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Results for “dorsolateral prefrontal cortex”

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PubMed1990

Vertical and horizontal coding of space in the monkey dorsolateral prefrontal cortex.

Single cell activity in the dorsolateral prefrontal cortex was recorded in a monkey performing a delayed alternation (DA) task in 3 directions, to the left, to the right, and upwards. Among the 127 units studied in all three directions, 18 neurons were spatially selective in one direction (to the left, to the right or upwards), 37 neurons in two directions and 8 neurons in each 3 directions during the performance of the DA task. Of the 9 neurons that were spatially selective upwards, 8 had a specific pattern of activity during the delay period and one during the response period. When several spatial directions are studied in a DA task, as in this work, it becomes evident that the prefrontal cortex contains a large number of spatially selective neurons. The results of this study suggest that there is a spatial memory map in the prefrontal cortex which is needed not only when a DA task is performed to the left and to the right but also in the upward direction.

Animals↗

PubMed1978

Functional development of the dorsolateral prefrontal cortex: an analysis utlizing reversible cryogenic depression.

The dorsolateral prefrontal cortex of rhesus monkeys was functionally inactivated by local hypothermia as the monkeys performed spatial delayed-response and spatial delayed-alternation tasks at different stages of postnatal development. Cryogenic depression of prefrontal cortex at a temperature sufficient to induce 21--25% decrements in delayed-response performance in 34--36-month-old-monkeys, produced deficits of only 7--8% in 19--31-month-old and no detectable loss in younger monkeys, 9--16 months of age. Delayed-alternation performance was impaired by local hypothermia as early as 8.5 months of age, but maximal cooling-induced deficits on this task were not observed before 33 months of age. Thermal gradients mapped in representative monkeys at different stages of development were remarkable similar, indicating that the age-dependent differences in behavior were not attributable to technical factors. The results obtained in the present study on normal developing monkeys confirm the interpretation of previous research on brain-damaged infants that functional maturation of the dorsolateral prefrontal cortex is protracted over several years of postnatal life, and extends the earlier studies by indicating that the lower limit for maturity of dorsolateral function is close to puberty in this species. Further, the present study revealed that delayed-response and delayed-alternation performance are dissociable dorsolateral functions which achieve maturity at different rates. The convergence of evidence from reversible neural depression and permanent lesion methods provides strong validation for neurobehavioral analysis as a general approach to the study of regional maturation of the brain.

Age Factors↗

PubMed1976

Delayed-matching and delayed-response deficit from cooling dorsolateral prefrontal cortex in monkeys.

The hypothesis that the functional integrity of the dorsolateral prefrontal cortex is important for short-term memory of both spatial and nonspatial information was examined. Monkeys were tested in delayed matching-to-sample (DMS) and delayed-response (DR) tasks with delays of 0-32 sec. Testing was carried out under three different conditions: frontal cooling (FC), parietal cooling (PC), and normal temperature (noncooling, NC). Errors, reaction time, and motor activity were recorded. The proportion of correct responses decreased in NC as a function of the delay. This decrease was significantly accentuated by FC, whereas it was not modified by PC. At each delay, the decrement elicited by FC was as large in DR as in DMS. Reaction time and activity normally increased as a function of delay; these changes were enhanced by FC. The FC-induced decrements in proportion of correct responses suggest a faster loss from short-term memory of both spatial and nonspatial information.

Animals↗

PubMed1978

Dorsolateral prefrontal cortex lesions and discrimination of movement-produced cues by rhesus monkeys.

Rhesus monkeys were trained on a conditional discrimination in which sequences of either 32 or 64 lever presses served as discriminative stimuli. For half the subjects, reinforcement was contingent upon choice of a red response key following a sequence of 32 presses (FR 32), and a white key after FR 64, with the position of the two key colors randomized across trials. The remaining subjects were reinforced for left key presses after FR 64, and right key presses after FR 32, with key color again randomized across trials. Ablation of dorsolateral prefrontal cortex resulted in postoperative deficits in all subjects, although 6 of 8 eventually remastered the task. This recovery was investigated in a second experiment, in which psychophysical functions were generated by varying the length of the shorter FR. Although dorsolateral lesions again produced a severe disruption in performance, the post-operative functions eventually obtained were identical to the preoperative functions. This pattern of marked impairment in retention of fixed ratio discriminations, but no change in asymptotic capacity, suggests participation of dorsolateral prefrontal cortex in processing kinesthetic information, possibly analogous to the role of inferior temporal cortex in processing visual information.

Animals↗

PubMed1992

The dorsolateral prefrontal cortex, schizophrenia and PET.

Central neurophysiology can be measured with PET. These measurements are providing insights into the regional abnormalities associated with schizophrenia. Cohorts of schizophrenic subjects have been studied cross-sectionally in attempts to identify common regional deficits. More recently the advent of fast dynamic measurements of regional cerebral blood flow have allowed rapid serial measurements in the same subject in different brain states (activation studies). These complementary approaches are based upon, and are interpreted with reference to, a number of methodological considerations and underlying hypotheses. The key hypotheses underpinning cross-sectional and activation studies are discussed within the framework of the lesion model and functional anatomy models of brain function. This brief review of some assumptions, ideas and methodological constraints is illustrated with empirical data implicating the dorsolateral prefrontal cortex in schizophrenic symptoms.

Behavior↗

PubMed1978

The effect of ambient illumination on delayed-matching and delayed-response deficits from cooling dorsolateral prefrontal cortex.

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Animals↗

PubMed1991

Neuronal activity related to saccadic eye movements in the monkey's dorsolateral prefrontal cortex.

1. Single-neuron activity was recorded from the prefrontal cortex of monkeys performing saccadic eye movements in oculomotor delayed-response (ODR) and visually guided saccade (VGS) tasks. In the ODR task the monkey was required to maintain fixation of a central spot throughout the 0.5-s cue and 3.0-s delay before making a saccadic eye movement in the dark to one of four or eight locations where the visual cue had been presented. The same locations were used for targets in the VGS tasks; however, unlike the ODR task, saccades in the VGS tasks were visually guided. 2. Among 434 neurons recorded from prefrontal cortex within and surrounding the principal sulcus (PS), 147 changed their discharge rates in relation to saccadic eye movements in the ODR task. Their response latencies relative to saccade initiation were distributed between -192 and 460-ms, with 22% exhibiting presaccadic activity and 78% exhibiting only postsaccadic activity. Among PS neurons with presaccadic activity, 53% also had postsaccadic activity when the monkey made saccadic eye movements opposite to the directions for which the presaccadic activity was observed. 3. Almost all (97%) PS neurons with presaccadic activity were directionally selective. The best direction and tuning specificity of each neuron were estimated from parameters used to fit a Gaussian tuning curve function. The best direction for 62% of the neurons with presaccadic activity was toward the contralateral visual field, with the remaining neurons having best directions toward the ipsilateral field (23%) or along the vertical meridian (15%). 4. Most postsaccadic activity of PS neurons (92%) was also directionally selective. The best direction for 48% of these neurons was toward the contralateral visual field, with the remaining neurons having best directions toward the ipsilateral field (36%) or along the vertical meridian (16%). Eighteen percent of the neurons with postsaccadic activity showed a reciprocal response pattern: excitatory responses occurred for one set of saccade directions, whereas inhibitory responses occurred for roughly the opposite set of directions. 5. Sixty PS neurons with saccade-related activity in the ODR task were also examined in a VGS task. Forty of these neurons showed highly similar profiles of directional specificity and response magnitude in both tasks, 13 showed saccade-related activity only in the ODR task, and 7 changed their response characteristics between the ODR and VGS tasks.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2026

Neurometabolites and Antipsychotic Response in Psychosis: A Mega-Analysis.

IMPORTANCE: Revealing neurobiological markers of antipsychotic nonresponse in psychosis may aid outcome prediction and inform novel treatment targets. OBJECTIVE: To examine differences in neurometabolites in antipsychotic nonresponsive compared to antipsychotic-responsive psychosis using individual participant data and meta-analysis. DATA SOURCES: Web of Science was searched for studies published between January 1, 1980, and November 1, 2025. Authors of 21 eligible studies identified before August 2024 were invited to contribute individual participant data. STUDY SELECTION: Eighteen studies examining neurometabolites by treatment response in psychosis contributed individual participant data for the mega-analysis. These studies plus a further 5 studies were included in the meta-analyses of standardized mean differences and variability. DATA EXTRACTION AND SYNTHESIS: Individual participant data were analyzed using linear mixed models with study as a random effect. Subgroup analyses examined prospective designs and treatment-resistant samples. Published group means and standard deviations were extracted for meta-analyses. MAIN OUTCOMES AND MEASURES: Group differences in glutamate, glutamate plus glutamine, choline, myo-inositol, N-acetylaspartate, γ-aminobutyric acid, and glutathione in the medial frontal cortex, dorsolateral prefrontal cortex, thalamus, and basal ganglia. RESULTS: The mega-analysis included 1189 participants from 18 studies; of these, 476 were treatment nonresponders (mean [SD] age, 33.0 [12.5] years; 340 male), 427 were treatment responders (mean [SD] age, 30.3 [11.5] years; 299 male), and 286 were healthy control individuals (mean [SD] age, 31.0 [12.5] years; 170 male). Compared with the antipsychotic response group, nonresponders showed elevations in medial frontal glutamate (Glass Δ = 0.21; P = .02), glutamate plus glutamine (Glass Δ = 0.29; P = .002), choline (Glass Δ = 0.22; P = .03), and myo-inositol (Glass Δ = 0.35; P = .001); similar elevations were observed relative to control individuals. Elevated medial frontal glutamate plus glutamine in antipsychotic nonresponders compared with responders was also observed prospectively in first-episode psychosis (Glass Δ = 0.41; P = .002), whereas myo-inositol elevations were greatest in individuals meeting criteria for treatment-resistance (Glass Δ = 0.64; P = .001). The meta-analysis of 23 studies (1844 participants) also showed elevated medial frontal choline and myo-inositol in antipsychotic nonresponse compared with response. CONCLUSIONS AND RELEVANCE: These findings provide evidence of an association between antipsychotic nonresponse in psychosis with elevations in medial frontal glutamate, choline, and myo-inositol. The presence of elevations in these markers supports the continued investigation of glutamate-acting and inflammatory pathway-associated interventions for psychosis and schizophrenia.

Humans↗

PubMed2026

BDNF-DT and BDNF-AS-DT: novel genes in the BDNF locus.

Divergent transcription from bidirectional promoters is frequently observed in eukaryotic genomes, but the biological relevance of divergent RNA transcripts (DT) is unknown. We identified and characterized BDNF-DT, a novel DT gene, and BDNF-AS-DT, a novel readthrough gene, in the locus containing BDNF, a gene with key roles in neuronal development, differentiation, and synaptic plasticity. BDNF-DT is independent from the known BDNF antisense (BDNF-AS), and its expression is developmentally regulated and positively correlated with BDNF in human postmortem dorsolateral prefrontal cortex (DLPFC). BDNF-DT and BDNF-AS-DT expression increase after induced depolarization, but the temporal dynamics follow expression of BDNF, suggesting a regulatory role. Moreover, CRISPR-mediated upregulation of BDNF in human neural progenitor cells drives BDNF-DT expression. Finally, BDNF-DT shows higher expression in DLPFC from patients diagnosed with schizophrenia compared to neurotypical controls, and genetically predicted lower expression of the BDNF-AS-DT readthrough transcript is associated with schizophrenia and with the schizophrenia-associated C allele of the rs6265 single-nucleotide polymorphism. These findings identify BDNF-DT and BDNF-AS-DT as novel, low-abundance genes that show coordinated expression with BDNF and association with schizophrenia risk, though their biological significance requires further validation given detection limitations and the need to establish causal roles.

Humans↗

PubMed1991

The organization of serotonergic projections to cerebral cortex in primates: retrograde transport studies.

Retrograde axonal transport and immunocytochemical methods were utilized to determine the origin of serotonergic afferents to selected primary projection and association areas of cerebral cortex in macaque monkeys. After injections of Fast Blue or Diamidino Yellow in primary motor, somatosensory, or visual cortex, retrogradely labeled neurons are found in both the dorsal and median raphe nuclei. The sets of dorsal raphe neurons which innervate these cortical areas differ in their spatial distributions along the rostrocaudal axis of the brainstem; a coarse rostrocaudal topographic relationship is found between these groups of dorsal raphe neurons and their cortical targets. In contrast, neurons in the median raphe which innervate these primary projection areas are not differentially distributed along the rostrocaudal axis. However, in both the median and dorsal raphe nuclei, most neurons projecting to primary visual cortex are situated lateral to the cells which project to motor and somatosensory areas; many of these visually projecting neurons lie among the fascicles of the medial longitudinal fasciculus. For comparison with the serotonergic innervation of primary projection areas, the locations of raphe cells projecting to three areas of association cortex were examined: dorsolateral prefrontal cortex, area 5 and area 7b. Neurons projecting to each of these association areas are found throughout the dorsal and median raphe nuclei. Their distributions are similar to one another; however, more cells projecting to dorsolateral prefrontal cortex are in the rostral part of the dorsal raphe. The dorsal and median raphe neurons projecting to these association areas are intermingled with neurons projecting to motor and somatosensory cortex, but are medial to most of those projecting to visual cortex. Thus, separate cortical areas are innervated by different sets of raphe neurons; these sets partially overlap, yet differ in their rostrocaudal and mediolateral distributions. Ascending serotonergic projections to cerebral cortex form a widely distributed system which exhibits a highly intricate anatomic organization. The present observations support the hypothesis that the dorsal raphe nucleus is comprised of distinct sets of neurons whose output is distributed to multiple, interconnected cortical areas; these serotonergic projections may play a role in the coordination of excitability in functionally related areas of cortex. In contrast, the serotonergic projections arising from the median raphe appear to be more divergent and are likely to have a global influence on cortical activity. Since these individual raphe nuclei have different projection patterns, they are likely to have distinct functional roles.

Afferent Pathways↗

PubMed1991

The role of the inferior prefrontal convexity in performance of delayed nonmatching-to-sample.

Findings in an earlier study (Bachevalier, J. and Mishkin, M. Behav. Brain Res. 20, 249-261, 1986) indicated that ventromedial prefrontal cortex, which receives thalamic projections from the limbo-diencephalic system, is critical for visual recognition; whereas the dorsolateral prefrontal cortex, which receives no such thalamic projections, makes little or no contribution to this type of memory. In the present study, we examined the role in recognition of another prefrontal area outside the thalamic projection zone of the limbo-diencephalic system, namely, the inferior prefrontal convexity. In the first experiment, monkeys with lesions of this cortex (Group IC) were found to be impaired in relearning delayed nonmatching-to-sample (DNMS), but not on the subsequent DNMS performance test in which memory demands were greatly increased. In a second experiment, monkeys with combined lesions of the inferior and dorsolateral prefrontal cortex (Group LAT) were also found to be impaired in relearning DNMS, but in this case they were impaired, in addition, on the subsequent performance test. Neither group (IC or LAT) showed retardation in acquiring visual discrimination habits. Analysis of the DNMS behavior of both groups suggested that their deficits on this task were due not to a loss in recognition memory, but to various forms of perseverative interference. The results support the view that the inferior prefrontal convexity, like the dorsolateral prefrontal cortex, lies outside the limbo-diencephalic memory system not only anatomically but also functionally.

Animals↗

PubMed1978

Neuronal plasticity in primate telencephalon: anomalous projections induced by prenatal removal of frontal cortex.

When the dorsolateral prefrontal cortex in one hemisphere of a rhesus monkey is resected 6 weeks before birth and the fetus survives to postnatal ages, neurons of the corresponding cortex in the intact hemisphere issue a greatly expanded projection to the contralateral caudate nucleus in addition to a normal projection to the ipsilateral caudate. The enhancement of the crossed prefronto-caudate pathway after prenatal neurosurgery provides direct evidence for lesion-induced neuronal rearrangement in the primate telencephalon.

Animals↗

PubMed2026

Neurophysiological signatures of Stanford Neuromodulation Therapy in treatment resistant depression.

Treatment-resistant depression (TRD) affects approximately 30% of patients with major depressive disorder. Stanford Neuromodulation Therapy (SNT), a high-dose intermittent theta-burst transcranial magnetic stimulation protocol, produces rapid antidepressant effects, but its neurophysiological mechanisms remain unclear. Here, we used longitudinal TMS-EEG to characterize the progressive neurophysiological changes induced by SNT, assess their site-specificity, and explore whether baseline neural markers are associated with clinical response. We conducted a double-blind, randomized, sham-controlled trial at Stanford University (2017-2018; analysis August 2024-October 2025) in 24 TMS-naïve participants with TRD (Montgomery-Åsberg Depression Rating Scale ≥20; ≥1 failed antidepressant trial). Participants were randomized to active (n = 12) or sham (n = 12) SNT, consisting of 10 sessions per day over 5 consecutive days targeting the left dorsolateral prefrontal cortex (90,000 pulses). TMS-EEG was acquired at two baseline sessions, before and after each treatment session, and at 1-month follow-up (14 TMS-EEG sessions in total). Active SNT progressively reduced cortical excitability at the treatment site, with significant decreases by day 3 in the early window component (-27.9%; P < 0.01), while no changes were observed at the vertex control site. Site-specific comparisons confirmed early window reductions only at the left dorsolateral prefrontal cortex (t₂₂ = -3.82; P < 0.001). SNT also selectively decreased estimated medial prefrontal source activity consistent with the subgenual anterior cingulate cortex (sgACC) across sessions (F₁₃,₂₂₂ = 4.93; P < 0.001), with effects persisting at 1-month follow-up. In an exploratory analysis in the active group (n = 12), higher baseline estimated sgACC source activity was associated with greater clinical improvement (r = -0.67; P = 0.023); although promising, the latter preliminary finding requires replication in larger, adequately powered samples before predictive utility can be established. These findings indicate that SNT induces progressive, site-specific cortical modulation and selective downstream effects on estimated sgACC source activity. Early cortical excitability changes represent candidate neurophysiological markers of SNT response, while the observed association between baseline sgACC activity and clinical outcome, while preliminary, motivates prospective investigation of subcortical source activity as a potential predictor of treatment response in larger trials. ClinicalTrials.gov Identifier: NCT03068715.

Journal Article↗

PubMed2025

Impact of Chewing Behavior Change on Cognition and Cerebral Hemodynamics.

BACKGROUND: Impaired chewing ability is a recognized risk factor for cognitive decline in older adults, potentially due to reduced neural stimulation in cognition-related brain regions. While short-term studies have demonstrated transient increases in neural activity from chewing, the sustained cognitive and neurophysiological effects of encouraging thorough chewing habits in daily life remain unclear. OBJECTIVE: This randomized controlled trial investigated whether promoting thorough chewing during meals could improve cognitive function and cerebral hemodynamics in older adults. METHODS: Fifty participants aged 65 y or older were randomly assigned to either a 1-mo intervention group, which used a wearable device to monitor and increase chewing strokes during meals, or a control group that maintained usual chewing habits. Chewing behavior, cognitive performance (including memory and executive function via the color Stroop test), and cerebral hemodynamics in the dorsolateral prefrontal cortex (DLPFC) were measured at baseline and after 1 mo. Statistical analyses included t tests, chi-square tests, 2-way analysis of variance with post hoc tests, Pearson correlations, and generalized linear models to evaluate group differences and associations between chewing and cognitive outcomes. RESULTS: Significant time-by-group interactions were observed for memory, F(1, 48) = 6.24, P = 0.043, and hemodynamic responses in the left DLPFC, F(1, 48) = 6.19, P = 0.013. The intervention group showed increased chewing frequency (P = 0.017), improved memory performance, and reduced left DLPFC responses compared with controls. Chewing frequency was positively correlated with Stroop test scores (r = 0.53, P = 0.010) and negatively with hemodynamic changes in the left DLPFC (r = -0.30, P = 0.040). Although improvements in other cognitive outcomes and hemodynamic measures favored the intervention group, these differences did not reach statistical significance. CONCLUSIONS: Promoting intentional chewing habits for 1 mo may enhance memory-related cognitive performance and neural efficiency in the DLPFC during working memory tasks in older adults. This nonpharmacologic, low-burden strategy warrants further research with longer interventions to support cognitive health and dementia prevention. TRIAL REGISTRATION ID: UMIN000044280Knowledge Transfer Statement:This study demonstrates that promoting thorough chewing habits in older adults can improve memory and enhance neural efficiency in the brain. Encouraging intentional mastication is a simple, nonpharmacologic approach that may help maintain cognitive health and prevent dementia, providing a practical strategy for clinicians and policymakers to support healthy aging.

Humans↗

PubMed1992

Schizophrenics show spatial working memory deficits.

The present study demonstrates that schizophrenics are impaired on spatial delayed-response tasks, analogous to those that have been used to assess the working memory function of the dorsolateral prefrontal cortex in rhesus monkeys. Schizophrenic patients and two control groups, normal subjects and bipolar psychiatric patients, were tested on the oculomotor version of the memory task, a haptic version of the same task, and two control tasks: a sensory task that did not require working memory and a digit span test. The schizophrenic patients showed marked deficits relative to the two control groups in both the oculomotor and haptic delayed-response tasks. They were not, however, impaired on the digit span test, which taps verbal working memory as well as voluntary attention, and on the sensory control task, in which their responses were guided by external cues rather than by spatial working memory. These findings provide direct evidence that schizophrenics suffer a loss in representational processing and that this deficit is modality independent. These data on spatial working memory add to the growing evidence for involvement of the dorsolateral prefrontal cortex in schizophrenic disease.

Adult↗

PubMed2026

Multiomic single-nucleus profiling reveals cell-type-specific epigenetic and transcriptional dysregulation in major depressive disorder brain.

OBJECTIVE: Major depressive disorder (MDD) is a leading global cause of disability, marked by persistent mood disturbances, cognitive deficits, and changes in prefrontal cortex neural circuitry. In this study, we aimed to define cell-type-specific molecular and regulatory mechanisms underlying MDD by mapping gene-expression and chromatin-accessibility changes in the dorsolateral prefrontal cortex (PFC) (dlPFC). METHODS: Postmortem dlPFC (BA9) tissue from 7 MDD and 8 well-matched controls was analyzed using 10× Genomics snRNA-seq and paired ATAC+RNA multiome sequencing. Sequencing data were processed with Cell Ranger pipelines, nuclei were filtered for quality and doublets/debris, and datasets were integrated and clustered using Seurat/Signac packages. Differential gene expression, chromatin accessibility, and transcription factor motif activity were tested between MDD and controls within each cell type, followed by peak-to-gene linkage and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and PsyGeNET enrichment to interpret dysregulated regulatory mechanisms. RESULTS: A total of 20 distinct clusters encompassing major neuronal and non-neuronal populations were identified. Differential analyses uncovered extensive cell type-specific changes in chromatin accessibility and gene expression, particularly within excitatory layer 5/6 and inhibitory Pvalb neurons, as well as glial and vascular populations. Functional enrichment indicated dysregulation of synaptic organization, neurotransmission, myelination, stress-response, and immune-regulatory pathways across neuronal and non-neuronal cells. Notably, glucocorticoid-responsive transcription factors NR3C1/NR3C2 exhibited conserved regulatory networks implicating stress signaling in MDD pathophysiology. CONCLUSIONS: Together, these findings provide a comprehensive single-nucleus atlas of gene regulation in the MDD PFC, highlighting coordinated dysfunction across neurons, glia, and vascular cells.

Major Depressive Disorder↗

PubMed1991

Cortical control of reflexive visually-guided saccades.

Reflexive visually-guided saccade triggering may be facilitated or inhibited by the cerebral cortex. To study this control, saccades made towards suddenly appearing visual targets (saccade task) or away from them (antisaccade task) were recorded electro-oculographically in 45 patients with limited unilateral cerebral infarction. Lesions affected (1) the superior part of the angular gyrus (area 39 of Brodmann) in the posterior parietal cortex (PPC), (2) the dorsolateral prefrontal cortex (PFC) (area 46 of Brodmann), (3) the frontal eye field (FEF), or (4) the supplementary motor area (SMA). As these 4 types of lesions were located either in the right or the left cerebral hemisphere, patients were divided into 8 groups. Saccade latency, in the saccade task, and the percentage of errors (misdirected saccades made towards the visual target), in the antisaccade task, were compared in each group of patients with the values of 20 control subjects. In the saccade task, saccade latency was significantly increased bilaterally in the right PPC group. In the left PPC group, the increase in latency was less marked, and significant only for saccades made contralaterally to the lesion. In the different frontal groups, latency was unchanged or only slightly increased. These results confirm that the main area facilitating the triggering of reflexive visually-guided saccades is located in the PPC, in or near the superior part of the angular gyrus. The difference between right and left parietal lesions could be due to the predominance of the right hemisphere in the control of these saccades. In the antisaccade task, the percentage of errors was significantly increased bilaterally in both PFC groups compared with the control group and also to the FEF and SMA groups. These results suggest that the PFC is the main area in the cerebral hemisphere inhibiting reflexive visually-guided saccades.

Cerebral Cortex↗

PubMed2026

Cross-tissue immune profiling of APOE ε4 reveals early dysregulation in Alzheimer's disease.

INTRODUCTION: Apolipoprotein E (APOE) ε4 is the strongest genetic risk factor for late-onset Alzheimer's disease (AD), but its contribution to disease pathogenesis remains incompletely understood. METHODS: Here, we integrate proteomic profiling of plasma (n = 9028), cerebrospinal fluid (n = 1099), dorsolateral prefrontal cortex (n = 720), and superior temporal gyrus (n = 105) to define the immune phenotype associated with APOE ε4. RESULTS: We identify a conserved, allele dose-dependent pro-inflammatory immune protein signature across peripheral and central tissues independent of AD diagnosis. This signature also emerges in patient-derived cortical organoids prior to amyloid beta and tau pathology, supporting a genotype-driven mechanism. Cross-tissue comparisons reveal shared innate and antiviral responses alongside tissue-specific immune signaling. Notably, a 12-week medical ketogenic diet partially reversed the APOE ε4 immune signature. DISCUSSION: These findings position immune dysregulation as an early and tractable driver of AD risk in APOE ε4 carriers with direct implications for targeted prevention strategies.

Humans↗