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PubMed2026

Single-cell transcriptomic atlas of Alzheimer's disease middle temporal gyrus reveals region, cell type, and sex specificity of gene expression with novel genetic risk for MERTK in female.

BackgroundAlzheimer's disease (AD), the most common age-related neurodegenerative disease, is closely associated with both amyloid-β plaque and neuroinflammation. Two thirds of AD patients are female, and they have a higher disease risk; women with AD have more extensive brain histological changes than men along with more severe cognitive symptoms and neurodegeneration.ObjectiveThis study aimed to determine how sex difference induces structural brain changes and molecular cell vulnerabilities in AD, with a focus on identifying sex-specific transcriptional alterations and genetic risk factors.MethodsWe performed single nucleus RNA sequencing on postmortem brains from individuals with AD and age- and sex-matched controls, focusing on the middle temporal gyrus, a cortical brain region strongly affected by the disease, and integrated single nucleus RNA sequencing results with genome-wide association study (GWAS) data using cell type-specific enrichment and generalized gene-set analysis approaches. The analysis pipeline is provided with threshold information.ResultsWe identified a selectively vulnerable subpopulation of layer 2/3 excitatory neurons that were RORB-negative and CDH9-expressing in both males and females. Disease-associated, but sex-independent, reactive astrocyte signatures were also present. In clear contrast, the microglia signatures of AD brains differed between males and females. Integrating single cell transcriptomic data with results from GWAS, we identified MERTK genetic variation as a candidate novel risk factor for AD selectively in females.ConclusionsTaken together, our single cell atlas of middle temporal gyrus revealed a unique cellular-level view of sex-specific transcriptional changes in AD, illuminating GWAS identification of sex-specific AD genes. These data serve as a rich resource for interrogation of the molecular and cellular basis of AD.

Alzheimer's disease↗

PubMed2023

Single-cell transcriptomic atlas of Alzheimer's disease middle temporal gyrus reveals region, cell type and sex specificity of gene expression with novel genetic risk for MERTK in female.

Alzheimer's disease, the most common age-related neurodegenerative disease, is closely associated with both amyloid-ß plaque and neuroinflammation. Two thirds of Alzheimer's disease patients are females and they have a higher disease risk. Moreover, women with Alzheimer's disease have more extensive brain histological changes than men along with more severe cognitive symptoms and neurodegeneration. To identify how sex difference induces structural brain changes, we performed unbiased massively parallel single nucleus RNA sequencing on Alzheimer's disease and control brains focusing on the middle temporal gyrus, a brain region strongly affected by the disease but not previously studied with these methods. We identified a subpopulation of selectively vulnerable layer 2/3 excitatory neurons that that were RORB-negative and CDH9-expressing. This vulnerability differs from that reported for other brain regions, but there was no detectable difference between male and female patterns in middle temporal gyrus samples. Disease-associated, but sex-independent, reactive astrocyte signatures were also present. In clear contrast, the microglia signatures of diseased brains differed between males and females. Combining single cell transcriptomic data with results from genome-wide association studies (GWAS), we identified MERTK genetic variation as a risk factor for Alzheimer's disease selectively in females. Taken together, our single cell dataset revealed a unique cellular-level view of sex-specific transcriptional changes in Alzheimer's disease, illuminating GWAS identification of sex-specific Alzheimer's risk genes. These data serve as a rich resource for interrogation of the molecular and cellular basis of Alzheimer's disease.

Journal Article↗

PubMed2026

Dual Transcranial Direct Current Stimulation Modulates Hierarchical Functional Network Organization in Post-Stroke Cognitive Impairment: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the clinical efficacy of dual transcranial direct current stimulation (tDCS) in patients with post-stroke cognitive impairment (PSCI) and to explore the effects on the hierarchical organization of functional brain networks, ranging from regional synchronization to inter-regional connectivity and global network topology. METHODS: In this randomized, double-blind, sham-controlled trial, 74 PSCI patients received conventional therapy alongside either active dual-tDCS (n = 38) or sham stimulation (n = 36). Active tDCS targeted the dorsolateral prefrontal cortex (DLPFC) via anodal-left/cathodal-right nodes (2.0 mA, 20 min/day, 20 sessions). The primary outcome was the Montreal Cognitive Assessment (MoCA). Secondary outcomes included the Mini-Mental Status Examination (MMSE), Stroop Test (ST), Trail Making Test (TMT), Wechsler Memory Scale (WMS), and Barthel Index (BI). A subgroup of 36 participants (18 per group) underwent resting-state functional magnetic resonance imaging (rs-fMRI) to analyze regional homogeneity (ReHo), functional connectivity (FC), and network topology. Partial correlations assessed the association between neuroimaging alterations and clinical improvements. RESULTS: The tDCS group showed significantly greater improvements in MoCA scores (tDCS: 5.74 ± 2.76 vs. sham: 2.69 ± 2.69; t = 4.799, p < 0.001) as well as in attention and memory domains compared to the sham group. The rs-fMRI changes included increased ReHo in the right middle temporal gyrus (MTG) and the left inferior frontal gyrus (IFG), and reduced FC between the right MTG-left superior frontal gyrus and left IFG-cerebellum (p < 0.05, FWE-corrected). Additionally, small-worldness and global efficiency increased (p < 0.05) with these alterations correlating with clinical recovery. Adverse events were rare and self-limiting. CONCLUSION: Dual-tDCS over bilateral DLPFC safely improves cognitive recovery in PSCI. These clinical gains are associated with rs-fMRI alterations, specifically in regional synchronization, inter-regional connectivity, and global topology, which suggest a potential biomarker for monitoring tDCS efficacy, offering a rationale for precision neuromodulation in stroke rehabilitation.

Humans↗

PubMed1978

An autoradiographic study of the commissural and ipsilateral hippocampo-dentate projections in the adult rat.

The distribution of the associational and commissural afferents to the inner one-fourth of the molecular layer of the dentate gyrus of the rat, has been studied autoradiographically following small injections of 3H-proline into the hilar region of the dentate (from which both groups of afferents arise). Different patterns of axonal labeling are observed after injections into the temporal (i.e., caudal), middle, or septal (rostral) thirds of the hippocampus. Thus after temporal injections labeled commissural and associational afferents are found only in the caudal third of the dentate gyrus, and the grain densities observed on the two sides are markedly asymmetrical around the short, or transverse, axis of the dentate. On the other hand, injections into the middle third of the hippocampus lead to extensive labeling of the commissural and associational afferents throughout the rostral two-thirds of the dentate gyrus, and their distribution, as judged by grain density estimates, is symmetrical on the two sides. Septal injections label fibers over the rostral half of the dentate, and again the labeling pattern on the two sides is asymmetrical (but in the reverse pattern from that seen after temporal injections). These distinctive patterns in the distribution of the two classes of afferents can generally be accounted for on the following assumptions: (1) the commissural and associational afferents share a common cytochemical specificity; (2) they compete with each other for the limited number of synaptic sites available upon the proximal portions of the granule cells: (3) the granule cells are generated along two distinct morphogenetic gradients:from the temporal to the septal pole of the dentate gyrus, and from the tip of its dorsal (or external) to the tip of its ventral (internal) blade; and (4) the first fibers to arrive monopolize the majority of the available synaptic sites, and those that reach their target field later, synapse predominantly upon the last-formed granule cell dendrites. To this extent our findings are consonant with the "temporal hypothesis" first formulated by Gottlieb and Cowan ('72). However, to account for the restricted distribution of afferents from the temporal part of the hippocampus, it is necessary to further postulate that there is some degree of topographic (or region-to-region) specificity in the ipsilateral and contralateral hippocampo-dentate projections.

Animals↗

PubMed1978

[The inscisural porencephaly of the temporal lobe and the "temporal lobe agenesis syndrome" (author's transl)].

Clinical, radiological and pathomorphological investigations on five cases offering the patterns of the so-called temporal lobe agenesis syndrome (Robinson) have shown that this is not always originally malformative, but may be due to vascular processes in the sense of porencephalic defects, with all their pathomorphological features. We think that compression of the vein of Rosenthal by inscisural hippocampal herniation is the most probable aetiological mechanism. Earle, Baldwin and Penfield also described large temporal defects in connexion with their impressive demonstration of the inscisural herniation of the hippocampal gyrus at birth. We propose to use the name of--inscisural porencephaly--for this state.

Adolescent↗

PubMed1978

Bilateral tactile aphasia: a tacto-verbal dysfunction.

Bilateral tactile aphasia was exhibited by a patient who was operated upon for a left parieto-occipital haematoma. Neuropsychological investigation established the following points: (1) the patient, in whom no expressive or receptive dysphasia could be found, misnamed objects when they were presented to him tactually, whereas he almost always gave the correct name when they were presented visually or auditorily; (2) the naming disturbance was identical when the object was presented to the left hand or to the right hand; (3) not only did the patient have no sensory deficit, but he could give unquestionable proof of correct tactile identification by using the objects presented to him tactually; (4) the defect appeared in the verbo-tactile as well as in the tacto-verbal direction; (5) it was not restricted to the name of the object since the patient was unable to describe, without making dysphasic errors, the morphology or usage of objects presented to him tactually; (6) the tacto-verbal dysfunction did not result from a tacto-visual impairment. Computerized tomography scans showed that: (1) there was no evidence suggesting a lesion of the right hemisphere, nor of the corpus callosum; (2) the left lesion involved the angular gyrus, the posterior part of the second temporal convolution, the inferior longitudinal fasciculus, the geniculostriate fibres and some fibres of the tapetum.

Agnosia↗

PubMed1978

[Responses of neurons of hypothalamic nuclei to stimulation of the frontobasal regions of the neocortex].

Neuronal responses of different hypothalamic nuclei to frontobasal cerebral cortex (proreal, posterior orbital, basal and temporal regions) were studied in acute experiments on cats narcotized by membutal mixed with chloraloze. Neurons which could be activated antidromically during stimulation of another region were recorded. On the basis of their response a number of neuronal chains (circles) functioning in forebrain was distinguished. The first chain is orbital gyrus--preoptical zone--proreal gyrus. The second chain has the same cortical components as the first one, but switching over in the hypothalamus takes place in the region of mamillary bodies. The third chain is basal temporal cortex--lateral hypothalamus--prefrontal cortex.

Animals↗

PubMed1979

Intraluminal diameters of middle cerebral branches for microanastomoses.

Intraluminal diameter measurements of the branches of the middle cerebral artery were taken from 50 adult human cerebral hemispheres of a routine autopsy service. The measurements were confined to the cortical branches found on the surface of the brain located over the lateral hemisphere, with the center at the transverse gyrus of Heschl and extending over the circular portion of the brain, with a diameter of approximation 6 cm. It was hoped that these measurements would assist in the appropriate choice of artery for microanastomosis in the superficial temporal artery bypass procedure, now being done for enhancement of cortical perfusion.

Brain Ischemia↗

PubMed1979

Unilateral inferior temporal lobectomy with hippocampectomy for relief of incisural herniation.

1. The syndrome of incisural hippocampal herniation, accompanied by unilateral and then bilateral fixed pupils, deepening coma, respiratory irregularity (Cheyne-Stokes), contralateral hemiplegia, ipsilateral decerebrate posturing rising blood pressure, and finally renal shutdown, indicates a terminal state that requires immediate relief. 2. Accepted methods of relief by brain shrinkage, dexamethasone, subtemporal decompression, anterior temporal lobectomy, cutting of the tentorium, and even massive uncapping of the skull, have failed in the author's experience to reverse the process when once established. 3. Presentation is made of a rapid and relatively simple inferior horizontal temporal lobectomy, including the hippocampal gyrus, so as to relieve peduncle compression, blockage of cerebrospinal fluid circulation, midbrain haemorrhage, and infarction in the posterior cerebral artery distribution area. 4. Reports are given of 15 cases out of 30 cases in which operation proved lifesaving, with restoration of normal function in 13. 5. Those patients who died did so in an average of five days, and generally showed either no herniation or continuing evidence of tumour or internal bleeding. 6. Very young patients particularly have an excellent chance of survival, which is seven times better than that of adults in having good to excellent results without operation.

Adolescent↗

PubMed1975

Effects of stereotactic cingulumotomy on a sequential motor task in man.

The effect of bilateral cingulumotomy on sequential tapping behavior was investigated in 6 patients, Contrary to previous clinical studies and predictions derived from data on cingulate lesions in the rat, a consistent decrement in postoperative performance was not found. Temporal integration of behavior in man, as measured in terms of accuracy of sequential motor performance, does not appear to be critically dependent upon the integrity of the cingulum bundle at the level of interruption investigated in the present study.

Adult↗

PubMed1978

On magnopyramidal temporal fields in the human brain - probable morphological counter parts of Wernicke's sensory speech region.

Posterior parts of the human superior temporal gyrus have been examined by means of stereomicroscopical observations of pigment preparations up to 800 microgram thick. As a rule, the proximal half of the first transverse gyrus of Heschl is covered by an extremely lightly pigmented conicortex which is surrounded by belt areas, a proncoinocortex anteriorly and paraconiocortical fields posteriorly and laterally. The paraconiocortex is divisble into a primitively organized part lying just behind the conicortical core and a more advanced portion forming the temporal magnopyramidal region. This extended lateralmost part of the paraconicortex is more or less richly endowed with unusually large and pigment-rich IIIc-pyramids. Third layer pyramidal cells showing densley aggregated lipofuscin deposits are rarely encountered within the human isocortex. As regards the temporal lobe, pyramids of this type, in general, do not occur outside the magnopyramidal region. The magnopyramidal region covers only a part of the temporal plane but extends much more in the lateral direction spreading over distal portions of the first and the second transverse gyri, posterior parts of the exposed surface of the superior temporal gyrus and those of its lower wall. The extension of the magnopyramidal region varies considerably from one side of the brain to the other. It is also subject to a pronounced variation from one individual to another. On account of its localization and its uniqueness in cortical structure, the temporal magnopyramidal region is considered to represent the morphological counterpart of the sensory speech centre of Wernicke.

Aged↗

PubMed1977

Alexia without agraphia, hemianopia, or color-naming defect: a disconnection syndrome.

A patient with alexia without agraphia, hemianopia, or color-naming defect was found at operation to have a meningioma arising from the tentorium cerebelli that compressed the inferior aspect of the left temporal-occipital junction. It is presumed to have involved only the left ventral visual association cortex and its inferior outflow tracts to the angular gyrus. The input from the right occipital area also was disconnected from the visual language verbal association area by involvement of the ventral outflow of the splenium of the corpus callosum. Preservation of color naming and matching suggests that these functions are dependent on the integrity of more dorsal occipital association systems.

Brain Neoplasms↗

PubMed1978

Limbic lobe involvement in presenile dementia.

Limbic lobe involvement in presenile dementia was studied from a neuropathological and neuropsychiatric viewpoint. The material consisted of seven cases of Alzheimer's disease, four cases of Pick's disease, and four cases of Jacob-Creutzfeldt's disease. These three groups showed different patterns of distribution of the degeneration characteristic for each group, in particular for the first two. Among the groups, these patterns differed with regard to involvement both of nonlimbic and limbic areas. Thus the Alzheimer group had a mainly temporoparieto-occipital and posterior cingulate gyrus involvement. The Pick group in many respects showed an inverse distribution with frontotemporal and anterior cingulate gyrus accentuation of the damage. Basal temporal limbic areas were involved in both groups. The Jacob-Creutzfeldt group had a less schematic lesion pattern, without involvement of limbic areas. From a neuropsychiatric aspect, these differences were reflected in symptoms that could be referred both to areas spared and those more pronouncedly destroyed by the degenerative process. Thus the Alzheimer group long retained emotional qualities that were lost early in the Pick group. The possible relationship between neurotransmitters and regional accentuation of the degeneration is discussed.

Aged↗

PubMed2026

Changes in hippocampal functional connectivity and volume associated with cognitive improvement and decline in amnestic mild cognitive impairment following computerized cognitive training.

BACKGROUND: The hippocampus influences the outcomes of amnestic mild cognitive impairment (aMCI) and undergoes different changes during the cognitive decline or recovery of aMCI compared to elderly individuals with normal cognition, which may reveal disease-dependent neurodegeneration or plasticity. We first aimed to investigate the hippocampal changes associated with cognitive changes in aMCI using a combined case-control study design. METHODS: In total, 50 aMCI individuals and 50 healthy controls (HCs) were recruited in Shenyang, China, and separately randomized into training and control groups: aMCI training group, aMCI no training group, HC training group, and HC no training group. The aMCI and HC training groups received computerized cognitive training (CCT) thrice weekly for 12 weeks. Cognitive assessments and MRI data were collected at baseline and follow-up. RESULTS: The primary outcome was significant CCT×diagnosis interaction effect on the change in cognitive performance as measured by clock drawing test (CDT) scores (F = 4.322, P = 0.041); this interaction was driven by CCT specifically in aMCI (F = 4.465, P = 0.038). Significant CCT×diagnosis interaction effects of right-hippocampal FC changes were observed in the bilateral precuneus/cuneus (Pvoxel<0.05) driven by CCT in aMCI (F = 5.429, P = 0.023), and in the left superior temporal gyrus/middle temporal gyrus (STG/MTG, Pvoxel<0.05), driven by CCT of only in HCs (F = 6.587, P = 0.013). A significant interaction effect of left-hippocampal FC changes were observed in the right triangular part of the inferior frontal gyrus (IFGtriang, Pvoxel<0.05), driven by CCT in aMCI and HCs (F = 6.550, P = 0.013; F = 7.097, P = 0.010). No significant interaction effect on the change in hippocampal GMV was noted (P > 0.05). CONCLUSION: CCT can improve the visuospatial ability of aMCI, which is reflected by the CDT scores. CCT can alter hippocampal FC in the bilateral precuneus/cuneus, the right IFGtriang, and the left STG/MTG. The hippocampal GMV is difficult to change in both HCs and aMCI during the cognitive decline. REGISTRATION NUMBER: ChiCTR1900026849. DATE OF REGISTRATION: 24 October 2019 NAME OF TRIAL REGISTRY: Chinese Clinical Trial Registry (ChiCTR).

Humans↗

PubMed1979

Cortical activation pattern during saccadic eye movements in humans: localization by focal cerebral blood flow increases.

Regional cerebral blood flow (rCBF) was measured in human subjects during saccadic eye movements by a 254-channel dynamic gamma camera. Focal rCBF increases were repeatedly observed in an area within the middle precentral and premotor regions which corresponds to the frontal eye field in humans. Our findings suggest that this region is localized between the "face" and "hand" areas in the precentral gyrus and extends anteriorly out of the primary motor strip into the adjacent premotor zone. In addition, saccades were associated with focal blood flow increases in regions corresponding to the frontal supplementary motor area and to the posterior temporooccipital visual association cortex. Similar changes in patterns of rCBF occurred during contralateral and ipsilateral horizontal saccades and also during vertical saccades, and did not differ between the right and left hemispheres. Focal rCBF increases were observed in the frontal eye field during several additional test procedures including ocular fixation and visual perception of a nonmoving target, auditory stimulation with closed eyes, and reading. It is presumed that these focal flow increases reflect increased localized neuronal activity and metabolic rate and therefore permit visualization of the cortical activation pattern associated with saccadic eye movements in humans.

Cerebral Cortex↗

PubMed2026

Theta-range SEEG stimulation for intracranial mapping: extending conventional 1-Hz and 50-Hz protocols.

OBJECTIVE: Electrical brain stimulations (EBS) are central to epileptic network identification and functional mapping during stereo-electroencephalography, yet stimulation frequencies remain empirical, and standardized across patients and brain regions, producing false negatives and false positives, and potentially compromising surgical outcome. We prospectively investigated theta-range EBS (7 Hz) in the temporal lobe, a prominent physiological frequency band in this region, and compared it with conventional 1-Hz and 50-Hz protocols. METHODS: We analyzed 1,408 temporal EBS in 25 drug-resistant epileptic patients. Epileptic responses (afterdischarges, seizures) and clinical signs were assessed across the epileptic network and temporal structures (amygdala, hippocampus, neocortex, parahippocampal gyrus, white matter), and confronted to stimulation parameters (frequency, intensity, duration, total charge). RESULTS: At matched intensity and duration, 7-Hz EBS were associated with a higher occurrence of afterdischarges and clinical signs than 1-Hz EBS in several temporal structures. Effects on usual seizure induction were less consistent. Comparisons with 50 Hz showed no systematic significant differences, with responses observed at one or both frequencies depending on structure and outcome. When controlling for total charge, frequency-related differences were attenuated. Some effects were sporadically observed at both intermediate frequency and charge quantity. CONCLUSIONS: EBS responses emerge from the interaction between all electrical parameters and anatomical location and local excitability, and can hardly be disentangled. However, 7-Hz EBS can provide complementary clinical information during temporal-lobe mapping, with a targeted approach. SIGNIFICANCE: These findings support targeted evaluation of broader stimulation parameter spaces, including intermediate frequencies, rather than routine reliance on fixed low- and high-frequency protocols alone.

Humans↗

PubMed2025

A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study.

BACKGROUND: Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group. METHODS: T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9). RESULTS: PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges' g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges' g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (p corrected  = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (p corrected  = .001). CONCLUSIONS: PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

Humans↗