Medial Temporal Area Research Articles

Neural substrate for the engagement of the ventral visual stream in motor control in the macaque monkey.

The present study aimed to describe the cortical connectivity of a sector located in the ventral bank of the superior temporal sulcus in the macaque (intermediate area TEa and TEm [TEa/m]), which appears to represent the major source of output of the ventral visual stream outside the temporal lobe. The retrograde tracer wheat germ agglutinin was injected in the intermediate TEa/m in four macaque monkeys. The results showed that 58-78% of labeled cells were located within ventral visual stream areas other than the TE complex. Outside the ventral visual stream, there were connections with the memory-related medial temporal area 36 and the parahippocampal cortex, orbitofrontal areas involved in encoding subjective values of stimuli for action selection, and eye- or hand-movement related parietal (LIP, AIP, and SII), prefrontal (12r, 45A, and 45B) areas, and a hand-related dysgranular insula field. Altogether these data provide a solid substrate for the engagement of the ventral visual stream in large scale cortical networks for skeletomotor or oculomotor control. Accordingly, the role of the ventral visual stream could go beyond pure perceptual processes and could be also finalized to the neural mechanisms underlying the control of voluntary motor behavior.

Coupled oscillations orchestrate selective information transmission in visual cortex.

Performing visually guided behavior involves flexible routing of sensory information towards associative areas. We hypothesize that in visual cortical areas, this routing is shaped by a gating influence of the local neuronal population on the activity of the same population's single neurons. We analyzed beta frequencies (representing local population activity), high-gamma frequencies (representative of the activity of local clusters of neurons), and the firing of single neurons in the medial temporal (MT) area of behaving rhesus monkeys. Our results show an influence of beta activity on single neurons, predictive of behavioral performance. Similarly, the temporal dependence of high-gamma on beta predicts behavioral performance. These demonstrate a unidirectional influence of network-level neural dynamics on single-neuron activity, preferentially routing relevant information. This demonstration of a local top-down influence unveils a previously unexplored perspective onto a core feature of cortical information processing: the selective transmission of sensory information to downstream areas based on behavioral relevance.

Examining the neurostructural architecture of intelligence: The Lothian Birth Cohort 1936 study

Examining underlying neurostructural correlates of specific cognitive abilities is practically and theoretically complicated by the existence of the positive manifold (all cognitive tests positively correlate): if a brain structure is associated with a cognitive task, how much of this is uniquely related to the cognitive domain, and how much is due to covariance with all other tests across domains (captured by general cognitive functioning, also known as general intelligence, or ‘g’)? We quantitatively address this question by examining associations between brain structural and diffusion MRI measures (global tissue volumes, white matter hyperintensities, global white matter diffusion fractional anisotropy and mean diffusivity, and FreeSurfer processed vertex-wise cortical volumes, smoothed at 20mm fwhm) with g and cognitive domains (processing speed, crystallised ability, memory, visuospatial ability). The cognitive domains were modelled using confirmatory factor analysis to derive both hierarchical and bifactor solutions using 13 cognitive tests in 697 participants from the Lothian Birth Cohort 1936 study (mean age 72.5 years; SD = .7). Associations between the extracted cognitive factor scores for each domain and g were computed for each brain measure covarying for age, sex and intracranial volume, and corrected for false discovery rate.There were a range of significant associations between cognitive domains and global MRI brain structural measures (r range .008 to .269, p < .05). Regions implicated by vertex-wise regional cortical volume included a widespread number of medial and lateral areas of the frontal, temporal and parietal lobes. However, at both global and regional level, much of the domain-MRI associations were shared (statistically accounted for by g). Removing g-related variance from cognitive domains attenuated association magnitudes with global brain MRI measures by 27.9–59.7% (M = 46.2%), with only processing speed retaining all significant associations. At the regional cortical level, g appeared to account for the majority (range 22.1–88.4%; M = 52.8% across cognitive domains) of regional domain-specific associations. Crystallised and memory domains had almost no unique cortical correlates, whereas processing speed and visuospatial ability retained limited cortical volumetric associations. The greatest spatial overlaps across cognitive domains (as denoted by g) were present in the medial and lateral temporal, lateral parietal and lateral frontal areas.

The influence of the precuneus on the medial temporal cortex determines the subjective quality of memory during the retrieval of naturalistic episodes.

Memory retrieval entails dynamic interactions between the medial temporal lobe and areas in the parietal and frontal cortices. Here, we tested the hypothesis that effective connectivity between the precuneus, in the medial parietal cortex, and the medial temporal cortex contributes to the subjective quality of remembering objects together with information about their rich spatio-temporal encoding context. During a 45min encoding session, the participants were presented with pictures of objects while they actively explored a virtual town. The following day, under fMRI, participants were presented with images of objects and had to report whether: they recognized the object and could remember the place/time of encoding, the object was familiar only, or the object was new. The hippocampus/parahippocampus, the precuneus and the ventro-medial prefrontal cortex activated when the participants successfully recognized objects they had seen in the virtual town and reported that they could remember the place/time of these events. Analyses of effective connectivity showed that the influence exerted by the precuneus on the medial temporal cortex mediates this effect of episodic recollection. Our findings demonstrate the role of the inter-regional connectivity in mediating the subjective experience of remembering and underline the relevance of studying memory in contextually-rich conditions.

Distinct Cortical Networks Subserve Spatio-temporal Sampling in Vision through Different Oscillatory Rhythms.

Although visual input arrives continuously, sensory information is segmented into (quasi-)discrete events. Here, we investigated the neural correlates of spatiotemporal binding in humans with magnetoencephalography using two tasks where separate flashes were presented on each trial but were perceived, in a bistable way, as either a single or two separate events. The first task (two-flash fusion) involved judging one versus two flashes, whereas the second task (apparent motion: AM) involved judging coherent motion versus two stationary flashes. Results indicate two different functional networks underlying two unique aspects of temporal binding. In two-flash fusion trials, involving an integration window of ∼50 msec, evoked responses differed as a function of perceptual interpretation by ∼25 msec after stimuli offset. Multivariate decoding of subjective perception based on prestimulus oscillatory phase was significant for alpha-band activity in the right medial temporal (V5/MT) area, with the strength of prestimulus connectivity between early visual areas and V5/MT being predictive of performance. In contrast, the longer integration window (∼130 msec) for AM showed evoked field differences only ∼250 msec after stimuli offset. Phase decoding of the perceptual outcome in AM trials was significant for theta-band activity in the right intraparietal sulcus. Prestimulus theta-band connectivity between V5/MT and intraparietal sulcus best predicted AM perceptual outcome. For both tasks, phase effects found could not be accounted by concomitant variations in power. These results show a strong relationship between specific spatiotemporal binding windows and specific oscillations, linked to the information flow between different areas of the where and when visual pathways.

Effects of the perceived temporal distance of events on mental time travel and on its underlying brain circuits.

Mental Time Travel (MTT) allows us to remember past events and imagine future ones. According to previous literature, the Temporal Distance of events affects MTT: our ability to order events worsens for close, compared to far, events. However, those studies established distances a-priori, albeit the way we perceive events' temporal distance may subjectively differ from their objective distance. Thus, in the current study, we aimed to investigate the effects of Perceived Temporal Distance (PTD) on the MTT ability and the brain areas mediating this process. Thirty-three healthy volunteers took part in an fMRI MTT task. Participants were asked to project themselves into the past, present, or future, and to judge a series of events as relative-past or relative-future, in relation to the adopted time location. Outside the scanner, participants provided PTD estimates for each stimulus of the MTT task. Participants' performance and functional activity were analyzed as a function of these estimations. At the behavioural level, PTD predicts the modulation of the performance for relative-past and relative-future. Bilateral angular gyrus, retrosplenial cortex, temporo-parietal region and medial, middle and superior frontal gyri mediate the PTD effect. In addition to these areas, the closer the relative-future events are perceived, the higher the involvement of left parahippocampal and lingual gyri and right cerebellum. Thus, perceived proximity of events activates frontal and posterior parietal areas, which therefore might mediate the processing of PTD in the cognitive spatial representation of time. Future proximity also activates cerebellum and medial temporal areas, known to be involved in imaginative and constructive cognitive functions.

Cardiorespiratory fitness is associated with cortical thickness of medial temporal brain areas associated with spatial cognition in young but not older adults.

Cardiorespiratory fitness has a potent effect on neurocognitive health, especially regarding the hippocampal memory system. However, less is known about the impact of cardiorespiratory fitness on medial temporal lobe extrahippocampal neocortical regions. Specifically, it is unclear how cardiorespiratory fitness modulates these brain regions in young adulthood and if these regions are differentially related to cardiorespiratory fitness in young versus older adults. The primary goal of this study was to investigate if cardiorespiratory fitness predicted medial temporal lobe cortical thickness which, with the hippocampus, are critical for spatial learning and memory. Additionally, given the established role of these cortices in spatial navigation, we sought to determine if cardiorespiratory fitness and medial temporal lobe cortical thickness would predict greater subjective sense of direction in both young and older adults. Cross-sectional data from 56 young adults (20-35 years) and 44 older adults (55-85 years) were included. FreeSurfer 6.0 was used to automatically segment participants' 3T T1-weighted images. Using hierarchical multiple regression analyses, we confirmed significant associations between greater cardiorespiratory fitness and greater left entorhinal, left parahippocampal, and left perirhinal cortical thickness in young, but not older, adults. Left parahippocampal cortical thickness interacted with age group to differentially predict subjective sense of direction in young and older adults. Young adults displayed a positive, and older adults a negative, correlation between left parahippocampal cortical thickness and sense of direction. Our findings extend previous work on the association between cardiorespiratory fitness and hippocampal subfield structure in young adults to left medial temporal lobe neocortical regions.

CSF Aβ42/40 is associated with neurodegeneration independently of CSF p‐tau in the earliest AD continuum

AbstractBackgroundSoluble Aβ dyshomeostasis is thought to be the earliest detectable alteration in AD, but is believed to have little impact on neurodegeneration. Conversely, the onset of tau pathology in the presence of Aβ drives subsequent neurodegeneration. Here, we aimed to assess the independent contribution of soluble Aβ and tau dyshomeostasis to neurodegeneration, in the earliest stages of the AD continuum.MethodThe first 330 consecutive participants of the ALFA+ study with available longitudinal (3.45±0.24 y) MRI, CSF Aβ42, Aβ40, p‐tau181, and NfL at baseline were included. CSF biomarkers were assessed with the Roche NeuroToolKit robust prototype immunoassays and p‐tau181 with the Elecsys® Phospho‐Tau (181P) CSF immunoassay (Roche Diagnostics International Ltd). Gray matter volume (GMv) changes were computed voxelwise using SPM12 on T1w scans. Hippocampal subfields were segmented using ASHS on high‐resolution acquisitions. To detect regions showing early neurodegeneration, correlations between CSF NfL and GMv changes were sought. Then, GMv and hippocampal subfields changes were sought in association with CSF Aβ42/40 and CSF p‐tau181, both alone and after controlling for the other biomarkers. The interactive effect of CSF p‐tau181 and Aβ status (CSF Aβ42/40 &lt; 0.071) on brain structure was determined.ResultTable 1 shows sample’s characteristics. CSF NfL concentrations were associated with longitudinal GMv atrophy in the medial and inferior temporal areas (Fig. 1A). CSF Aβ42/40 significantly predicted GMv atrophy in the hippocampus bilaterally, alone and when controlling for CSF p‐tau181 and NfL (Fig. 1B‐C). CSF p‐tau181 interacted with Aβ status to predict GMv atrophy in the posterior hippocampus bilaterally (Fig. 1D). Longitudinal GMv atrophy in the hippocampal subfields were confirmed in association with CSF Aβ42/40 in the bilateral CA1, dentate gyrus and BA35 (Table 2).ConclusionIndependently of p‐tau, early Aβ dyshomeostasis is associated with longitudinal GMv atrophy in AD‐sensitive brain areas in the early AD continuum. As expected, tau levels were associated with additional atrophy in these regions in Aβ+ individuals. Pathophysiological alterations other than Aβ, but correlated with CSF Aβ levels, might contribute to the observed atrophy patterns. Control of the earliest pathophysiological alterations in AD may have a relevant impact on neurodegeneration, even at the earliest preclinical stages.

On the functional brain networks involved in tool-related action understanding

Tool-use skills represent a significant cognitive leap in human evolution, playing a crucial role in the emergence of complex technologies. Yet, the neural mechanisms underlying such capabilities are still debated. Here we explore with fMRI the functional brain networks involved in tool-related action understanding. Participants viewed images depicting action-consistent (e.g., nail-hammer) and action-inconsistent (e.g., scarf-hammer) object-tool pairs, under three conditions: semantic (recognizing the tools previously seen in the pairs), mechanical (assessing the usability of the pairs), and control (looking at the pairs without explicit tasks). During the observation of the pairs, task-based left-brain functional connectivity differed within conditions. Compared to the control, both the semantic and mechanical conditions exhibited co-activations in dorsal (precuneus) and ventro-dorsal (inferior frontal gyrus) regions. However, the semantic condition recruited medial and posterior temporal areas, whereas the mechanical condition engaged inferior parietal and posterior temporal regions. Also, when distinguishing action-consistent from action-inconsistent pairs, an extensive frontotemporal neural circuit was activated. These findings support recent accounts that view tool-related action understanding as the combined product of semantic and mechanical knowledge. Furthermore, they emphasize how the left inferior parietal and anterior temporal lobes might be considered as hubs for the cross-modal integration of physical and conceptual knowledge, respectively.

Inhibitory TMS over Visual Area V5/MT Disrupts Visual Speech Recognition.

During face-to-face communication, the perception and recognition of facial movements can facilitate individuals' understanding of what is said. Facial movements are a form of complex biological motion. Separate neural pathways are thought to processing (1) simple, nonbiological motion with an obligatory waypoint in the motion-sensitive visual middle temporal area (V5/MT); and (2) complex biological motion. Here, we present findings that challenge this dichotomy. Neuronavigated offline transcranial magnetic stimulation (TMS) over V5/MT on 24 participants (17 females and 7 males) led to increased response times in the recognition of simple, nonbiological motion as well as visual speech recognition compared with TMS over the vertex, an active control region. TMS of area V5/MT also reduced practice effects on response times, that are typically observed in both visual speech and motion recognition tasks over time. Our findings provide the first indication that area V5/MT causally influences the recognition of visual speech.SIGNIFICANCE STATEMENT In everyday face-to-face communication, speech comprehension is often facilitated by viewing a speaker's facial movements. Several brain areas contribute to the recognition of visual speech. One area of interest is the motion-sensitive visual medial temporal area (V5/MT), which has been associated with the perception of simple, nonbiological motion such as moving dots, as well as more complex, biological motion such as visual speech. Here, we demonstrate using noninvasive brain stimulation that area V5/MT is causally relevant in recognizing visual speech. This finding provides new insights into the neural mechanisms that support the perception of human communication signals, which will help guide future research in typically developed individuals and populations with communication difficulties.

Evidence for adaptive myelination of subcortical shortcuts for visual motion perception in healthy adults.

Conscious visual motion information follows a cortical pathway from the retina to the lateral geniculate nucleus (LGN) and on to the primary visual cortex (V1) before arriving at the middle temporal visual area (MT/V5). Alternative subcortical pathways that bypass V1 are thought to convey unconscious visual information. One flows from the retina to the pulvinar (PUL) and on to medial temporal visual area (MT); while the other directly connects the LGN to MT. Evidence for these pathways comes from non-human primates and modest-sized studies in humans with brain lesions. Thus, the aim of the current study was to reconstruct these pathways in a large sample of neurotypical individuals and to determine the degree to which these pathways are myelinated, suggesting information flow is rapid. We used the publicly available 7T (N = 98; 'discovery') and 3T (N = 381; 'validation') diffusion magnetic resonance imaging datasets from the Human Connectome Project to reconstruct the PUL-MT (including all subcompartments of the PUL) and LGN-MT pathways. We found more fibre tracts with greater density in the left hemisphere. Although the left PUL-MT path was denser, the bilateral LGN-MT tracts were more heavily myelinated, suggesting faster signal transduction. We suggest that this apparent discrepancy may be due to 'adaptive myelination' caused by more frequent use of the LGN-MT pathway that leads to greater myelination and faster overall signal transmission.

Effects of the APOEɛ4 Allele on the Relationship Between Tau and Amyloid-β in Early- and Late-Onset Alzheimer's Disease.

Little is known regarding the differential effects of the apolipoprotein E (APOE) ɛ4 on the regional topography of amyloid and tau in patients with both early-onset (EOAD) and late-onset Alzheimer's disease (LOAD). To compare the distribution and association of tau, amyloid, and cortical thickness among groups classified by the presence of APOEɛ4 allele and onset age. A total of 165 participants including 54 EOAD patients (29 ɛ4-; 25 ɛ4+), 45 LOAD patients (21 ɛ4-; 24 ɛ4+), and 66 age-matched controls underwent 3T MRI, 18F-THK5351 (THK) and 18F-flutemetamol (FLUTE) PET scans, APOE genotyping, and neuropsychological tests. Data for voxel-wise and standardized uptake values from PET scans were analyzed in the context of APOE and age at onset. EOAD ɛ4- patients showed greater THK retention in the association cortices, whereas their EOAD ɛ4+ counterparts had more retention in medial temporal areas. THK topography of LOAD ɛ4+ was similar to EOAD ɛ4 + . THK correlated positively with FLUTE and conversely with mean cortical thickness, being lowest in EOAD ɛ4-, highest in LOAD ɛ4-, and modest in ɛ4+ groups. Even in the APOEɛ4+ groups, THK tended to correlate with FLUTE and mean cortical thickness in the inferior parietal region in EOAD and in the medial temporal region in LOAD. LOAD ɛ4- manifested with prevalent small vessel disease markers and the lowest correlation between THK retention and cognition. Our observations suggest the differential effects of the APOEɛ4 on the relationship between tau and amyloid in EOAD and LOAD.

Amyloid accumulation in the medial temporal area starts in the mild cognitive impairment stage of Alzheimer’s disease in [18F]flutemetamol positron emission tomography

AbstractBackgroundThis study was aimed to evaluate the hierarchical accumulation of amyloid in the Alzheimer’s brain according to clinical stage using [18F]flutemetamol positron emission tomography.MethodThis was a prospective, single‐cohort study of volunteers who lived independently in Itabashi‐ku (Tokyo, Japan). One hundred thirty‐six participants (female/male = 96/40, mean age/standard deviation = 79.2/4.0 years) were recruited. Two subjects, one with meningeal thickening and another with sequelae in the brain, and 17 visually amyloid‐negative MCI subjects who possibly had neurodegenerative disease other than Alzheimer’s disease were excluded from the further analysis. We applied voxel‐based regression slope analysis using composite voxel of interest values calculated with Cortex ID Suite (GE Healthcare) and [18F]flutemetamol positron emission tomography images in three groups: 70 amyloid‐negative cognitively normal (CN) participants, 29 amyloid‐positive cognitively normal (PreC) participants, and 18 amyloid‐positive MCI (MCI+) participants. Statistical Parametric Mapping 12 software was used for analysis.ResultCompared with the CN group, the PreC group showed accelerated amyloid accumulation in a wide area, except for the medial temporal lobe, paracentral sulcus, and medial occipital lobe. In amyloid‐positive subjects, amyloid accumulation was quicker in the paracentral sulcus, occipital cortex, and left medial temporal lobe in the MCI+ group than in the PreC group. Additional voxel of interest analyses were applied to the statistically significant areas. In the right posterior cingulate area, there was no significant difference between the PreC and MCI+ groups; however, the PreC and MCI+ groups showed a significantly quicker amyloid accumulation than the CN group. In contrast, in the left medial temporal area, the increase of amyloid accumulation was greater only in the MCI+ group compared to the PreC and CN groups.ConclusionIn amyloid‐positive subjects, amyloid accumulation in the left medial temporal lobe did not increase in the preclinical stage. In the medial temporal and occipital lobes, which are relatively spared from amyloid accumulation, it is considered to start late in the MCI stage and not in the preclinical stage. Further study of volume and other biomarkers is requreid to evaluate the regional pathophysiological variability of AD.

Regional cerebral atrophy correlates with amyloid accumulation in preclinical Alzheimer’s disease

AbstractBackgroundThis study was aimed to evaluate the regional hierarchical brain atrophy among the preclinical to mild cognitive impairment (MCI) stages of Alzheimer’s disease associated with amyloid deposition using [18F]flutemetamol positron emission tomography and volumetric magnetic resonance imaging.MethodThis was a prospective, single‐cohort study of volunteers who were living independently in Itabashi‐ku (Tokyo, Japan). One hundred thirty‐six participants (female/male = 96/40, mean age/standard deviation = 79.2/4.0 years) were recruited. Two subjects, one with meningeal thickening and another with sequelae in the brain, and 17 visually amyloid‐negative MCI subjects who possibly had neurodegenerative disease other than Alzheimer’s disease were excluded from the further analysis. We applied voxel‐based regression slope analysis between composite voxel of interest values calculated with Cortex ID Suite (GE Healthcare) on [18F]flutemetamol positron emission tomography and volumetric magnetic resonance images in three groups: 70 amyloid‐negative cognitively normal (CN) participants, 29 amyloid‐positive cognitively normal (PreC) participants, and 18 amyloid‐positive MCI (MCI+) participants. Statistical Parametric Mapping 12 software was used for analysis.ResultEven in the cognitively normal stage, the PreC group showed a larger slope of atrophy in the basal forebrain and middle frontal gyri than the CN group. In the MCI+ group, the slopes were larger in the lateral and medial parietal lobes, uncus, and right lateral temporal areas.ConclusionThe speed of amyloid‐related atrophy in the basal forebrain and middle frontal gyri was quick even in the preclinical stage of Alzheimer’s disease. As no significant slope changes were observed among the three groups in the medial temporal area, except for the uncus, the well‐known medial temporal atrophy in early Alzheimer’s disease might not be related to the accumulation of amyloid.

APOEε4 genotype boosts neurodegenerative structural changes in medial temporal lobe areas in adults with Mild Cognitive Impairment

AbstractBackgroundApolipoprotein E ε4 allele (APOEε4) is considered the major genetic risk factor of Alzheimer´s Disease (AD). Structural magnetic resonance imaging (sMRI) studies demonstrated that, compared to APOEε4 non‐carriers, APOEε4 carriers display structural changes in lateral and medial temporal lobe (MTL). However, the knowledge about the impact of this genotype on hippocampal subfields is still limited. The present sMRI study aimed to evaluate volumetric and cortical thickness differences between adults with mild cognitive impairment (MCI) APOEε4 non‐carriers compared with MCI‐APOEε4 carriers.MethodTwelve MCI‐APOEε4 non‐carriers (mean age: 70.33 years, SD: 5.12) and ten MCI‐APOEε4 carriers (mean age: 72.70 years, SD: 6.38), diagnosed as MCI according Petersen criteria (Petersen, 2004; Albert et al., 2011), underwent neuropsychological assessment, cerebrospinal fluid, genetic and MRI examinations. MRI surface‐based morphometry analyses was conducted with the FreeSurfer software to evaluate volumetric and thickness differences in the hippocampal subfields and its surrounding MTL areas.ResultCompared with MCI‐APOEε4 non‐carriers, the MCI‐APOEε4 carriers group showed a significant reduced volume in several areas of the left hemisphere. Specifically, in this hemisphere volumetric changes were found in the entorhinal cortex, the whole hippocampus and in its head, body and tail; the head of presubiculum, the head and body of subiculum, the CA1, CA3, CA4 subfields, the granulate cell of the molecular layer of dentate gyrus and the molecular layer of the hippocampus. This group also displayed a significant reduced volume in the right body of CA3 subfield.ConclusionThese results suggest that, in MCI adults, the presence of the APOEε4 genotype may have an additional neuropathological impact on the structure of brain regions of the MTL with a critical functional role in episodic memory, the most affected neurocognitive system in Alzheimer’s disease (AD). Particularly, the left MTL would show higher vulnerability to neurodegenerative changes in the prodromal stage of AD.

Longitudinal Changes in Insulin Resistance, Cognition, and AD Biomarkers across the AD Continuum

AbstractBackgroundTo determine if 3‐year changes in serum insulin resistance (IR) were related to changes in brain volume and glucose uptake, cognition, and CSF biomarkers in cognitively unimpaired and impaired older adults.MethodAlzheimer’s Disease Neuroimaging Initiative data was downloaded for 275 aged adults (55‐89 years). Participants had longitudinal T1‐ and T2‐weighted volume scans, fluorodeoxyglucose (FDG) scans, CSF β‐amyloid (Aβ) and tau species, and cognitive performance over baseline and months 6, 12, 18, 24, and 36. Growth curve modeling in R regressed IR against these outcomes, by itself and with clinical diagnosis as a moderator. Cognitively unimpaired (CU) adults were used as a reference group to determine potential effects in pathological aging.ResultIn AD and/or Mild Cognitive Impairment progressors to AD (MCI‐P), higher IR over time was related to progressive atrophy in medial temporal frontoinsular areas. Similarly, decline was seen in global cognition and both memory and executive function. HOMA1‐IR associations were partially mediated by p‐tau‐181. Among clinical diagnosis groups, higher IR was significantly related to amyloid, p‐tau‐181, and total tau 181 among AD patients but not MCI or unimpaired groups.ConclusionThese findings suggest that in older adults who develop AD or had AD at baseline, higher IR over time is related to brain atrophy and consequent cognitive decline, perhaps as a function of amyloid or tau deposition.

Functional brain networks reorganization in the absence of medial temporal lobe structures: an example of neuroplasticity

AbstractBackgroundMedial temporal lobe structures are particularly vulnerable in age‐related neurodegenerative diseases. Here, we investigated the brain reorganization that allows maintaining relatively normal global cognitive functioning in patients with herpes simplex encephalitis (HSE) – an infectious neurological disease ‐ with marked focal atrophy most pronounced in the medial temporal lobes, particularly the hippocampus. Using rs‐fMRI we (i) characterized the patterns of functional network organization, and (ii) compared the intra‐/interhemispheric functional connectivity (FC) within each patient.MethodA total of nine HSE patients were included (see Table 1), four of them were affected mainly in the left (LH) and five in the right (RH) hemisphere. The rs‐fMRI data were acquired after a long‐term follow‐up (median 16 years) of the disease and were preprocessed using the AFNI software. For each patient, using different brain parcellations, we computed the intra‐ and inter‐FC strength for each hemisphere separately, yielding four measures of intra‐FC LH/RH and inter‐FC LH/RH . We grouped the subjects according to their lesion‐side and their performance (low, high) in a memory task.ResultWe observed, regardless of the lesion side, a highly variable pattern of disrupted FC in each patient. Left‐lesioned patients showed high intra‐FCLH/RH particularly in the precuneus/posterior cingulate (PPC) and the angular gyrus while right‐lesioned patients exhibited a high inter‐FCRH in the medial prefrontal cortex (MPFC) and PPC regions. Both left and right‐lesioned showed decreased intra‐FCLH/RH in ventral medial temporal areas, more pronounced in the left‐lesioned patients (Figure1). Right‐lesioned individuals who showed a pattern of inter‐FC within the right MPF and PPC performed consistently higher on the memory task (percentiles &gt; 50) (Figure2).ConclusionThe substantial HSE‐induced medial temporal lobe lesions induce a global network reorganization. However, the side of the lesion seems to determine a specific pattern of network reorganization that is associated with differential cognitive performance. Left‐lesioned patients exhibited high PPC intra‐ and inter‐FCLH/RH and low memory performance while the right‐lesioned exhibited a high inter‐FCRH on the PPC and MPFC and better memory performance. Left lesions may result in nonadaptive brain reorganizations, however, right lesions, when linked to prefrontal brain reorganizations, may result in cognitive benefits and therefore be adaptive.

Joint-embeddings reveal functional differences in default-mode network architecture between marmosets and humans

The default-mode network (DMN) is a distributed functional brain system integral for social and higher-order cognition in humans with implications in a myriad of neuropsychological disorders. In this study, we compared the functional architecture of the DMN between humans and marmosets to assess their similarities and differences using joint gradients. This approach permits simultaneous large-scale mapping of functional systems across the cortex of humans and marmosets, revealing evidence of putative homologies between them. In doing so, we find that the DMN architecture of the marmoset exhibits differences along its anterolateral-posterior axis. Specifically, the anterolateral node of the DMN (dorsolateral prefrontal cortex) displayed weak connections and inconsistent connection topographies as compared to its posterior DMN-nodes (posterior cingulate and posterior parietal cortices). We also present evidence that the marmoset medial prefrontal cortex and temporal lobe areas correspond to other macroscopical distributed functional systems that are not part of the DMN. Given the importance of the marmoset as a pre-clinical primate model for higher-order cognitive functioning and the DMN's relevance to cognition, our results suggest that the marmoset may lack the capacity to integrate neural information to subserve cortical dynamics that are necessary for supporting diverse cognitive demands.

Decoding human spontaneous spiking activity in medial temporal lobe from scalp EEG

Linking scalp electroencephalography (EEG) signals and spontaneous firing activity from deep nuclei in humans is not trivial. To examine this, we analyzed simultaneous recordings of scalp EEG and unit activity in deeply located sites recorded overnight from patients undergoing pre-surgical invasive monitoring. We focused on modeling the within-subject average unit activity of two medial temporal lobe areas: amygdala and hippocampus. Linear regression model correlates the units' average firing activity to spectral features extracted from the EEG during wakefulness or non-REM sleep. We show that changes in mean firing activity in both areas and states can be estimated from EEG (Pearson r>0.2, p≪0.001). Region specificity was shown with respect to other areas. Both short- and long-term fluctuations in firing rates contributed to the model accuracy. This demonstrates that scalp EEG frequency modulations can predict changes in neuronal firing rates, opening a new horizon for non-invasive neurological and psychiatric interventions.

Supramarginal Gyrus and Angular Gyrus Subcortical Connections: A Microanatomical and Tractographic Study for Neurosurgeons

Background and Objectives: This article aims to investigate the subcortical microanatomy of the supramarginal gyrus (SMG) and angular gyrus (AnG) using a microfiber dissection technique and diffusion tensor imaging (DTI)/fiber tractography (FT). The cortical and subcortical structures of this region are highly functional, and their lesions often present clinically. For this reason, the possibility of post-surgical deficits is high. We focused on the supramarginal gyrus and the angular gyrus and reviewed their anatomy from a topographic, functional and surgical point of view, and aimed to raise awareness especially for neurosurgeons. Methods: Four previously frozen, formalin-fixed human brains were examined under the operating microscope using the fiber dissection technique. Four hemispheres were dissected from medial to lateral under the surgical microscope. Brain magnetic resonance imaging (MRI) of 20 healthy adults was examined. Pre-central and post-central gyrus were preserved to achieve topographic dominance in dissections of brain specimens. Each stage was photographed. Tractographic brain magnetic resonance imaging of 10 healthy adults was examined radiologically. Focusing on the supramarginal and angular gyrus, the white matter fibers passing under this region and their intersection areas were examined. These two methods were compared anatomically from the lateral view and radiologically from the sagittal view. Results: SMG and AnG were determined in brain specimens. The pre-central and post-central gyrus were topographically preserved. The superior and medial temporal gyrus, and inferior and superior parietal areas were decorticated from lateral to medial. U fibers, superior longitudinal fasciculus II (SLF II), superior longitudinal fasciculus III (SLF III), arcuat fasciculus (AF) and middle longitudinal fasciculus (MdLF) fiber groups were shown and subcortical fiber structures belonging to these regions were visualized by the DTI/FT method. The subcortical fiber groups under the SMG and the AnG were observed anatomically and radiologically to have a dense and complex structure. Conclusions: Due to the importance of the subcortical connections of SMG and AnG on speech function, tumoral lesions and surgeries of this region are of particular importance. The anatomical architecture of the complex subcortical structure, which is located on the projection of the SMG and AnG areas, was shown with a DTI/FT examination under a topographic dominance, preserving the pre-central and post-central gyrus. In this study, the importance of the anatomical localization, connections and functions of the supramarginal and angular gyrus was examined. More anatomical and radiological studies are needed to better understand this region and its connections.