Local Functional Connectivity Research Articles

Homozygous Loss of Autism-Risk Gene CNTNAP2 Results in Reduced Local and Long-Range Prefrontal Functional Connectivity

Functional connectivity aberrancies, as measured with resting-state functional magnetic resonance imaging (rsfMRI), have been consistently observed in the brain of autism spectrum disorders (ASD) patients. However, the genetic and neurobiological underpinnings of these findings remain unclear. Homozygous mutations in contactin associated protein-like 2 (CNTNAP2), a neurexin-related cell-adhesion protein, are strongly linked to autism and epilepsy. Here we used rsfMRI to show that homozygous mice lacking Cntnap2 exhibit reduced long-range and local functional connectivity in prefrontal and midline brain "connectivity hubs." Long-range rsfMRI connectivity impairments affected heteromodal cortical regions and were prominent between fronto-posterior components of the mouse default-mode network, an effect that was associated with reduced social investigation, a core "autism trait" in mice. Notably, viral tracing revealed reduced frequency of prefrontal-projecting neural clusters in the cingulate cortex of Cntnap2-/- mutants, suggesting a possible contribution of defective mesoscale axonal wiring to the observed functional impairments. Macroscale cortico-cortical white-matter organization appeared to be otherwise preserved in these animals. These findings reveal a key contribution of ASD-associated gene CNTNAP2 in modulating macroscale functional connectivity, and suggest that homozygous loss-of-function mutations in this gene may predispose to neurodevelopmental disorders and autism through a selective dysregulation of connectivity in integrative prefrontal areas.

Hierarchical disruption in the Bayesian brain: Focal epilepsy and brain networks.

In this opinion paper, we describe a combined view of functional and effective brain connectivity along with the free-energy principle for investigating persistent disruptions in brain networks of patients with focal epilepsy. These changes are likely reflected in effective connectivity along the cortical hierarchy and construct the basis of increased local functional connectivity in focal epilepsy. We propose a testable framework based on dynamic causal modelling and functional connectivity analysis with the capacity of explaining commonly observed connectivity changes during interictal periods. We then hypothesise their possible relation with disrupted free-energy minimisation in the Bayesian brain. This may offer a new approach for neuroimaging to specifically develop and address hypotheses regarding the network pathomechanisms underlying epileptic phenotypes.

Effect of intermittent hypoxic training on hypoxia tolerance based on brain functional connectivity

The difference of brain functional connectivity between hypoxic and normal states was studied. The impact of intermittent hypoxic training on the hypoxia tolerance of the brain was explored. Multivariable empirical mode decomposition was applied to extract common inherent modes of multichannel EEG adaptively instead of a priori selection of filter bandwidth, and the first two scales of intrinsic mode functions expressed the differences in brain connectivity. To quantify synchronization and search for consistent performance, coherence, phase locking value and synchronization likelihood were all utilized. Brain networks extracted from these synchronization measures all displayed that both local and global functional connectivity declined with increasing time in a hypoxic state. Furthermore, early hypoxia of the brain was represented on brain connectivity before mental fatigue was detected by conventional neurobehavioral evaluation. The decrease of connectivity tended to slow down in hypoxic conditions after training, which indicated that hypoxia tolerance strengthened because of the hypoxic training.

Abnormal Profiles of Local Functional Connectivity Proximal to Focal Cortical Dysplasias.

IntroductionFocal cortical dysplasia (FCD) is a congenital malformation of cortical development that often leads to medically refractory epilepsy. Focal resection can be an effective treatment, but is challenging as the surgically relevant abnormality may exceed the MR-visible lesion. The aim of the current study is to develop methodology to characterize the profile of functional connectivity around FCDs using resting-state functional MRI and in the individual patient. The detection of aberrant connectivity may provide a means to more completely delineate the clinically relevant lesion.Materials and MethodsFifteen FCD patients (age, mean±SD: 31±11 years; 11 males) and 16 matched healthy controls (35±9 years; 7 males) underwent structural and functional imaging at 3 Tesla. The cortical surface was reconstructed from the T1-weighted scan and the registered functional MRI data was spatially normalized to a common anatomical standard space employing the gyral pattern. Seed-based functional connectivity was determined in all subjects for all dysplasia locations. A single patient was excluded based on an aberrant FCD seed time series. Functional connectivity as a function of geodesic distance (along the cortical surface) was compared between the individual patients and the homotopic normative connectivity profiles derived from the controls.ResultsIn 12/14 patients, aberrant profiles of functional connectivity were found, which demonstrated both hyper- and hypoconnectivity as well as combinations. Abnormal functional connectivity was typically found (also) beyond the lesion visible on structural MRI, while functional connectivity profiles not related to a lesion appeared normal in patients.ConclusionThis novel functional MRI technique has potential for delineating functionally aberrant from normal cortex beyond the structural lesion in FCD, which remains to be confirmed in future research.

Disrupted functional connectivity density in irritable bowel syndrome patients.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder resulting from a dysregulation of the brain-gut axis. However, its exact neural substrate still remains unclear. This study investigated the changes of intrinsic whole brain functional connectivity pattern in IBS using functional connectivity density (FCD). We acquired resting-state functional magnetic resonance imaging (rs-fMRI) data from thirty-two IBS patients and thirty-two healthy controls. Functional connectivity density, a data-driven algorithm, was used to compute the long-range and short-range FCD values for each voxel in the brain of each subject, implying the amount of distant and local functional connections of cortical hubs. The FCD maps were compared between IBS patients and healthy controls. Pearson correlations analysis was also performed between abnormal FCD values and clinical/psychometric scores in patients. Compared to healthy controls, IBS patients showed concurrently decreased long- and short-range FCD in bilateral anterior midcingulate cortices (aMCC) and inferior parietal lobules (IPL), and decreased long-range FCD in right anterior insula, and decreased short-range FCD in bilateral prefrontal cortices, subgenual anterior cingulate cortices and caudates. IBS patients also had concurrently increased long- and short-range FCD mainly in primary sensorimotor cortices, as well as increased long-range FCD in right supplementary motor area and increased short-range FCD in occipital lobe. In addition, some regions with altered FCD showed abnormal functional connectivity in brain regions involved in pain matrix of IBS patients. Furthermore, the abnormal FCD values in right anterior insula and left caudate showed significant correlation with severity of symptoms and disease duration of IBS patients respectively. In conclusion, patients with IBS have widely disrupted FCD, which decreased in brain regions involved in homeostatic afferent network, emotional arouse, and cognitive regulation, while increased in regions associated with sensorimotor modulation. And the observed functional connectivity alterations unveiled complicated working patterns of pain matrix in IBS patients. This study may provide us with new insight into the underlying brain network topology of IBS.

Cortico-Cortical Connections of Primary Sensory Areas and Associated Symptoms in Migraine.

Migraine is a recurring, episodic neurological disorder characterized by headache, nausea, vomiting, and sensory disturbances. These events are thought to arise from the activation and sensitization of neurons along the trigemino–vascular pathway. From animal studies, it is known that thalamocortical projections play an important role in the transmission of nociceptive signals from the meninges to the cortex. However, little is currently known about the potential involvement of cortico–cortical feedback projections from higher-order multisensory areas and/or feedforward projections from principle primary sensory areas or subcortical structures. In a large cohort of human migraine patients (N = 40) and matched healthy control subjects (N = 40), we used resting-state intrinsic functional connectivity to examine the cortical networks associated with the three main sensory perceptual modalities of vision, audition, and somatosensation. Specifically, we sought to explore the complexity of the sensory networks as they converge and become functionally coupled in multimodal systems. We also compared self-reported retrospective migraine symptoms in the same patients, examining the prevalence of sensory symptoms across the different phases of the migraine cycle. Our results show widespread and persistent disturbances in the perceptions of multiple sensory modalities. Consistent with this observation, we discovered that primary sensory areas maintain local functional connectivity but express impaired long-range connections to higher-order association areas (including regions of the default mode and salience network). We speculate that cortico–cortical interactions are necessary for the integration of information within and across the sensory modalities and, thus, could play an important role in the initiation of migraine and/or the development of its associated symptoms.

Optimized implementations of voxel-wise degree centrality and local functional connectivity density mapping in AFNI

Degree centrality (DC) and local functional connectivity density (lFCD) are statistics calculated from brain connectivity graphs that measure how important a brain region is to the graph. DC (a.k.a. global functional connectivity density) is calculated as the number of connections a region has with the rest of the brain (binary DC), or the sum of weights for those connections (weighted DC). lFCD was developed to be a surrogate measure of DC that is faster to calculate by restricting its computation to regions that are spatially adjacent. Although both of these measures are popular for investigating inter-individual variation in brain connectivity, efficient neuroimaging tools for computing them are scarce. The goal of this Brainhack project was to contribute optimized implementations of these algorithms to the widely used, open source, AFNI software package.

Functional MRI signal fluctuations highlight altered resting brain activity in Huntington's disease.

The fractional Amplitude of Low Frequency Fluctuations (fALFF) and the degree of local synchronization (Regional Homogeneity - ReHo) of resting-state BOLD signal have been suggested to map spontaneous neuronal activity and local functional connectivity, respectively. We compared voxelwise, independent of atrophy, the fALFF and ReHo patterns of 11 presymptomatic (ps-HD) and 28 symptomatic (sHD) Huntington's disease mutation carriers, with those of 40 normal volunteers, and tested their possible correlations with the motor and cognitive subscores of the Unified Huntington's Disease Rating Scale. In sHD patients, fALFF was mainly reduced bilaterally in parietal lobes (right precuneus being already affected in psHD), and in superior frontal gyri, and increased bilaterally in cerebellar lobules VI, VIII and IX, as well as in the right inferior temporal gyrus. In sHD, and to a lesser extent in psHD, ReHo was bilaterally reduced in putamina, cerebellar lobules III to VI, and superior medial frontal gyri, and increased in both psHD and sHD in fronto-basal cortices, and in the right temporal lobe. fALFF correlated inversely with cognitive scores in lobule IX of the cerebellum (mainly with total Stroop score, p<0.0001), and in the medial portions of both thalami. These results are consistent with a reduced neuronal activity in the cortical components of the executive networks, known to be affected in Huntington's Disease, and with reduced local functional integration in subcortical and cerebellar components of the sensori-motor network. Cerebellar clusters of significant correlation of fALFF with executive function scores may be related to compensatory mechanisms.

Post-traumatic stress influences local and remote functional connectivity: a resting-state functional magnetic resonance imaging study.

Post-traumatic stress disorder (PTSD) is associated with alterations in regional brain activation and remote functional connectivity (FC) in limbic and prefrontal cortex. However, little is known about local FC changes following a traumatic event. Resting-state functional magnetic resonance images were collected for typhoon survivors with (n=27) and without PTSD (n=33), and healthy controls (n=30). Local FC was examined by calculating regional homogeneity (ReHo), and remote FC was investigated between regions showing significant ReHo group differences. The PTSD group showed ReHo changes in multiple regions, including the amygdala, parahippocampal gyrus, and prefrontal cortex relative to both control groups. Compared with healthy controls, typhoon survivors had increased ReHo in the insula/inferior frontal gyrus, middle and dorsal anterior cingulate cortex (MCC/dACC), as well as enhanced negative FC between the MCC/dACC and posterior cingulate cortex (PCC)/precuneus. The typhoon-exposed control group exhibited higher ReHo in the PCC/precuneus than the PTSD and healthy control groups. Furthermore, positive correlations were found between PTSD symptom severity and ReHo in several regions. Post-traumatic stress can influence local and remote FC, irrespective of PTSD diagnosis. Future studies are needed to validate the findings and to determine whether the alterations represent pre-existing or acquired deficits.

Combining Optogenetics and Electrophysiology to Analyze Projection Neuron Circuits.

A set of methods is described for channelrhodopsin-2 (ChR2)-based synaptic circuit analysis that combines photostimulation of virally transfected presynaptic neurons' axons with whole-cell electrophysiological recordings from retrogradely labeled postsynaptic neurons. The approach exploits the preserved photoexcitability of ChR2-expressing axons in brain slices and can be used to assess either local or long-range functional connections. Stereotaxic injections are used both to express ChR2 selectively in presynaptic axons of interest (using rabies virus [RV] or adeno-associated virus [AAV]) and to label two types of postsynaptic projection neurons of interest with fluorescent retrograde tracers. In brain slices, tracer-labeled postsynaptic neurons are targeted for whole-cell electrophysiological recordings, and synaptic connections are assessed by sampling voltage or current responses to light-emitting diode (LED) photostimulation of ChR2-expressing axons. The data are analyzed to estimate the relative amplitude of synaptic input and other connectivity parameters. Pharmacological and electrophysiological manipulations extend the versatility of the basic approach, allowing the dissection of monosynaptic versus disynaptic responses, excitatory versus inhibitory responses, and more. The method enables rapid, quantitative characterization of synaptic connectivity between defined pre- and postsynaptic classes of neurons.

Temporal Evolution of Brain Functional Connectivity Metrics: Could 7 Min of Rest be Enough?

Unaccounted temporal dynamics of resting-state functional connectivity(FC) metrics challenges their potential as biomarkers for clinical applications in neuroscience. Here we studied the scan time required to reach stable values for various FC metrics including seed-voxel correlationsand spatial independent component analyses (sICA), and for the local functional connectivity density (lFCD), a graph theory metric. By increasing the number of time points included in the analysis, we assessed the effects of scan time on convergence of accuracy, sensitivity, specificity, reproducibility, and reliability of these FC metrics. The necessary scan time to attenuate the effects of the temporal dynamics by 80% varied across connectivity metrics and was shorter for lFCD (7 min) than for FC (11 min) or for sICA (10 min). Findings suggest that the scan time required to achieve stable FC is metric-dependent, with lFCD being the most resilient metric to the effects of temporal dynamics. Thus, the lFCD metric could be particularly useful for pediatric and patient populations who may not tolerate long scans.

Circulating androgens correlate with resting-state MRI in transgender men

Despite mounting evidence regarding the underlying neurobiology in transgender persons, information regarding resting-state activity, particularly after hormonal treatment, is lacking. The present study examined differences between transgender persons on long-term cross-sex hormone therapy and comparisons on two measures of local functional connectivity, intensity of spontaneous resting-state activity (low frequency fluctuations, LFF) and local synchronization of specific brain areas (regional homogeneity, ReHo). Nineteen transgender women (TW, male-to-female), 19 transgender men (TM, female-to-male), 21 non-transgender men (NTM) and 20 non-transgender women (NTW) underwent a resting-state MRI scan. The results showed differences between transgender persons and non-transgender comparisons on both LFF and ReHo measures in the frontal cortex, medial temporal lobe, and cerebellum. More interestingly, circulating androgens correlated for TM in the cerebellum and regions of the frontal cortex, an effect that was associated with treatment duration in the cerebellum. By comparison, no associations were found for TW with estrogens. These data provide first evidence for a potential masculinization of local functional connectivity in hormonally-treated transgender men.

A theoretical rut: revisiting and critically evaluating the generalized under/over-connectivity hypothesis of autism.

In 2004, two papers proposed that pervasive functional under-connectivity (Just etal., ) or a trade-off between excessive local connectivity at the cost of distal under-connectivity (Belmonte etal., ) characterizes atypical brain organization in autism. Here, we take stock of the most recent and rigorous functional and structural connectivity findings with a careful eye toward evaluating the extent to which they support these original hypotheses. Indeed, the empirical data do not support them. From rsfMRI studies in adolescents and adults, there is an emerging consensus regarding long-range functional connections indicating cortico-cortical under-connectivity, specifically involving the temporal lobes, combined with subcortical-cortical over-connectivity. In contrast, there is little to no consensus regarding local functional connectivity or findings from task-based functional connectivity studies. The structural connectivity data suggest that white matter tracts are pervasively weak, particularly in the temporal lobe. Together, these findings are revealing how deeply complex the story is regarding atypical neural network organization in autism. In other words, distance and strength of connectivity as individual factors or as interacting factors do not consistently explain the patterns of atypical neural connectivity in autism. Therefore, we make several methodological recommendations and highlight developmental considerations that will help researchers in the field cultivate new hypotheses about the nature and mechanisms of potentially aberrant functional and structural connectivity in autism.

Regional homogeneity changes in amnestic mild cognitive impairment patients

ObjectiveRegional Homogeneity (ReHo) measures the local coherence of spontaneous brain activity, and it is sensitive to detect aberrant local functional connectivity of brain region. We tried to explore the activity of brain network by ReHo method in amnestic mild cognitive impairment (aMCI) patients and examine the impact of regional brain atrophy on the functional results. MethodsData of both structural magnetic resonance images (MRI) and resting-state functional MRI scans were collected from 36 aMCI patients and 46 age-matched healthy controls. ResultsCompared with the HC subjects, the aMCI patients showed significant decreased ReHo areas in the right inferior parietal lobule (IPL), left posterior cingulate cortex/precuneus (PCC/PCu), left inferior temporal gyrus (ITG), right supramarginal gyrus (SMG), right fusiform gyrus (FG), bilateral lentiform nucleus (LN) and right cerebellum posterior lobe, with the right IPL being the most significant area. In addition, the aMCI group also had some significant increased ReHo areas in the right medial frontal gyrus (MFG), bilateral postcentral gyrus (PoCG), left cuneus and right lingual gyrus (LG), possibly reflective of some underlining compensatory mechanism. Furthermore, in the aMCI patients, we found the ReHo index of the left PCC was positively correlated with the AVLT-Immediate Recall scores, while the ReHo index of the left cuneus was negatively correlated with the MMSE scores. In addition, we found that after regressing out the identified regional brain atrophy, the significant correlations between fitted ReHo index and clinical variables still remained. ConclusionsOur study indicated that aMCI patients showed significant abnormal local coherence of biological activity in resting state and ReHo could serve as a sensitive biomarker in functional imaging studies of aMCI.

Characterizing dynamic local functional connectivity in the human brain.

Functional connectivity (FC), obtained from functional magnetic resonance imaging (fMRI), brings insights into the functional organization of the brain. Recently, rich and complex behaviour of brain has been revealed by the dynamic fluctuation of FC, which had previously been regarded as confounding ‘noise’. While the dynamics of long-distance, inter-regional FC has been extensively studied, the dynamics of local FC within a few millimetres in space remains largely unexplored. In this study, the local FC was depicted by regional homogeneity (ReHo), and the dynamics of local FC was obtained using sliding windows method. We observed a robust positive correlation between ReHo and its temporal variability, which was shown to be an intrinsic feature of the brain rather than a pure stochastic effect. Furthermore, fluctuation of ReHo was associated with global functional organization: (i) brain regions with higher centrality of inter-regional FC tended to possess higher ReHo variability; (ii) coherence of ReHo fluctuation was higher within brain’s functional modules. Finally, we observed alteration of ReHo variability during a motor task compared with resting-state. Our findings associated the temporal fluctuation of ReHo with brain function, opening up the possibility of dynamic local FC study in the future.

Temporal Changes in Local Functional Connectivity Density Reflect the Temporal Variability of the Amplitude of Low Frequency Fluctuations in Gray Matter.

Data-driven functional connectivity density (FCD) mapping is being increasingly utilized to assess brain connectomics at rest in the healthy brain and its disruption in neuropsychiatric diseases with the underlying assumption that the spatiotemporal hub distribution is stationary. However, recent studies show that functional connectivity is highly dynamic. Here we study the temporal variability of the local FCD (lFCD) at high spatiotemporal resolution (2-mm isotropic; 0.72s) using a sliding-window approach and ‘resting-state’ datasets from 40 healthy subjects collected under the Human Connectome Project. Prominent functional connectivity hubs in visual and posterior parietal cortices had pronounced temporal changes in local FCD. These dynamic patterns in the strength of the lFCD hubs occurred in cortical gray matter with high sensitivity (up to 85%) and specificity (> 85%) and showed high reproducibility (up to 72%) across sessions and high test-retest reliability (ICC(3,1) > 0.5). The temporal changes in lFCD predominantly occurred in medial occipitoparietal regions and were proportional to the strength of the connectivity hubs. The temporal variability of the lFCD was associated with the amplitude of the low frequency fluctuations (ALFF). Pure randomness did not account for the probability distribution of lFCD. Shannon entropy increased in proportion to the strength of the lFCD hubs suggesting high average flow of information per unit of time in the lFCD hubs, particularly in medial occipitoparietal regions. Thus, the higher dynamic range of the lFCD hubs is consistent with their role in the complex orchestration of interacting brain networks.

Diminished Quality of Life and Increased Brain Functional Connectivity in Patients with Hypothyroidism After Total Thyroidectomy.

Acute hypothyroidism induced by thyroid hormone withdrawal (THW) in patients with thyroid cancer after total thyroidectomy can affect mood and quality of life (QoL). While loss or dysregulation of thyroid hormone (TH) has these well-known behavioral consequences, the effects of TH alterations on brain function are not well understood. Resting state functional connectivity (FC) measured by functional magnetic resonance imaging (fMRI) allows non-invasive evaluation of human brain function. This study therefore examined whether THW affects resting state FC and whether changes in FC correlate with the mood or QoL of the patients with THW status. Twenty-one patients who had undergone total thyroidectomy for thyroid cancer were recruited. Resting state fMRI scanning of the brain, thyroid function tests, and administration of the 12-Item Short Form Health Survey (SF-12) and the Patient Health Questionnaire-9 (PHQ-9) were performed before and after two weeks of THW. Regional homogeneity (ReHo), one of the measures of resting state FC, was calculated, and each voxel was compared between before and after THW in 19 patients. The ReHo values were extracted from the regions of interest showing within-group differences in ReHo values after THW, and correlations of ReHo values with thyrotropin (TSH) levels, total score of the PHQ-9, and composite scores of the SF-12 were statistically evaluated. Higher ReHo was observed after THW in the brain cortical regions across primary motor and sensory, visual, and association cortices. Among the regions, the ReHo values in the bilateral pre- and postcentral gyri, bilateral middle occipito-temporal cortices, the left precuneus, and the left lingual gyrus showed positive correlations with serum TSH levels after THW. Higher ReHo values in the bilateral pre- and postcentral gyri, the left middle temporo-occipital cortices, and the left ligual gyrus correlated with the lower mental component summary score from the SF-12, while higher ReHo values in the bilateral pre- and postcentral gyri correlated with higher total scores in the PHQ-9. Local brain FC is increased in the acute hypothyroid state. Higher FC correlates with a poorer mental QoL and increased depression in the hypothyroid state.

EEG Resting State Functional Connectivity Analysis in Children with Benign Epilepsy with Centrotemporal Spikes.

In this study, we investigated changes in functional connectivity (FC) of the brain networks in patients with benign epilepsy with centrotemporal spikes (BECTS) compared to healthy controls using high-density EEG data collected under eyes-closed resting state condition. EEG source reconstruction was performed with exact Low Resolution Electromagnetic Tomography (eLORETA). We investigated FC between 84 Brodmann areas using lagged phase synchronization (LPS) in four frequency bands (δ, θ, α, and β). We further computed the network degree, clustering coefficient and efficiency. Compared to controls, patients displayed higher θ and α and lower β LPS values. In these frequency bands, patients were also characterized by less well ordered brain networks exhibiting higher global degrees and efficiencies and lower clustering coefficients. In the β band, patients exhibited reduced functional segregation and integration due to loss of both local and long-distance functional connections. These findings suggest that benign epileptic brain networks might be functionally disrupted due to their altered functional organization especially in the α and β frequency bands.

Functional Connectivity Hubs and Networks in the Awake Marmoset Brain.

In combination with advances in analytical methods, resting-state fMRI is allowing unprecedented access to a better understanding of the network organization of the brain. Increasing evidence suggests that this architecture may incorporate highly functionally connected nodes, or “hubs”, and we have recently proposed local functional connectivity density (lFCD) mapping to identify highly-connected nodes in the human brain. Here, we imaged awake nonhuman primates to test whether, like the human brain, the marmoset brain contains FC hubs. Ten adult common marmosets (Callithrix jacchus) were acclimated to mild, comfortable restraint using individualized helmets. Following restraint training, resting BOLD data were acquired during eight consecutive 10 min scans for each subject. lFCD revealed prominent cortical and subcortical hubs of connectivity across the marmoset brain; specifically, in primary and secondary visual cortices (V1/V2), higher-order visual association areas (A19M/V6[DM]), posterior parietal and posterior cingulate areas (PGM and A23b/A31), thalamus, dorsal and ventral striatal areas (caudate, putamen, lateral septal nucleus, and anterior cingulate cortex (A24a). lFCD hubs were highly connected to widespread areas of the brain, and further revealed significant network-network interactions. These data provide a baseline platform for future investigations in a nonhuman primate model of the brain’s network topology.

Increased Intrinsic Activity of Medial-Temporal Lobe Subregions is Associated with Decreased Cortical Thickness of Medial-Parietal Areas in Patients with Alzheimer's Disease Dementia.

In Alzheimer's disease (AD), disrupted connectivity between medial-parietal cortices and medial-temporal lobes (MTL) is linked with increased MTL local functional connectivity, and parietal atrophy is associated with increased MTL memory activation. We hypothesized that intrinsic activity in MTL subregions is increased and associated with medial-parietal degeneration and impaired memory in AD. To test this hypothesis, resting-state-functional and structural-MRI was assessed in 22 healthy controls, 22 mild cognitive impairment patients, and 21 AD-dementia patients. Intrinsic activity was measured by power-spectrum density of blood-oxygenation-level-dependent signal, medial-parietal degeneration by cortical thinning. In AD-dementia patients, intrinsic activity was increased for several right MTL subregions. Raised intrinsic activity in dentate gyrus and cornu ammonis 1 was associated with cortical thinning in posterior cingulate cortices, and at-trend with impaired delayed recall. Critically, increased intrinsic activity in the right entorhinal cortex was associated with ipsilateral posterior cingulate degeneration. Our results provide evidence that in AD, intrinsic activity in MTL subregions is increased and associated with medial-parietal atrophy. Results fit a model in which medial-parietal degeneration contributes to MTL dysconnectivity from medial-parietal cortices, potentially underpinning disinhibition-like changes in MTL activity.