Medial Temporal Cortex Research Articles

Cognitive dysfunction and brain mechanisms in major depression disorder

The prevalence of major depressed disorder increased rapidly in recent year all over the world and has become a heavy burden of society. So research on depression has become a hot topic. A great amount of studies found that patients with major depression disorder had impaired cognition. Cognitive dysfunction, the important symptom of depression, has been regarded as not only an indicator of illness, but also an obstacle to the elimination of depressive mood and the overall recovery of the disease. Exploring cognitive dysfunction and the potential brain mechanism meant significantly to understanding the etiology of major depression disorder, which could benefit the prevention, diagnosis, treatment of this mental disease. Therefore, the current research aimed to discuss cognitive dysfunction, the potential brain mechanism of the impaired dysfunction as well as the molecular factors behind major depression disorder, try to threw light on the abnormal macro-brain activity and micro-molecular marker of major depression disorder. The literatures showed that patients with major depression disorder had abnormalities in executive function, attention, memory and reaction speed. Deficit in executive function was mainly related to abnormality in prefrontal lobe and the connected subcutaneous nuclei; attention deficits had connection with abnormality in the frontal network connection, occipital lobe and cingulate gyrus; and memory defects are corresponded to abnormality in the hippocampus, cingulate gyrus, and medial temporal cortex. In addition, the abnormal neurotransmitters or brain-derived neuronal factors, and long-term stress state may also be the cause of depressive symptoms and abnormal cognitive levels. At present, the study of brain structure is relatively rough, mainly focusing on the changes in a big brain area, such as the hippocampus, prefrontal cortex, etc. In the future, high-resolution magnetic resonance imaging technology are needed to study more refined brain structures, such as CA1-3, entorhinal cortex to provide biological targets for neuromodulation treatment of various non-pharmacological interventions. Future studies also need to balance as much as possible irrelevant variables such as disease progression, severity of depression, gender, and neuropsychological tests. Besides, the causal link between neuroimaging and molecular biomarkers and depression remains unclear and longitudinal studies should be taken into consideration. As for clinical studies, we suggested to improve the traditional criteria of mental illness classification by combining the biological abnormality found by research evidence. Specifically, future studies of major depression disorder can consider cognitive dysfunctions assessed by psychological cognitive tasks; multimodal brain image and neurophysiological data to construct multidimensional computational modeling, in order to systematically explore potential biomarkers of depression, further identify the subtypes of depression. New classification criteria would provide full understanding of the pathogenesis as well as individual diagnosis and treatment of major depression disorder.

PATTERN OF CORTICAL THINNING AND SHAPE VARIABILITY RELATED TO ALZHEIMER’S DISEASE IN REGIONS AFFECTED BY EARLIEST NEUROFIBRILLARY TANGLE PATHOLOGY

The medial temporal lobe (MTL) is the site of earliest neurofibrillary tangle (NFT, Figure 1A) pathology in Alzheimer's disease (AD). Characterizing the patterns of cortical thinning and shape change in the MTL and relating them to disease progression may be useful for the staging, early detection and monitoring of AD. In addition, we hypothesize that the pattern of AD-related thinning may vary between different anatomical variants of the MTL (Figure 1B), as defined by the folding pattern of the collateral sulcus. We selected T1-weighted MRI scans of 603 subjects from ADNI (Table 1); amyloid negative (A-) controls, A+ controls, A+ early mild cognitive impairment (MCI), A+ late MCI and A+ AD. Bilateral entorhinal cortex (ERC), Brodmann areas (BA) 35 and 36 were segmented automatically. A novel multi-template shape analysis pipeline was applied to extract regional thickness, establish pointwise correspondences and quantify anatomical variability of two major MTL variants. For each MTL variant in each hemisphere, cortical thickness was compared at each point between an A- control and all other groups, yielding a t-statistic map. The effect of AD on MTL cortex shape was evaluated using principal component analysis and support vector machine on the segmentations of the A- control and A+ AD patients (opposite ends of the AD spectrum). The statistical maps in Figure 2 show a consistent pattern of disease progression: initiating in BA35 and progressing to ERC and BA36 in later stages; consistent with the NFT progression staging by Braak and Braak. The first site of cortical thinning seems to be different in variant 1 compared to variant 2; i.e. more lateral in variant 1. Moreover, Figure 3 reveals that AD is associated with decrease in overall size of the MTL, cortical thinning and widening of the CS. T-statistical maps of the contrast between amyloid-negative cognitively normal (CN) adults and the other 4 groups (amyloid-positive CN, EMCI, LMCI and AD) of both variant-templates with age and education as covariates. Left and right hemispheres are analyzed separately. Black contours outline significant clusters after cluster-level family-wise error rate correction. The corrected p-value of each cluster is indicated by the white arrow and text. The corresponding anatomical labels are shown in the first column. The Effect of AD on medial temporal lobe cortex shape of the two anatomical variants. A support vector machine (SVM) is trained to discriminate amyloid-negative cognitively normal adults and amyloid- positive AD cases (cases from the other groups were excluded). The vector orthogonal to the SVM hyperplane, which is assumed to be the direction that best discriminate the two groups, is visualized. Our novel shape analysis revealed the progression of cortical thinning and shape changes of the MTL cortex, the earliest site of NFT pathology. This effect may differ among anatomical variants. Summary thickness measurements extracted from the significant clusters (Figure 2) and the features associated with shape changes may be useful markers for early detection and tracking disease progression.

Abstract B39: A pilot study of neuropsychological functions, APOE, and amyloid imaging in patients with gliomas

Abstract Patients with brain tumors treated with radiotherapy (RT) often develop cognitive dysfunction, and recent studies suggest that the apolipoprotein (APOE) ε-4 allele may influence cognitive outcome. The ε-4 allele promotes beta (β) amyloid deposition in the cortex, and preliminary evidence suggests that RT may be associated with β-amyloid deposition. In this pilot study, we assessed neuropsychological functions and β-amyloid retention using 18F-florbetaben PET in a subset of brain tumor patients who participated in our study of APOE polymorphisms and cognitive functions. Twenty glioma patients treated with conformal RT ± chemotherapy participated in the study: 6 were APOE ε-4 carriers and 14 were non-ε-4 carriers. Patients completed a neuropsychological reevaluation and brain MRI and 18F-florbetaben PET scans. The results of Wilcoxon rank sums test comparisons between prior and current assessments showed a significant decline in selective attention (Brief Test of Attention, p=0.018), and a near-significant decline in verbal learning (Hopkins Verbal Learning Test-Learning, p=0.07). Comparisons between assessments by APOE status showed a significant decline in attention and working memory (WAIS-III digits forward, p=0.028 and digits backward, p=0.032) among APOE ε-4 carriers. Comparisons of PET regional standard uptake value ratios (SUVRs) showed near-significant differences for the medial temporal cortex (p=0.069) and the putamen (p=0.069), with non-ε-4 carriers having higher SUVRs. The findings suggest that glioma patients may experience progressive worsening in attention and executive functions several years after treatment with RT ± chemotherapy, and that the APOE ε-4 allele may moderate cognitive decline. Note: This abstract was not presented at the conference. Citation Format: Denise Correa, Maria Kryza-Lacombe, Xiaosun Zhou, Raymond Baser, Brad Beattie, Zodina Beiene, Irene Orlow, John Humm, Lisa DeAngelis, Wolfgang Weber, Joseph Osborne. A pilot study of neuropsychological functions, APOE, and amyloid imaging in patients with gliomas [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B39.

Meaningful inhibition: Exploring the role of meaning and modality in response inhibition

We frequently guide our decisions about when and how to act based on the meanings of perceptual inputs: we might avoid treading on a flower, but not on a leaf. However, most research on response inhibition has used simple perceptual stimuli devoid of meaning. In two Go/No-Go experiments, we examined whether the neural mechanisms supporting response inhibition are influenced by the relevance of meaning to the decision, and by presentation modality (whether concepts were presented as words or images). In an on-line fMRI experiment, we found common regions for response inhibition across perceptual and conceptual decisions. These included the bilateral intraparietal sulcus and the right inferior frontal sulcus, whose neural responses have been linked to diverse cognitive demands in previous studies. In addition, we identified a cluster in ventral lateral occipital cortex that was sensitive to the modality of input, with a stronger response to No-Go than Go trials for meaningful images, compared to words with the same semantic content. In a second experiment, using resting-state fMRI, we explored how individual variation in the intrinsic connectivity of these activated regions related to variation in behavioural performance. Participants who showed stronger connectivity between common inhibition regions and limbic areas in medial temporal and subgenual anterior cingulate cortex were better at inhibition when this was driven by the meaning of the items. In addition, regions with a specific role in picture inhibition were more connected to a cluster in the thalamus/caudate for participants who were better at performing the picture task outside of the scanner. Together these studies indicate that the capacity to appropriately withhold action depends on interactions between common control regions, which are important across multiple types of input and decision, and other brain regions linked to specific inputs (i.e., visual features) or representations (e.g., memory).

Aging modulates fronto-temporal cortical interactions during lexical production. A dynamic causal modeling study

In this dynamic causal modeling (DCM) study, we evaluated the effect of age on the effective connectivity of a cerebral network involved in lexical production. Younger and older adults performed an object naming task during fMRI. The DCM was used to explore the interactions between four regions of interest: the occipital cortex, OC; the lateral temporal cortex, LTC; the medial temporal cortex, MTC; and the inferior frontal cortex, IFC. We mainly focused on the modulation of the fronto-temporal interaction, according to the hypothesis that aging requires strategies that modulate the access to the semantic knowledge, either through a neural reserve mechanism (increased MTC-LTC connectivity) or through a neural compensation mechanism (supplementary IFC-MTC connectivity). For younger adults, our results indicated a bi-directional interaction between the left IFC and LTC suggesting a typical activation related to lexico-semantic representations. For older adults, our results reveal the existence of bi-directional interaction between the IFC and MTC, but not between the IFC and LTC – which in turn suggests that older adults adapt a new strategy, via supplemental access to conceptual access and semantic retrieval processes. This neural compensation strategy would be facilitated by a top-down mechanism from the IFC to the MTC. We discuss our results in the context of the possible additional strategies used by older compared to younger adults, to retrieve and produce words.

Tracking the Spatiotemporal Neural Dynamics of Real-world Object Size and Animacy in the Human Brain.

Animacy and real-world size are properties that describe any object and thus bring basic order into our perception of the visual world. Here, we investigated how the human brain processes real-world size and animacy. For this, we applied representational similarity to fMRI and MEG data to yield a view of brain activity with high spatial and temporal resolutions, respectively. Analysis of fMRI data revealed that a distributed and partly overlapping set of cortical regions extending from occipital to ventral and medial temporal cortex represented animacy and real-world size. Within this set, parahippocampal cortex stood out as the region representing animacy and size stronger than most other regions. Further analysis of the detailed representational format revealed differences among regions involved in processing animacy. Analysis of MEG data revealed overlapping temporal dynamics of animacy and real-world size processing starting at around 150 msec and provided the first neuromagnetic signature of real-world object size processing. Finally, to investigate the neural dynamics of size and animacy processing simultaneously in space and time, we combined MEG and fMRI with a novel extension of MEG-fMRI fusion by representational similarity. This analysis revealed partly overlapping and distributed spatiotemporal dynamics, with parahippocampal cortex singled out as a region that represented size and animacy persistently when other regions did not. Furthermore, the analysis highlighted the role of early visual cortex in representing real-world size. A control analysis revealed that the neural dynamics of processing animacy and size were distinct from the neural dynamics of processing low-level visual features. Together, our results provide a detailed spatiotemporal view of animacy and size processing in the human brain.

MRI Characterizes the Progressive Course of AD and Predicts Conversion to Alzheimer's Dementia 24 Months Before Probable Diagnosis.

There is no disease-modifying treatment currently available for AD, one of the more impacting neurodegenerative diseases affecting more than 47.5 million people worldwide. The definition of new approaches for the design of proper clinical trials is highly demanded in order to achieve non-confounding results and assess more effective treatment. In this study, a cohort of 200 subjects was obtained from the Alzheimer’s Disease Neuroimaging Initiative. Subjects were followed-up for 24 months, and classified as AD (50), progressive-MCI to AD (50), stable-MCI (50), and cognitively normal (50). Structural T1-weighted MRI brain studies and neuropsychological measures of these subjects were used to train and optimize an artificial-intelligence classifier to distinguish mild-AD patients who need treatment (AD + pMCI) from subjects who do not need treatment (sMCI + CN). The classifier was able to distinguish between the two groups 24 months before AD definite diagnosis using a combination of MRI brain studies and specific neuropsychological measures, with 85% accuracy, 83% sensitivity, and 87% specificity. The combined-approach model outperformed the classification using MRI data alone (72% classification accuracy, 69% sensitivity, and 75% specificity). The patterns of morphological abnormalities localized in the temporal pole and medial-temporal cortex might be considered as biomarkers of clinical progression and evolution. These regions can be already observed 24 months before AD definite diagnosis. The best neuropsychological predictors mainly included measures of functional abilities, memory and learning, working memory, language, visuoconstructional reasoning, and complex attention, with a particular focus on some of the sub-scores of the FAQ and AVLT tests.

Electro-behavioral phenotype and cell injury following exposure to paraoxon-ethyl in mice: Effect of the genetic background

Organophosphorus compounds (OP) are irreversible inhibitors of both central and peripheral cholinesterases (ChE). They still represent a major health issue in some countries as well as a terrorist and military threat. In order to design appropriate medical counter-measures, a better understanding of the pathophysiology of the poisoning is needed. Little to nothing is known regarding the impact of the genetic background on OP-induced seizures and seizure-related cell injury. Using two different mouse strains, Swiss and C57BL/6J, exposed to a convulsing dose of the OP pesticide paraoxon-ethyl (POX), our study focused on seizure susceptibility, especially the occurrence of SE and related mortality. We also evaluated the initial neuropathological response and SE-induced cell injury.Following the administration of 2.4 mg/kg POX, more Swiss mice experienced SE than C57BL/6J (55.6% versus 17.2%) but the duration of their SE, based on EEG recordings, was shorter (64.3 ± 19.5 min versus 180.8 ± 36.8 min). No significant difference was observed between strains regarding mortality (33% versus 14%). In both strains limited cell injury was observed in the medial temporal cortex, the dentate gyrus and the CA3 field without inter-strain differences (Fluorojade C-positive cells/mm2). Conversely, only C57BL/6J mice showed cell injury in the CA1 field. There was no obvious correlation between the number of Fluorojade C-positive cells and the duration of the EEG discharges.Our work suggests some differences between Swiss and C57BL/6J mice and lay ground to further studies on the impact of strains in the development of central nervous system toxicity of OP.

Altered resting-state hippocampal and caudate functional networks in patients with obstructive sleep apnea.

IntroductionBrain structural injury and metabolic deficits in the hippocampus and caudate nuclei may contribute to cognitive and emotional deficits found in obstructive sleep apnea (OSA) patients. If such contributions exist, resting‐state interactions of these subcortical sites with cortical areas mediating affective symptoms and cognition should be disturbed. Our aim was to examine resting‐state functional connectivity (FC) of the hippocampus and caudate to other brain areas in OSA relative to control subjects, and to relate these changes to mood and neuropsychological scores.MethodsWe acquired resting‐state functional magnetic resonance imaging (fMRI) data from 70 OSA and 89 healthy controls using a 3.0‐Tesla magnetic resonance imaging scanner, and assessed psychological and behavioral functions, as well as sleep issues. After standard fMRI data preprocessing, FC maps were generated for bilateral hippocampi and caudate nuclei, and compared between groups (ANCOVA; covariates, age and gender).ResultsObstructive sleep apnea subjects showed significantly higher levels of anxiety and depressive symptoms over healthy controls. In OSA subjects, the hippocampus showed disrupted FC with the thalamus, para‐hippocampal gyrus, medial and superior temporal gyrus, insula, and posterior cingulate cortex. Left and right caudate nuclei showed impaired FC with the bilateral inferior frontal gyrus and right angular gyrus. In addition, altered limbic‐striatal‐cortical FC in OSA showed relationships with behavioral and neuropsychological variables.ConclusionsThe compromised hippocampal‐cortical FC in OSA may underlie depression and anxious mood levels in OSA, while impaired caudate‐cortical FC may indicate deficits in reward processing and cognition. These findings provide insights into the neural mechanisms underlying the comorbidity of mood and cognitive deficits in OSA.

Cross-sectional associations of plasma vitamin D with cerebral \u03b2-amyloid in older adults at risk of dementia

BackgroundVitamin D deficiency is associated with an increased risk of Alzheimer’s disease and increased beta-amyloid (Aβ) in animals. Hence we sought to investigate the relationship between plasma 25-hydroxyvitamin D (25(OH)D) and cerebral Aβ in older adults with subjective memory complaints.MethodsThis is a secondary analysis of the Multidomain Alzheimer Preventive Trial. Participants were 178 dementia-free individuals aged 70 years or older with data on plasma 25(OH)D and cerebral Aβ load assessed by [18F]-florbetapir positron emission tomography. Plasma 25(OH)D was measured at study baseline using a commercially available electro-chemiluminescence competitive binding assay. Standard uptake value ratios (SUVRs) were generated using the cerebellum as a reference. Brain regions assessed included the cortex, anterior cingulate, anterior putamen, caudate, hippocampus, medial orbitofrontal cortex, occipital cortex, parietal cortex, pons, posterior cingulate, posterior putamen, precuneus, semioval centre and temporal cortex. Associations were explored using fully adjusted multiple linear regression models.ResultsParticipants had a mean (SD) age of 76.2 years (4.4) and 59.6% were female. The mean (SD) plasma 25(OH)D level was 22.4 ng/ml (10.8) and the mean (SD) cortical SUVR was 1.2 (0.2). We did not find any cross-sectional associations (p > 0.05) between baseline 25(OH)D levels and Aβ in any of the brain regions studied.ConclusionsThese preliminary results suggest that circulating 25(OH)D is not associated with cerebral Aβ in older adults. Further longitudinal studies with the measurement of mid-life vitamin D status are required to explore the relationship between vitamin D and Aβ accrual over time, thereby circumventing the shortfalls of a cross-sectional study.

Hippocampal-related memory network in multiple sclerosis: A structural connectivity analysis

Background: We used graph theoretical analysis to quantify structural connectivity of the hippocampal-related episodic memory network and its association with memory performance in multiple sclerosis (MS) patients. Methods: Brain diffusion and T1-weighted sequences were obtained from 71 MS patients and 50 healthy controls (HCs). A total of 30 gray matter regions (selected a priori) were used as seeds to perform probabilistic tractography and create connectivity matrices. Global, nodal, and edge graph theoretical properties were calculated. In patients, verbal and visuospatial memory was assessed. Results: MS patients showed decreased network strength, assortativity, transitivity, global efficiency, and increased average path length. Several nodes had decreased strength and communicability in patients, whereas insula and left temporo-occipital cortex increased communicability. Patients had widespread decreased streamline count (SC) and communicability of edges, although a few ones increased their connectivity. Worse memory performance was associated with reduced network efficiency, decreased right hippocampus strength, and reduced SC and communicability of edges related to medial temporal lobe, thalamus, insula, and occipital cortex. Conclusion: Impaired structural connectivity occurs in the hippocampal-related memory network, decreasing the efficiency of information transmission. Network connectivity measures correlate with episodic memory, supporting the relevance of structural integrity in preserving memory processes in MS.

Predicted sequence of cortical tau and amyloid-β deposition in Alzheimer disease spectrum.

We investigated sequential order between tau and amyloid-β (Aβ) deposition in Alzheimer disease spectrum using a conditional probability method. Two hundred twenty participants underwent 18F-flortaucipir and 18F-florbetaben positron emission tomography scans and neuropsychological tests. The presence of tau and Aβ in each region and impairment in each cognitive domain were determined by Z-score cutoffs. By comparing pairs of conditional probabilities, the sequential order of tau and Aβ deposition were determined. Probability for the presence of tau in the entorhinal cortex was higher than that of Aβ in all cortical regions, and in the medial temporal cortices, probability for the presence of tau was higher than that of Aβ. Conversely, in the remaining neocortex above the inferior temporal cortex, probability for the presence of Aβ was always higher than that of tau. Tau pathology in the entorhinal cortex may appear earlier than neocortical Aβ and may spread in the absence of Aβ within the neighboring medial temporal regions. However, Aβ may be required for massive tau deposition in the distant cortical areas.

Optimal Readout of Correlated Neural Activity in a Decision-Making Circuit

The neural correlates of decision making have been extensively studied with tasks involving a choice between two alternatives that is guided by visual cues. While a large body of work argues for a role of the lateral intraparietal (LIP) region of cortex in these tasks, this role may be confounded by the interaction between LIP and other regions, including medial temporal (MT) cortex. Here, we describe a simplified linear model of decision making that is adapted to two tasks: a motion discrimination and a categorization task. We show that the distinct contribution of MT and LIP may indeed be confounded in these tasks. In particular, we argue that the motion discrimination task relies on a straightforward visuomotor mapping, which leads to redundant information between MT and LIP. The categorization task requires a more complex mapping between visual information and decision behavior, and therefore does not lead to redundancy between MT and LIP. Going further, the model predicts that noise correlations within LIP should be greater in the categorization compared to the motion discrimination task due to the presence of shared inputs from MT. The impact of these correlations on task performance is examined by analytically deriving error estimates of an optimal linear readout for shared and unique inputs. Taken together, results clarify the contribution of MT and LIP to decision making and help characterize the role of noise correlations in these regions.

S139. Accelerated Cortical Thinning Within Structural Brain Networks is Associated With Irritability in Youth

Irritability is an important dimension of psychopathology that spans multiple clinical diagnostic categories, yet its relationship to patterns of brain development remains sparsely explored. Here, we examined how transdiagnostic symptoms of irritability relate to the development of structural brain networks. All participants (n = 137, 83 females) completed structural brain imaging with 3 Tesla MRI at two timepoints (mean age at follow-up: 21.1 years, mean inter-scan interval: 5.2 years). Irritability at follow-up was assessed using the Affective Reactivity Index, and cortical thickness was quantified using Advanced Normalization Tools software. Structural covariance networks were delineated using non-negative matrix factorization, a multivariate analysis technique. Both cross-sectional and longitudinal associations with irritability at follow-up were evaluated using generalized additive models with penalized splines. The False Discovery Rate (q < 0.05) was used to correct for multiple comparisons. Cross-sectional analysis of follow-up data revealed that 11 of the 24 covariance networks were associated with irritability, with higher levels of irritability being associated with thinner cortex. Longitudinal analyses further revealed that accelerated cortical thinning within nine networks was related to irritability at follow-up. Effects were particularly prominent in brain regions implicated in emotion regulation, including the orbitofrontal, lateral temporal, and medial temporal cortex. Collectively, these findings suggest that irritability is associated with widespread reductions in cortical thickness and accelerated cortical thinning, particularly within the frontal and temporal cortex. Aberrant structural maturation of regions important for emotional regulation may in part underlie symptoms of irritability.

Longitudinal outcomes of amyloid positive versus negative amnestic mild cognitive impairments: a three-year longitudinal study

We aimed to compare the longitudinal outcome of amnestic mild cognitive impairment (aMCI) patients with significant Pittsburgh Compound B uptake [PiB(+) aMCI] and those without [PiB(−) aMCI]. Cerebral β-amyloid was measured in 47 patients with aMCI using PiB-positron emission tomography (PET) (31 PiB(+) aMCI and 16 PiB(−) aMCI). Clinical (N = 47) and neuropsychological follow-up (N = 37), and follow-up with brain magnetic resonance imaging (N = 38) and PiB-PET (N = 30) were performed for three years. PiB(+) aMCI had a higher risk of progression to dementia (hazard ratio = 3.74, 95% CI = 1.21–11.58) and faster rate of cortical thinning in the bilateral precuneus and right medial and lateral temporal cortices compared to PiB(−) aMCI. Among six PiB(−) aMCI patients who had regional PiB uptake ratio >1.5 in the posterior cingulate cortex (PCC), three (50.0%) progressed to dementia, and two of them had global PiB uptake ratio >1.5 at the follow-up PiB-PET. Our findings suggest that amyloid imaging is important for predicting the prognosis of aMCI patients, and that it is necessary to pay more attention to PiB(−) aMCI with increased regional PiB uptake in the PCC.

F188. THALAMIC MICROSTRUCTURE IN UNAFFECTED RELATIVES OF SCHIZOPHRENIA

BackgroundFamily, twin, adoption and candidate gene studies all support a genetic component for psychotic disorders. A considerable evidence suggests that the thalamus is abnormal in schizophrenia. The thalamus has a heterogeneous structure with its nucleus having distinct inputs and outputs. Disrupted thalamo-cortical connectivity, in particular, is considered as a core psychopathology in patients with schizophrenia. The disruption is also observed in subjects at clinical-high risk for psychosis. However, using the conventional magnetic resonance imaging methods, it had been difficult to investigate the subtle structural changes that may be present in the thalamus. Furthermore, despite the numerous reports of thalamic abnormalities in schizophrenia, the genetic aspect of the thalamic microstructure has not been thoroughly investigated.MethodsTo examine the microstructure of the thalamus, a total of 34 unaffected relatives of schizophrenia (UR) and 33 healthy control subjects underwent diffusion-weighted and diffusion kurtosis magnetic resonance imaging. Using the probabilistic tractography the projections from the thalamus to the lateral and medial prefrontal cortices, lateral and medial temporal cortices, occipital cortex, somatosensory cortex, parietal cortex and orbitofrontal cortex were analyzed. Then, the thalamus was segmented by the projections and the microstructures of those segmented regions were compared between the groups. The mean kurtosis values of the segmented regions were analyzed by analysis of covariance with age and sex as covariates and the results were adjusted with Bonferroni correction.ResultsThere was no statistical difference in the mean kurtosis values of the left and right thalamic regions projecting to any of the investigated regions between the UR and healthy controls.DiscussionOur findings, via diffusion kurtosis imaging, show preserved microstructural integrity of the thalamus in UR and that this imaging technique may be less well suited to detect thalamic abnormalities in them.

Maternal deprivation induces alterations in cognitive and cortical function in adulthood

Early life trauma is a risk factor for a number of neuropsychiatric disorders, including schizophrenia (SZ). The current study assessed how an early life traumatic event, maternal deprivation (MD), alters cognition and brain function in rodents. Rats were maternally deprived in the early postnatal period and then recognition memory (RM) was tested in adulthood using the novel object recognition task. The expression of catechol-o-methyl transferase (COMT) and glutamic acid decarboxylase (GAD67) were quantified in the medial prefrontal cortex (mPFC), ventral striatum, and temporal cortex (TC). In addition, depth EEG recordings were obtained from the mPFC, vertex, and TC during a paired-click paradigm to assess the effects of MD on sensory gating. MD animals exhibited impaired RM, lower expression of COMT in the mPFC and TC, and lower expression of GAD67 in the TC. Increased bioelectric noise was observed at each recording site of MD animals. MD animals also exhibited altered information theoretic measures of stimulus encoding. These data indicate that a neurodevelopmental perturbation yields persistent alterations in cognition and brain function, and are consistent with human studies that identified relationships between allelic differences in COMT and GAD67 and bioelectric noise. These changes evoked by MD also lead to alterations in shared information between cognitive and primary sensory processing areas, which provides insight into how early life trauma confers a risk for neurodevelopmental disorders, such as SZ, later in life.

Prior knowledge modulates the neural substrates of encoding and retrieving naturalistic events at short and long delays

Congruence with prior knowledge and incongruence/novelty have long been identified as two prominent factors that, despite their opposing characteristics, can both enhance episodic memory. Using narrative film clip stimuli, this study investigated these effects in naturalistic event memories - examining behaviour and neural activation to help explain this paradox. Furthermore, we examined encoding, immediate retrieval, and one-week delayed retrieval to determine how these effects evolve over time. Behaviourally, both congruence with prior knowledge and incongruence/novelty enhanced memory for events, though incongruent events were recalled with more errors over time. During encoding, greater congruence with prior knowledge was correlated with medial prefrontal cortex (mPFC) and parietal activation, suggesting that these areas may play a key role in linking current episodic processing with prior knowledge. Encoding of increasingly incongruent events, on the other hand, was correlated with increasing activation in, and functional connectivity between, the medial temporal lobe (MTL) and posterior sensory cortices. During immediate and delayed retrieval the mPFC and MTL each demonstrated functional connectivity that varied based on the congruence of events with prior knowledge; with connectivity between the MTL and occipital regions found for incongruent events, while congruent events were associated with functional connectivity between the mPFC and the inferior parietal lobules and middle frontal gyri. These results demonstrate patterns of neural activity and connectivity that shift based on the nature of the event being experienced or remembered, and that evolve over time. Furthermore, they suggest potential mechanisms by which both congruence with prior knowledge and incongruence/novelty may enhance memory, through mPFC and MTL functional connectivity, respectively.

Network-wise cerebral blood flow redistribution after 20 Hz rTMS on left dorso-lateral prefrontal cortex

The repetitive application of transcranial magnetic stimulation (rTMS) on left dorsolateral prefrontal cortex (DLPFC) has been consistently shown to be beneficial for treating various neuropsychiatric or neuropsychological disorders, but its neural mechanisms still remain unclear. The purpose of this study was to measure the effects of high-frequency left DLPFC rTMS using cerebral blood flow (CBF) collected from 40 young healthy subjects before and after applying 20 Hz left DLPFC rTMS or SHAM stimulations. Relative CBF (rCBF) changes before and after 20 Hz rTMS or SHAM were assessed with paired-t test. The results show that 20 Hz DLPFC rTMS induced CBF redistribution in the default mode network, including increased rCBF in left medial temporal cortex (MTC)/hippocampus, but reduced rCBF in precuneus and cerebellum. Meanwhile, SHAM stimulation didn’t produce any rCBF changes. After controlling SHAM effects, only the rCBF increase in MTC/hippocampus remained. Those data suggest that the beneficial effects of high-frequency rTMS may be through a within-network rCBF redistribution.

Recognition Memory Dysfunction Relates to Hippocampal Subfield Volume: A Study of Cognitively Normal and Mildly Impaired Older Adults.

The current study examined recognition memory dysfunction and its neuroanatomical substrates in cognitively normal older adults and those diagnosed with mild cognitive impairment (MCI). Participants completed the Mnemonic Similarity Task, which provides simultaneous measures of recognition memory and mnemonic discrimination. They also underwent structural neuroimaging to assess volume of medial temporal cortex and hippocampal subfields. As expected, individuals diagnosed with MCI had significantly worse recognition memory performance and reduced volume across medial temporal cortex and hippocampal subfields relative to cognitively normal older adults. After controlling for diagnostic group differences, however, recognition memory was significantly related to whole hippocampus volume, and to volume of the dentate gyrus/CA3 subfield in particular. Recognition memory was also related to mnemonic discrimination, a fundamental component of episodic memory that has previously been linked to dentate gyrus/CA3 structure and function. Results reveal that hippocampal subfield volume is sensitive to individual differences in recognition memory in older adults independent of clinical diagnosis. This supports the notion that episodic memory declines along a continuum within this age group, not just between diagnostic groups.