The posterior parahippocampal gyrus (PPHG) of the non-human primate brain has a distinct dual role in cortical neural systems. On the one hand, it is a critical link in providing the entorhinal cortex and hippocampal formation with cortical input, while on the other hand it receives output from these structures and projects widely by disseminating the medial temporal lobe output to the cortex. Layer III of TF and TH areas largely mediate the former (input) while layer V mediates the latter (output). We have examined areas TF and TH in the normal human brain and in Alzheimer's disease (AD) using pathological stains (Nissl, Thioflavin S) and phenotype specific stains non-phosphorylated neurofilament protein (SMI32) and parvalbumin (PV). Seven clinically and pathologically confirmed AD cases have been studied along with six age-compatible normal cases. Our observations reveal that neurofibrillary tangles (NFTs) heavily invest the area TF and TH neurons that form layers III and V. In both cortical areas, the large pyramids that form layer V contain a greater number of NFTs. These changes, and possibly, pyramidal cell loss, greatly alter the cytoarchitectural picture and diminish SMI32 staining patterns. Layer III of area TH loses the majority of SMI32 immunoreactivity, whereas this change is more conspicuous in layer V of area TF. PV-staining in both areas is largely unaffected. Normal cases contained no evidence of pathology or altered cytoarchitecture. These observations reveal a further disruption of memory-related temporal neural systems in AD where pathology selectively alters both the input to the hippocampal formation and its output to the cortex.

The CHAT gene encodes choline acetyltransferase, which is an enzyme responsible for the biosynthesis of the neurotransmitter acetylcholine in the brain. This study collected structural MRI, genetic, and behavioral data from 324 healthy Chinese adults, and examined the associations between CHAT genetic variants, parahippocampal and hippocampal structure, and short-term memory span. After controlling for intracranial volume, sex, and age, CHAT SNP rs12246528 had the strongest association with parahippocampal structure, with the A allele being linked to smaller volume, surface area, and thickness. SNP rs1917814 had the strongest association with hippocampal volume, with the T allele being linked to larger hippocampal volume. After controlling for sex and age, CHAT rs3729496 had the strongest association with memory span, with the T allele being associated with a greater memory span. Finally, the left parahippocampal gyrus surface area was positively associated with memory span. This study provides the first evidence for the involvement of the CHAT gene in parahippocampal and hippocampal structures and memory span in healthy Chinese adults.

Accumulating evidence suggests that a disruption of zinc (Zn) homeostasis may play a role in the pathogenesis of Alzheimer's disease. Although several Zn transporter proteins responsible for the regulation of Zn balance are present in the brain, there has been little study of these proteins in Alzheimer's disease. To determine if alterations of Zn transporter proteins exist, levels of Zn transporter-4, which functions to remove Zn from the cytoplasm to endosomal/lysosomal compartments, and Zn transporter-6, which allocates cytoplasmic Zn to the trans-Golgi network, were measured in the hippocampus/parahippocampal gyrus, superior and middle temporal gyrus, and cerebellum of subjects with mild cognitive impairment, early Alzheimer's disease, late stage Alzheimer's disease, and age-matched controls using Western blot analysis and protein specific antibodies. Our results show that Zn transporter-4 and Zn transporter-6 are significantly (P<0.05) increased in hippocampus/parahippocampal gyrus of early Alzheimer's disease and Alzheimer's disease subjects. Zn transporter-6 is also increased (P<0.1) in the superior and middle temporal gyrus of Alzheimer's disease brain.

Of current obesity treatments, bariatric surgery induces the most weight loss. Given the marked increase in the number of bariatric surgeries performed, elucidating the mechanisms of action is a key research goal. We compared whole brain activation in response to high-energy dense (HED) vs. low-energy dense (LED) visual and auditory food cues before and approximately 4 months after Roux-en-Y Gastric Bypass (RYGB) (n = 16) and Sleeve Gastrectomy (SG) (n = 9). We included two control groups: a low-calorie diet weight loss group (WL) (n = 14) and a non-treatment group (NT) (n = 16). Relative to the control groups, the surgery groups showed increased dorsolateral prefrontal cortex (dlPFC) and decreased parahippocampal/fusiform gyrus (PHG/fusiform) activation in response to HED vs. LED, suggesting greater cognitive dietary inhibition and decreased rewarding effects and attention related to HED foods. dlPFC activation was significantly more increased in RYGB vs. SG. We also found that postprandial increases in GLP-1 concentrations (pre to postsurgery) correlated with postsurgical decreases in RYGB brain activity in the inferior temporal gyrus and the right middle occipital gyrus in addition to increases in the right medial prefrontal gyrus/paracingulate for HED > LED stimuli, suggesting involvement of these attention and inhibitory regions in satiety signaling postsurgery.

Functional plasticity of the adult brain is well established. Recently, the structural counterpart to such plasticity has been suggested by neuroimaging studies showing experience-dependent differences in gray matter (GM) volumes. Within the primary and secondary olfactory cortices, reduced GM volumes have been demonstrated in patients with olfactory loss. However, these cross-sectional studies do not provide causal evidence for GM volume change, and thereby structural plasticity. Disorders of the peripheral olfactory system, such as chronic rhinosinusitis (CRS), provide an ideal model to study GM structural plasticity, given that patients may experience long periods of olfactory impairment, followed by near complete recovery with treatment. We therefore performed a prospective longitudinal study in patients undergoing surgical treatment for CRS. We used voxel-based morphometry (VBM) to investigate GM volume change in 12 patients (M:F = 7:5; 47.2 ± 14.9 years), 3 months post-op. There was a significant improvement in olfactory function according to birhinal psychophysical testing. We performed a voxel-wise region of interest analysis, with significance corrected for number of regions (p < 0.0036corr). We found significantly increased post-operative GM volumes within the primary (left piriform cortex, right amygdala) and secondary (right orbitofrontal cortex, caudate nucleus, hippocampal-parahippocampal complex and bilateral temporal poles) olfactory networks, and decreased GM volumes within the secondary network only (left caudate nucleus and temporal pole, bilateral hippocampal-parahippocampal complex). As a control measure, we assessed GM change within V1, S1 and A1, where there were no suprathreshold voxels. To our knowledge, this is the first study to demonstrate GM structural plasticity within the primary and secondary olfactory cortices, following restoration of olfaction.

Mild cognitive impairment (MCI) represents a transitional state between normal aging and Alzheimer's disease (AD). Non-invasive diagnostic methods are desirable to identify MCI for early therapeutic interventions. In this study, we proposed a support vector machine (SVM)-based method to discriminate between MCI patients and normal controls (NCs) using multi-level characteristics of magnetic resonance imaging (MRI). This method adopted a radial basis function (RBF) as the kernel function, and a grid search method to optimize the two parameters of SVM. The calculated characteristics, i.e., the Hurst exponent (HE), amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo) and gray matter density (GMD), were adopted as the classification features. A leave-one-out cross-validation (LOOCV) was used to evaluate the classification performance of the method. Applying the proposed method to the experimental data from 29 MCI patients and 33 healthy subjects, we achieved a classification accuracy of up to 96.77%, with a sensitivity of 93.10% and a specificity of 100%, and the area under the curve (AUC) yielded up to 0.97. Furthermore, the most discriminative features for classification were found to predominantly involve default-mode regions, such as hippocampus (HIP), parahippocampal gyrus (PHG), posterior cingulate gyrus (PCG) and middle frontal gyrus (MFG), and subcortical regions such as lentiform nucleus (LN) and amygdala (AMYG). Therefore, our method is promising in distinguishing MCI patients from NCs and may be useful for the diagnosis of MCI.

Visual-related cortex plays an important role in the process of movement. It is of great importance to clarify whether traumatic spinal cord injury (SCI), which is a typical disease that results in sensorimotor dysfunction, leads to the alteration of visual-related brain structure and function area. To address this issue, multimodality MRI was applied on eleven patients with acute incomplete cervical cord injury (ICCI) and eleven healthy controls (HCs) to explore possible structural and functional changes of the brain. Voxel-based morphometry (VBM) analysis was performed to investigate the changes in brain structure of ICCI patients. The fractional amplitude of low-frequency fluctuations (fALFF) was used to characterize changes in regional neural activities, and independent component analysis (ICA) was carried out to explore alterations in the resting-state networks (RSNs) after ICCI. We also investigated correlations among brain imaging metrics and between the metrics and clinical variables. Compared with HCs, ICCI patients exhibited significant gray matter atrophy in the left hippocampus and parahippocampal gyrus, right superior frontal gyrus (SFG), and middle frontal gyrus (MFG) and also a decrease in fALFF in the left orbitofrontal cortex (OFC). Moreover, ICCI patients exhibited decreased intra-network functional connectivity (FC) in the medial vision network (mVN). The mean fALFF value was correlated with clinical motor scores of the left extremities and the total motor scores. Our findings proved that ICCI can not only cause structural changes in visual-related brain regions, but also result in visual-related brain functional alterations, revealing the possible mechanism of the effects of visual feedback training in motor function rehabilitation of SCI patients.

Despite significant advances, the neural correlates and neurochemical mechanisms involved in performance monitoring and behavioral adaptation are still a matter for debate. Here, we used a modified Eriksen-Flanker task in a magnetic resonance imaging (MRI) study that required the participants to derive the correct stimulus-response association based on a feedback given after each flanker stimulus. Participants had to continuously monitor and adapt their performance as the stimulus-response association switched after a jittered time interval without notice. After every switch an increase of reaction times was observed. At the neural level, the feedback indicating the need to switch was associated with activation of the precuneus, the cingulate cortex, the insula and a brainstem region tentatively identified as the locus coeruleus. This brainstem system appears to interact with this cortical network and seems to be essential for performance monitoring and behavioral adaptation. In contrast, the cerebellum crus and prefrontal areas are activated during error feedback processing. Furthermore we found activations of the hippocampus and parahippocampal gyrus bilaterally after a correct feedback in learnable stimulus-response associations. These results highlight the contribution of brainstem nuclei to performance adaptation.

Activity of the immediate early genes c-fos and zif268 was compared across hemispheres in rats with unilateral, excitotoxic lesions of the hippocampus (dentate gyrus and CA fields 1-4). Counts of the protein products of these genes were made shortly after rats performed a test of spatial working memory in the radial-arm maze, a task that is sensitive to bilateral lesions of the hippocampus. Unilateral hippocampal lesions produced evidence of widespread hypoactivity. Significant reductions in immediate early gene counts were observed within all three anterior thalamic nuclei, as well as the entorhinal, perirhinal, and postrhinal cortices, and much of the subicular complex. In contrast, no observable changes were detected in the anterior cingulate, infralimbic or prelimbic cortices, as well as several amygdala nuclei, even though many of these regions receive projections from the subiculum. Instead, the immediate early gene changes were closely linked to sites that are thought to be required for successful task performance, with both immediate early genes giving similar patterns of results. The findings support the notion that the anterior thalamic nuclei, hippocampus, and parahippocampal cortices form the key components of an interdependent neuronal network involved in spatial mnemonic processing.

Histamine is known to be a neurotransmitter in the brain, but it has not been clearly implicated in major diseases. All histaminergic neurons reside in the posterior hypothalamus and innervate most brain areas, which is compatible with the concept that histamine is involved in general central regulatory mechanisms. A sensitive high-performance liquid chromatographic fluorimetric method was used to measure histamine contents in post mortem Alzheimer brains and age-matched controls. The cellular storage sites and distribution of histaminergic nerve fibers were examined with a specific immunohistochemical method. The histamine content was significantly reduced in the hypothalamus (42% of control value), hippocampus (43%) and temporal cortex (53%) of Alzheimer brains. Differences in other cortical areas, putamen and substantia nigra were not significant. Histamine-containing nerve fibers were found in the hippocampus, parahippocampal gyrus and subiculum of both Alzheimer brains and controls. No histamine-containing mast cells were seen in these temporal structures. Histamine in the human temporal lobe is stored in nerve fibers originating from the posterior hypothalamus, and not in mast cells. Decrease in brain histamine may contribute to the cognitive decline in Alzheimer's disease directly or through the cholinergic system. Development of drugs that penetrate the blood brain barrier and increase histaminergic activity might be beneficial in Alzheimer's disease.

The pancreatitis-associated protein (PAP) family (also known as the regenerating gene (Reg) family) is a group of 16 kDa secretory proteins structurally classified as the calcium dependent-type lectin superfamily. Some PAP family members are expressed in neurons following peripheral nerve injury and traumatic brain injury. To determine whether PAP family members are expressed in non-traumatic brain injury, expressions were analyzed following kainic acid (KA)-induced seizure. PAP-I (also known as Reg2 in rat and RegIII-beta in mouse) and pancreatitis associated protein-III (PAP-III; RegIII-gamma in mouse) messenger ribonucleic acid (mRNA) was transiently expressed in some restricted areas, such as the hippocampus and parahippocampal area; expression was observed immediately at a maximal level 1 day after seizure. Expression disappeared within 3 days after seizure. In situ hybridization (ISH) and immunohistochemistry revealed neuronal PAP-I and PAP-III expression in the hippocampal dentate gyrus, perirhinal and entorhinal cortices, and the posterior cortical nucleus of the amygdala. The number of PAP-III mRNA-positive neurons was significantly greater than PAP-I mRNA-positive neurons. The majority of positive neurons co-localized with c-Jun, but not with glutamic acid decarboxylase (GAD). These results may suggest that PAP-I and PAP-III induction in non-GABAergic neurons would protect neurons against damage following seizure.

The precuneus, involved in various cognitive processes, is considered to form the midline core of the default mode network (DMN), while the medial temporal lobe (MTL) is a subsystem of the DMN. Until now, the anatomical study of the precuneus-MTL connection is limited in humans. One possible reason is the precuneus' territory of the posteromedial cortex (PMC) is inconsistent across studies. The primary purpose of this study is to investigate the structural connectivity (SC) of precuneus-MTL, focusing on its anatomical organization using the Human Connectome Project Multi-modal Parcellation (HCP MMP) atlas. We first conducted the quantitative tractography analyses using the HCP dataset. The major streamlines originated from the posterior precuneus and were projected to the MTL extensively. Next, to complement the tractography data, we conducted the white matter dissection in the post-mortem human brain. We observed the major fiber bundles arise from the posterior precuneus extending to the anterior parahippocampal gyrus, which could support our tractography results. Then we analyzed the relationship between SC and resting-state functional connectivity (rsFC) of the precuneus-MTL. Although the SC-rsFC correlation was scarce on the whole, the posterior precuneus (POS2, 7Pm, 7m) showed a relatively high correlation (r = 0.38349, p < 0.05) with the posterior MTL (PreS, H, ProS, PHA1, PHA2). Our findings suggest the posterior precuneus is highly connected to MTL structurally, which could have an effect on the resting-state functional connectivity. In addition, the precuneus might consist of the heterogeneous connectivity-based subdivisions.

Physical exercises and motor skill learning have been shown to induce changes in regional brain morphology, this has been demonstrated for various activities and tasks. Also individuals with special skills show differences in regional brain morphology. This has been indicated for professional musicians, London taxi drivers, as well as for athletes like dancers, golfers and judokas. However little is known about whether sports with different metabolic profiles (aerobic vs. anaerobic) are associated with different patterns of altered brain morphology. In this cross-sectional study we investigated two groups of high-performance athletes, one group performing sports that are thought to be mainly aerobic, and one group performing sports known to have intermittent phases of anaerobic metabolism. Using high-resolution structural imaging and voxel-based morphometry (VBM), we investigated a group of 26 male athletes consisting of 13 martial artists and 13 endurance athletes as well as a group of non-exercising men (n=13). VBM analyses revealed higher gray matter (GM) volumes in the supplementary motor area/dorsal premotor cortex (BA 6) in both athlete groups as compared to the control group. In addition, endurance athletes showed significantly higher GM volume in the medial temporal lobe (MTL), specifically in the hippocampus and parahippocampal gyrus, which was not seen in the martial arts group. Our data suggest that high-performance sports are associated with changes in regional brain morphology in areas implicated in motor planning and motor learning. In addition high-level endurance sports seem to affect MTL structures, areas that have previously been shown to be modulated by aerobic exercise.

Some meditation techniques teach the practitioner to achieve the state of mental silence. The aim of this study was to investigate brain regions that are associated with their volume and functional connectivity (FC) with the depth of mental silence in long-term practitioners of Sahaja Yoga Meditation. Twenty-three long-term practitioners of this meditation were scanned using Magnetic Resonance Imaging. In order to identify the neural correlates of the depth of mental silence, we tested which gray matter volumes (GMV) were correlated with the depth of mental silence and which regions these areas were functionally connected to under a meditation condition. GMV in medial prefrontal cortex including rostral anterior cingulate cortex were positively correlated with the subjective perception of the depth of mental silence inside the scanner. Furthermore, there was significantly increased FC between this area and bilateral anterior insula/putamen during a meditation-state specifically, while decreased connectivity with the right thalamus/parahippocampal gyrus was present during the meditation-state and the resting-state. The capacity of long-term meditators to establish a durable state of mental silence inside an MRI scanner was associated with larger gray matter volume in a medial frontal region that is crucial for top-down cognitive, emotion and attention control. This is furthermore corroborated by increased FC of this region during the meditation-state with bilateral anterior insula/putamen, which are important for interoception, emotion, and attention regulation. The findings hence suggest that the depth of mental silence is associated with medial fronto-insular-striatal networks that are crucial for top-down attention and emotional control.