was observed. Ratings did not differ between radiologists. CONCLUSION: We conclude that radiologists with varying experience achieve adequate inter-modality agreement and similar accuracy when Scheltens' MTA scale is used to rate MTA on a non-demented population. However, TPR varied between radiologists which could be attributed to rating style differences. KEY POINTS: • Radiologists with varying experience achieve adequate inter-modality agreement with similar accuracy when Scheltens' MTA scale is used to rate MTA on a non-demented population. • Differences in rating styles might affect accuracy, this was most evident for senior neuroradiologists, and only junior radiologists achieved adequate agreement on dichotomized (abnormal/normal) ratings. • The use of an MTA scale template might compensate for varying clinical experience which could make it applicable for clinical use.

Self-awareness for financial decision making abilities is linked to right temporal cortical thickness in older adults.

Everyday financial decision making and the awareness of the integrity of one's financial decision making abilities (or financial awareness) are both critical to study in older adults as they can help identify those at risk for making suboptimal financial decisions and prevent financial loss. In the current study, we examined the cognitive and cortical thickness correlates of financial decision making and financial awareness in 59 community-dwelling participants co-enrolled in a larger study (mean age=68.35 years (SD=5.5), mean education=15.91 (SD=2.36), 61% = women, 67% = White, 30% = Black participants). Data from standardized measures of financial decision making and cognition was investigated along with FreeSurfer (v. 5.3) derived thickness regions. Based on metacognitive frameworks, financial awareness was measured along with a well-validated measure of memory awareness. Results revealed that numeracy, executive functioning and vocabulary were associated with financial decision making, whereas in analysis adjusted for financial decision making, memory awareness relative to cognition was most strongly linked to financial awareness. No significant associations between thickness and financial decision making were found. However, both financial and memory awareness were associated with the same right-hemisphere temporal thickness regions underscoring the idea of a common substrate of awareness. Interestingly, our findings converge with the emerging work on financial exploitation in which the right sided temporal regions have been found to play a prominent role. Incorporating the contributing role of self-awareness in various models of financial exploitation will be an important consideration for future studies.

Functional Specialization of the Medial Temporal Lobes in Human Recognition Memory: Dissociating Effects of Hippocampal versus Parahippocampal Damage.

A central debate in the systems neuroscience of memory concerns whether different medial temporal lobe (MTL) structures support different processes in recognition memory. Using two recognition memory paradigms, we tested a rare patient (MH) with a perirhinal lesion that appeared to spare the hippocampus. Consistent with a similar previous case, MH showed impaired familiarity and preserved recollection. When compared with patients with hippocampal lesions appearing to spare perirhinal cortex, MH showed greater impairment on familiarity and less on recollection. Nevertheless, the hippocampal patients also showed impaired familiarity compared with healthy controls. However, when replacing this traditional categorization of patients with analyses relating memory performance to continuous measures of damage across patients, hippocampal volume uniquely predicted recollection, whereas parahippocampal, rather than perirhinal, volume uniquely predicted familiarity. We consider whether the familiarity impairment in MH and our patients with hippocampal lesions arises from "subthreshold" damage to parahippocampal cortex (PHC). Our data provide the most compelling neuropsychological support yet for dual-process models of recognition memory, whereby recollection and familiarity depend on different MTL structures, and may support a role for PHC in familiarity. Our study highlights the value of supplementing single-case studies with examinations of continuous brain-behavior relationships across larger patient groups.

Effects of Thai Local Ingredient Odorants, Litsea cubeba and Garlic Essential Oils, on Brainwaves and Moods.

The functional food market is growing with a compound annual growth rate of 7.9%. Thai food recipes use several kinds of herbs. Lemongrass, garlic, and turmeric are ingredients used in Thai curry paste. Essential oils released in the preparation step create the flavor and fragrance of the famous tom yum and massaman dishes. While the biological activities of these ingredients have been investigated, including the antioxidant, anti-inflammatory, and antimicrobial activities, there is still a lack of understanding regarding the responses to the essential oils of these plants. To investigate the effects of essential oil inhalation on the brain and mood responses, electroencephalography was carried out during the non-task resting state, and self-assessment of the mood state was performed. The essential oils were prepared in several dilutions in the range of the supra-threshold level. The results show that Litsea cubeba oil inhalation showed a sedative effect, observed from alpha and beta wave power reductions. The frontal and temporal regions of the brain were involved in the wave alterations. Garlic oil increased the alpha wave power at lower concentrations; however, a sedative effect was also observed at higher concentrations. Lower dilution oil induced changes in the fast alpha activity in the frontal region. The alpha and beta wave powers were decreased with higher dilution oils, particularly in the temporal, parietal, and occipital regions. Both Litsea cubeba and turmeric oils resulted in better positive moods than garlic oil. Garlic oil caused more negative moods than the others. The psychophysiological activities and the related brain functions require further investigation. The knowledge obtained from this study may be used to design functional food products.

Structural brain assessment of temporal lobe epilepsy based on voxel-based and surface-based morphological features.

AIM OF THE STUDY: This study aimed to assess the cerebral voxel-based and surface-based morphological abnormalities of patients with temporal lobe epilepsy (TLE). MATERIALS AND METHODS: A total of 100 healthy adults and 73 patients with TLE were enrolled in this study, and their 3D T1-weighted MRI data were collected. Voxel-based morphology (VBM) and surface-based morphology (SBM) tools were used to compare the morphological differences between healthy adults and patients with TLE. Receiver-operating characteristic (ROC) curves were used to acquire the boundary values for detecting morphological abnormalities in regions of interest from the corrected VBM and SBM analysis. RESULTS: Our results showed that cortical voxels and decreased thickness areas were located in the widespread cortex and subcortical structures in the TLE group. However, after completing the analysis, we found that the left-TLE lesions were limited to the left temporal pole and left hippocampus, while the right-TLE lesions were located in the bilateral medial temporal lobe, including the right hippocampus and bilateral amygdala. ROC-curve results showed that the volume of the left hippocampus at 4,124.45 mm3 and the thickness of the left temporal pole cortex at 3.50 mm could be used as optimal boundary values based on the curves of the left-TLE group. The right-TLE group curves were poor. CONCLUSIONS: Widespread cerebral morphological TLE abnormalities were represented in this study. However, the lesions may be limited after completing a corrected comparison with clinical information. Boundary values of left-TLE group lesions were also obtained.

Modulating the activity of right temporo-parietal junction increases bidding behavior in lottery contests.

Contest often involves bids that are higher than the Nash equilibrium, and overbidding behaviour closely relates to personal reasoning and judgement. The right temporo-parietal junction (rTPJ) plays an important role in social, cognitive and inference decision-making. In the present study, we investigated the effect of transcranial direct current stimulation (tDCS) of the rTPJ on overbidding behaviour by using a modified model-lottery contests task. Our results showed that participants that received cathodal-stimulation had significantly higher expenditure compared to participants that received anodal and sham stimulation. Cathodal-stimulation may reduce the participants' ability to infer other contestants' intention or may modulate the non-monetary utility of winning. Our data indicate that excitability of the rTPJ may contribute to overbidding behaviour.

The Neural Signature of Social Dominance Discrimination by Means of Fast Periodic Visual Stimulation.

Hierarchy is a pervasive feature of social organization. The ability to rapidly discriminate hierarchical information is critical for social interaction. Here, we took advantage of a special technique in electroencephalography (EEG) known as fast periodic visual stimulation (FPVS). We used this technique, which captures the automatic perception of faces, to explore the neural signature of social dominance discrimination. A stream of computer-generated faces was presented at 6 Hz, i.e. six faces/second. In the experimental condition, faces alternated from high to low social dominance within a sequence, bringing about a frequency of interest of 3 Hz (6 Hz/2), i.e. three high/low dominance faces appeared in one second. In two control conditions, we presented faces which came exclusively from one of two hierarchical ranks (either lower or higher). Participants were asked to respond to information unrelated to this hierarchical information, namely pressing the spacebar when the fixation changes color. Results revealed a significant 3 Hz response for the experimental condition only. This response was located bilaterally in the occipito-temporal region, indicating discrimination of differences in social dominance. Through the use of FPVS, we provide electrophysiological evidence to show that social hierarchical information can be detected automatically.

Medial temporal atrophy in preclinical dementia: Visual and automated assessment during six year follow-up.

Medial temporal lobe (MTL) atrophy is an important morphological marker of many dementias and is closely related to cognitive decline. In this study we aimed to characterize longitudinal progression of MTL atrophy in 93 individuals with subjective cognitive decline and mild cognitive impairment followed up over six years, and to assess if clinical rating scales are able to detect these changes. All MRI images were visually rated according to Scheltens' scale of medial temporal atrophy (MTA) by two neuroradiologists and AVRA, a software for automated MTA ratings. The images were also segmented using FreeSurfer's longitudinal pipeline in order to compare the MTA ratings to volumes of the hippocampi and inferior lateral ventricles. We found that MTL atrophy rates increased with CSF biomarker abnormality, used to define preclinical stages of Alzheimer's Disease. Both AVRA's and the radiologists' MTA ratings showed similar longitudinal trends as the subcortical volumes, suggesting that visual rating scales provide a valid alternative to automatic segmentations. Our results further showed that it took more than 8 years on average for individuals with mild cognitive impairment, and an Alzheimer's disease biomarker profile, to increase the MTA score by one. This suggests that discrete MTA ratings are too coarse for tracking individual MTL atrophy in short time spans. While the MTA scores from each radiologist showed strong correlations to subcortical volumes, the inter-rater agreement was low. We conclude that the main limitation of quantifying MTL atrophy with visual ratings in clinics is the subjectiveness of the assessment.

Transcriptomic evidence that von Economo neurons are regionally specialized extratelencephalic-projecting excitatory neurons.

von Economo neurons (VENs) are bipolar, spindle-shaped neurons restricted to layer 5 of human frontoinsula and anterior cingulate cortex that appear to be selectively vulnerable to neuropsychiatric and neurodegenerative diseases, although little is known about other VEN cellular phenotypes. Single nucleus RNA-sequencing of frontoinsula layer 5 identifies a transcriptomically-defined cell cluster that contained VENs, but also fork cells and a subset of pyramidal neurons. Cross-species alignment of this cell cluster with a well-annotated mouse classification shows strong homology to extratelencephalic (ET) excitatory neurons that project to subcerebral targets. This cluster also shows strong homology to a putative ET cluster in human temporal cortex, but with a strikingly specific regional signature. Together these results suggest that VENs are a regionally distinctive type of ET neuron. Additionally, we describe the first patch clamp recordings of VENs from neurosurgically-resected tissue that show distinctive intrinsic membrane properties relative to neighboring pyramidal neurons.

Value-based decision-making of cigarette and nondrug rewards in dependent and occasional cigarette smokers: An FMRI study.

Little is known about the neural functioning that underpins drug valuation and choice in addiction, including nicotine dependence. Following ad libitum smoking, 19 dependent smokers (smoked≥10/day) and 19 occasional smokers (smoked 0.5-5/week) completed a decision-making task. First, participants stated how much they were willing-to-pay for various amounts of cigarettes and shop vouchers. Second, during functional magnetic resonance imaging, participants decided if they wanted to buy these cigarettes and vouchers for a set amount of money. We examined decision-making behaviour and brain activity when faced with cigarette and voucher decisions, purchasing (vs not purchasing) cigarettes and vouchers, and "value signals" where brain activity correlated with cigarette and voucher value. Dependent smokers had a higher willingness-to-pay for cigarettes and greater activity in the bilateral middle temporal gyrus when faced with cigarette decisions than occasional smokers. Across both groups, the decision to buy cigarettes was associated with activity in the left paracingulate gyrus, right nucleus accumbens, and left amygdala. The decision to buy vouchers was associated with activity in the left superior frontal gyrus, but dependent smokers showed weaker activity in the left posterior cingulate gyrus than occasional smokers. Across both groups, cigarette value signals were observed in the left striatum and ventromedial prefrontal cortex. To summarise, nicotine dependence was associated with greater behavioural valuation of cigarettes and brain activity during cigarette decisions. When purchasing cigarettes and vouchers, reward and decision-related brain regions were activated in both groups. For the first time, we identified value signals for cigarettes in the brain.

Computational Mechanisms for Perceptual Stability using Disparity and Motion Parallax.

Walking and other forms of self-motion create global motion patterns across our eyes. With the resulting stream of visual signals, how do we perceive ourselves as moving through a stable world? Although the neural mechanisms are largely unknown, human studies (Warren and Rushton, 2009) provide strong evidence that the visual system is capable of parsing the global motion into two components: one due to self-motion and the other due to independently moving objects. In the present study, we use computational modeling to investigate potential neural mechanisms for stabilizing visual perception during self-motion that build on neurophysiology of the middle temporal (MT) and medial superior temporal (MST) areas. One such mechanism leverages direction, speed, and disparity tuning of cells in dorsal MST (MSTd) to estimate the combined motion parallax and disparity signals attributed to the observer's self-motion. Feedback from the most active MSTd cell subpopulations suppresses motion signals in MT that locally match the preference of the MSTd cell in both parallax and disparity. This mechanism combined with local surround inhibition in MT allows the model to estimate self-motion while maintaining a sparse motion representation that is compatible with perceptual stability. A key consequence is that after signals compatible with the observer's self-motion are suppressed, the direction of independently moving objects is represented in a world-relative rather than observer-relative reference frame. Our analysis explicates how temporal dynamics and joint motion parallax-disparity tuning resolve the world-relative motion of moving objects and establish perceptual stability. Together, these mechanisms capture findings on the perception of object motion during self-motion.SIGNIFICANCE STATEMENT The image integrated by our eyes as we move through our environment undergoes constant flux as trees, buildings, and other surroundings stream by us. If our view can change so radically from one moment to the next, how do we perceive a stable world? Although progress has been made in understanding how this works, little is known about the underlying brain mechanisms. We propose a computational solution whereby multiple brain areas communicate to suppress the motion attributed to our movement relative to the stationary world, which is often responsible for a large proportion of the flux across the visual field. We simulated the proposed neural mechanisms and tested model estimates using data from human perceptual studies.

Multimodal assessment of language and memory reorganization: a proof of concept in two patients with drug-resistant temporal lobe epilepsy.

We report two patients suffering from drug-resistant temporal lobe epilepsy to show how their neuroplasticity can be apprehended using a multimodal, integrative and clinically relevant approach. This is a proof of concept based on using multimodal data including: (1) white matter structural connectivity (DTI) of the main tracts involved in language and memory; (2) neurophysiological biomarkers (fMRI-BOLD signal and LI lateralization indices); and (3) cognitive scores as measured during the neuropsychological assessment. We characterized tri-modal data for each patient using a descriptive integrative approach, in terms of reorganization and by comparing with a group of healthy participants. This proof of concept suggests that the inclusion of multimodal data in clinical studies is currently a major challenge. Since the various datasets obtained from MRI neuroimaging and cognitive scores are probably interrelated, it is important to go beyond the mono-modal approach and move towards greater integration of several multimodal data. Multimodal integration of anatomical, functional, and cognitive data facilitates the identification of comprehensive neurocognitive patterns in epileptic patients, thus enabling clinicians to differentiate between reorganization profiles and help to predict post-surgical outcomes for curative neurosurgery.

Anxiety symptoms are associated with smaller insular and orbitofrontal cortex volumes in late-life depression.

BACKGROUND: Increasing understanding of the neural correlates of anxiety symptoms in late-life depression (LLD) could inform the development of more targeted and effective treatments. METHODS: Grey matter volume (GMV) was assessed with volumetric magnetic resonance imaging in a sample of 113 adults ≥60 years with MDD using the following regions of interest: amygdala, anterior cingulate cortex (ACC), insula, orbitofrontal cortex (OFC), and temporal cortex. RESULTS: After controlling for demographic (age, sex, education) and clinical variables (antidepressant use, anxiolytic use, duration of illness, medical comorbidity, cognitive functioning), greater severity of anxiety symptoms was associated with lower GMV bilaterally in the insula, F(1,102) = 6.63, p = 0.01, and OFC, F(1,102) = 8.35, p = 0.005. By contrast, depressive symptom severity was significantly associated with lower bilateral insula volumes, F(1,102) = 6.43, p = 0.01, but not OFC volumes, F(1,102) = 5.37, p = 0.02. LIMITATIONS: Limitations include (1) the relatively mild nature of anxiety symptoms in our sample; (2) the cross-sectional research design, which prohibits inferences of directionality; (3) the relatively homogenous demographic of the sample, and (4) the exclusion of participants with significant psychiatric comorbidity, suicidality, or cognitive impairment. CONCLUSIONS: Decreased OFC volumes may serve as a unique biomarker of anxiety symptoms in LLD. Future longitudinal and clinical studies with long-term follow up and more diverse samples will help further elucidate the biological, psychological, and social factors affecting associations between anxiety and brain morphology in LLD.

Association of Smell Identification Deficit with Alzheimer's Disease Assessment Scale-Cognitive Subscale, Japanese Version Scores and Brain Atrophy in Patients with Dementia.

INTRODUCTION: Olfactory dysfunction is commonly associated with Alzheimer's disease (AD) and may be related to disorder of the central olfactory processing system. In this work, therefore, we examined the relationships between olfactory changes and the most affected cognitive domain or degree of brain atrophy in patients with AD and mild cognitive impairment (MCI). METHODS: The subjects were 55 AD patients and 27 MCI patients. Smell identification tests were performed using Odor Stick Identification Test for Japanese -(OSIT-J). The severity and nature of cognitive dysfunctions were evaluated using the AD Assessment Scale-cognitive subscale, Japanese version (ADAS-Jcog). MRI with voxel-based specific regional analysis system for AD software was used for evaluation of brain atrophy. RESULTS: -OSIT-J scores were significantly correlated with total -ADAS-Jcog scores, as well as with ADAS-Jcog subscale items of word recall task, orientation (memory domain) and ideational praxis. Smell identification deficit was proportional to the degree of atrophy of the medial temporal lobe. CONCLUSION: Smell identification deficit in AD/MCI is strongly associated with the memory domain of cognitive function and with atrophy of the medial temporal lobe.