Papez Circuit Research Articles

Human anterior thalamic stimulation evoked cortical potentials align with intrinsic functional connectivity

Characterizing human thalamocortical network is fundamental for understanding a vast array of human behaviors since the thalamus plays a central role in cortico-subcortical communication. Over the past few decades, advances in functional magnetic resonance imaging have allowed for spatial mapping of intrinsic resting-state functional connectivity (RSFC) between both cortical regions and in cortico-subcortical networks. Despite these advances, identifying the electrophysiological basis of human thalamocortical network architecture remains challenging. By leveraging stereoelectroencephalography electrodes temporarily implanted into distributed cortical regions and the anterior nucleus of the thalamus (ANT) of 10 patients with refractory focal epilepsy, we tested whether ANT stimulation evoked cortical potentials align with RSFC from the stimulation site, derived from a normative functional connectome (n = 1000). Our study identifies spatial convergence of ANT stimulation evoked cortical potentials and normative RSFC. Other than connections to the Papez circuit, the ANT was found to be closely connected to several distinct higher-order association cortices, including the precuneus, angular gyrus, dorsal lateral prefrontal cortex, and anterior insula. Remarkably, we found that the spatial distribution and magnitude of cortical-evoked responses to single-pulse electrical stimulation of the ANT aligned with the spatial pattern and strength of normative RSFC of the stimulation site. The present study provides electrophysiological evidence that stimulation evoked electrical activity flows along intrinsic brain networks connected on a thalamocortical level.

Alteration in resting-state effective connectivity within the Papez circuit in Presbycusis.

Previous studies have suggested that the Papez circuit may be involved in the cognitive impairment observed after hearing loss in presbycusis patients, yet relatively little is known about the pattern of changes in effective connectivity within the circuit. The aim of this study was to investigate abnormal alterations in resting-state effective connectivity within the Papez circuit and their association with cognitive decline in presbycusis patients. The spectral dynamic causal modelling (spDCM) approach was used for resting-state effective connectivity analysis in 61 presbycusis patients and 52 healthy controls (HCs) within the Papez circuit. The hippocampus (HPC), mamillary body (MB), anterior thalamic nuclei (ATN), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), entorhinal cortex (ERC), subiculum (Sub) and parahippocampal gyrus (PHG) were selected as the regions of interest (ROIs). The fully connected model difference in effective connectivity between the two groups was assessed, and the correlation between effective connectivity alteration and cognitive scale was analysed. We found that presbycusis patients demonstrated decreased effective connectivity from MB, PCC, and Sub to ACC relative to HCs, whereas higher effective connectivity strength was shown from HPC to MB, from ATN to PHG and from PHG to Sub. The effective connectivity from PHG to Sub was significantly negatively correlated with the complex figure test (CFT)-delay score (rho = -0.259, p = 0.044). The results support and reinforce the role of abnormal effective connectivity within the Papez circuit in the pathophysiology of presbycusis-related cognitive impairment and reveal its potential as a novel imaging marker.

E.5 Large scale network changes immediately after Magnetic Resonance Imaging-Guided Laser Interstitial Thermal Therapy (MRgLITT) for hypothalamic hamartoma

Background: Hypothalamic hamartomas (HH) are a challenging cause of seizure in children, partly because the neural circuitry involved in ictogenesis is incompletely understood. We review our institutions’ use of magnetic resonance imaging-guided laser interstitial thermal therapy (MRgLITT) to treat hypothalamic hamartoma (HH) with resting-state fMRI performed immediately before and after ablation. Methods: Seed-based whole brain connectivity to thalamic regions of interest was performed immediately pre- and post- MRgLITT. Multivariable generalized linear models were used to correlate resting-state data with seizure outcomes. Results: Eight patients underwent MRgLITT treatments for HH, with a mean follow up of 29 months. Four patients (50%) were seizure free at 12 months and two (25%) had a significant improvement in seizure frequency. We identified reduced thalamocortical connectivity involving the anterior cingulate and posterior parietal regions, consistent with disconnection of the mammillothalamic tract and interruption of Papez circuit. Large-scale thalamocortical connectivity changes were driven by children who subsequently became seizure free. Conclusions: Disconnection of the mammillothalamic tract and interruption of thalamic circuitry in patients undergoing MRgLITT for HH appears to be associated with improved seizure outcomes. The ability to assess network changes immediately post- MRgLITT could enable operative adjustments to be made mid-procedure to optimize seizure outcome in real time.

Korsakoff's Syndrome and Alzheimer's Disease-Commonalities and Specificities of Volumetric Brain Alterations within Papez Circuit.

Background: Alzheimer's disease (AD) and Korsakoff's syndrome (KS) are two major neurocognitive disorders characterized by amnesia but AD is degenerative while KS is not. The objective is to compare regional volume deficits within the Papez circuit in AD and KS, considering AD progression. Methods: 18 KS patients, 40 AD patients (20 with Moderate AD (MAD) matched on global cognitive deficits with KS patients and 20 with Severe AD (SAD)), and 70 healthy controls underwent structural MRI. Volumes of the hippocampi, thalami, cingulate gyri, mammillary bodies (MB) and mammillothalamic tracts (MTT) were extracted. Results: For the cingulate gyri, and anterior thalamic nuclei, all patient groups were affected compared to controls but did not differ between each other. Smaller volumes were observed in all patient groups compared to controls in the mediodorsal thalamic nuclei and MB, but these regions were more severely damaged in KS than AD. MTT volumes were damaged in KS only. Hippocampi were affected in all patient groups but more severely in the SAD than in the KS and MAD. Conclusions: There are commonalities in the pattern of volume deficits in KS and AD within the Papez circuit with the anterior thalamic nuclei, cingulate cortex and hippocampus (in MAD only) being damaged to the same extent. The specificity of KS relies on the alteration of the MTT and the severity of the MB shrinkage. Further comparative studies including other imaging modalities and a neuropsychological assessment are required.

Teaching NeuroImages: Persistent anterograde amnesia due to sequential, bilateral vascular damage to the Papez circuit

A 62-year-old previously cognitively intact man presented to the emergency department with acute impairment of anterograde memory (ability to form new memories).1 Head CT did not show acute changes; however, amnesia persisted. MRI disclosed an acute infarct in the left posterior hippocampus and a nonacute lacunar stroke in the right anterior thalamus (figure). Memory testing showed severe deficits in verbal and visual memory, persisting after 2 months. Bilateral lesions located anywhere in the Papez circuit (hippocampal formations, mammillary bodies, anterior thalamic nuclei, cingulate and parahippocampal cortices, and their connections via fornix and mammillothalamic tracts) may be implicated in marked, persistent anterograde memory deficits.1,2 The hippocampus receives its blood supply from collateral branches of the posterior cerebral artery and the anterior choroidal artery.3 The anterior thalamus is supplied by the tuberothalamic artery.4

Computerized Cognitive Training Enhances Episodic Memory by Down-Modulating Posterior Cingulate-Precuneus Connectivity in Older Persons With Mild Cognitive Impairment: A Randomized Controlled Trial

The neural mechanisms underlying the beneficial effects of a computerized cognitive training (CCT) program for improving episodic memory in older persons with mild cognitive impairment (MCI) remain unclear. This study aimed to use both functional and structural brain changes to elucidate the treatment effects of CCT on enhancing episodic memory. Single-blinded, multicenter randomized controlled trial on 60 older adults with MCI in Fuzhou, China. Participants were randomly assigned to either an 8-week 24-hour CCT program or a health education program as the control. Clinical outcomes included changes in scores on the immediate and/or delayed recall subtests of the Chinese auditory verbal learning test (CAVLT) and rey complex figure test (CFT), and changes in gray matter volume and the functional connectivity of the posterior cingulate cortex (PCC) and hippocampus in the Papez circuit on magnetic resonance imaging. Significant group-by-time effects showed greater improvements in both immediate and delayed recall scores of CAVLT and delayed recall scores of Rey CFT in participants receiving the CCT program compared to those in the health education program. Among the CCT participants, seed-based analyses revealed decreases in functional connectivity of the PCC and hippocampus with neural substrates in the parietal and occipital regions. The decreased PCC and precuneus connectivity were found to mediate patients' improvements in immediate recall function. An 8-week CCT program was effective for improving episodic memory in older individuals with MCI. The decrease in connectivity originating from the PCC and hippocampus is suggestive of potential plastic changes in the Papez circuit, which could have alleviated the age-related compensatory mechanism. The findings of this study also shed light on expanding the content and extending the frequency and duration of the CCT program in future studies.

Nonlinear Theta-Gamma Coupling between the Anterior Thalamus and Hippocampus Increases as a Function of Running Speed.

The hippocampal theta rhythm strongly correlates to awake behavior leading to theories that it represents a cognitive state of the brain. As theta has been observed in other regions of the Papez circuit, it has been theorized that activity propagates in a reentrant manner. These observations complement the energy cascade hypothesis in which large-amplitude, slow-frequency oscillations reflect activity propagating across a large population of neurons. Higher frequency oscillations, such as gamma, are related to the speed with which inhibitory and excitatory neurons interact and distribute activity on the local level. The energy cascade hypothesis suggests that the larger anatomic loops, maintaining theta, drive the smaller loops. As hippocampal theta increases in power with running speed, so does the power and frequency of the gamma rhythm. If theta is propagated through the circuit, it stands to reason that the local field potential (LFP) recorded in other regions would be coupled to the hippocampal theta, with the coupling increasing with running speed. We explored this hypothesis using open-source simultaneous recorded data from the CA1 region of the hippocampus and the anterior dorsal and anterior ventral thalamus. Cross-regional theta coupling increased with running speed. Although the power of the gamma rhythm was lower in the anterior thalamus, there was an increase in the coupling of hippocampal theta to anterior thalamic gamma. Broadly, the data support models of how activity moves across the nervous system, suggesting that the brain uses large-scale volleys of activity to support higher cognitive processes.

ANTERIOR THALAMIC ISCHAEMIC STROKE SECONDARY TO CARDIOPULMONARY ARREST.

Ischaemic anterior thalamic lesions are rare and can present with disturbances of behaviour and memory. We describe a patient with post-cardiac arrest thalamic stroke. A 63-year-old man presented with cardiac arrest, was resuscitated after receiving life support, and showed no lesions on computed tomography. Three days later, he presented with short-term memory disturbance and disorientation, with a de novo anterior thalamic lesion. The anterior thalamic nucleus, supplied by the posterior communicating artery, is part of the Papez circuit and has a role in modulating behaviour and memory. An anterior thalamic syndrome presents with no sensory-motor deficits. Anterior thalamic stroke is a rare condition and can present with disturbances of short-term memory and behaviour; it usually does not include any motor or sensory deficits.Thalamic stroke can occur due to global hypoxia, such as during cardiopulmonary arrest.

Abnormal white matter integrity in Papez circuit in first-episode medication-naive adults with anxious depression: A combined voxel-based analysis and region of interest study

BackgroundAnxious depression is one of the subtypes of major depressive disorder (MDD), usually defined as “patients with MDD and high levels of anxiety symptoms”. Compared to non-anxious MDD (naMDD), patients with anxious MDD (aMDD) have more severe depressive symptoms and suicidal ideation, worse treatment outcomes and remission rates, and poorer prognosis. Current research suggests that the Papez circuit is an important brain structure closely related to emotion, memory, and cognition. This study applied DTI to explore the altered white matter integrity in Papez circuit of patients with aMDD. MethodsDTI data were acquired from 30 medication-naive outpatients with naMDD and 55 with aMDD and 88 demographically similar healthy control (HC) subjects. Voxel-based analysis (VBM) and region of interest (ROI) analysis were conducted to explore the significant difference of fractional anisotropy (FA) values among 3 groups. Pearson's correlations were performed to analyze the correlation between FA values and the score of HAMA-14 and HAMD-17. ResultsWe found that aMDD patients had significantly higher FA values in left fornix (belong to Papez circuit) and left posterior thalamic radiation and right anterior corona radiata (belong to limbic-thalamo-cortical circuitry) compared with HC. And there was variability in the white matter integrity in right posterior thalamic radiation (belong to limbic-thalamo-cortical circuitry) and left fornix (belong to Papez circuit) between aMDD and naMDD patients. LimitationsThe cross-sectional study and the population vary between aMDD group and naMDD group are limitations. ConclusionsAbnormal white matter integrity in Papez circuit and Limbic-Thalamo-Cortical circuitry may play an important role in the neuropathology of aMDD and might help to identify aMDD.

The APOE4 effect: structural brain differences in Alzheimer's disease according to the age at symptom onset.

How the APOE genotype can differentially affect cortical and subcortical memory structures in biomarker-confirmed early-onset (EOAD) and late-onset (LOAD) Alzheimer's disease (AD) was assessed. Eighty-seven cerebrospinal fluid (CSF) biomarker-confirmed AD patients were classified according to their APOE genotype and age at onset. 28 were EOAD APOE4 carriers (+EOAD), 21 EOAD APOE4 non-carriers (-EOAD), 23 LOAD APOE4 carriers (+LOAD) and 15 LOAD APOE4 non-carriers (-LOAD). Grey matter (GM) volume differences were analyzed using voxel-based morphometry in Papez circuit regions. Multiple regression analyses were performed to determine the relation between GM volume loss and cognition. Significantly more mammillary body atrophy in +EOAD compared to -EOAD is reported. The medial temporal and posterior cingulate cortex showed less GM in +LOAD compared to -LOAD. Medial temporal GM volume loss was also found in +EOAD compared to -LOAD. With an exception for +EOAD, medial temporal GM was strongly associated with episodic memory in the three groups, whilst posterior cingulate cortex GM volume was more related with visuospatial abilities. Visuospatial abilities and episodic memory were also associated with the anterior thalamic nucleus in -LOAD. Our results show that the APOE genotype has a significant effect on GM integrity as a function of age of disease onset. Specifically, whilst LOAD APOE4 genotype is mostly associated with increased medial temporal and parietal atrophy compared to -LOAD, for EOAD APOE4 might have a more specific effect on subcortical (mammillary body) structures. The findings suggest that APOE genotype needs to be taken into account when classifying patients by age at onset.

Optimal deep brain stimulation sites and networks for stimulation of the fornix in Alzheimer’s disease

Deep brain stimulation (DBS) to the fornix is an investigational treatment for patients with mild Alzheimer’s Disease. Outcomes from randomized clinical trials have shown that cognitive function improved in some patients but deteriorated in others. This could be explained by variance in electrode placement leading to differential engagement of neural circuits. To investigate this, we performed a post-hoc analysis on a multi-center cohort of 46 patients with DBS to the fornix (NCT00658125, NCT01608061). Using normative structural and functional connectivity data, we found that stimulation of the circuit of Papez and stria terminalis robustly associated with cognitive improvement (R = 0.53, p < 0.001). On a local level, the optimal stimulation site resided at the direct interface between these structures (R = 0.48, p < 0.001). Finally, modulating specific distributed brain networks related to memory accounted for optimal outcomes (R = 0.48, p < 0.001). Findings were robust to multiple cross-validation designs and may define an optimal network target that could refine DBS surgery and programming.

Subiculum fiber degeneration within the fornix white matter tract in 5xFAD mice

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disease that affects all components of the neurovascular unit. The hallmark pathology of AD, amyloid plaques and tau neurofibrillary tangles, aggregate within gray matter areas and spread across neural networks. Although AD pathology is scarce within white matter brain regions, white matter abnormalities have been observed in AD patients using diffusion tensor imaging (DTI; Sachdev et al 2013) and white matter tracts are putative therapeutic targets for deep brain stimulation (Lam et al 2020). Particularly, the fornix is a white matter tract which connects the hippocampus to brain regions of the classic Papez circuit and Default Mode Network (DMN). A recent whole brain analysis using transgenic 5xFAD/Thy1‐GFP mouse (Zhang et al 2020) found evidence of fornix degeneration and dystrophic axon terminals within the mammillary body (a major SUB target) occurring as early as 2 months of age. However, due to the broad expression of GFP under the Thy1 promotor, it is difficult to determine the origin of axon fibers and further characterize if other SUB pathways are also affected.MethodTo investigate white matter changes in AD and further characterize SUB axon degeneration, we performed triple anterograde tract‐tracing of SUB axon fibers and post‐mortem DTI tractography imaging within the same 8‐9 mo. old 5xFAD mice.ResultDTI imaging revealed a significant decrease in fiber density of the fornix white matter tract in 5xFAD mice. Quantification of tracer‐labeled fluorescent fiber density in the 5xFAD mice vs control mice also revealed significant degeneration of SUB fibers within the fornix white matter as well as downstream SUB targets including mammillary body, retrosplenial cortex, and anterior thalamus. Furthermore, SUB axon terminals in 5xFAD mice appeared dystrophic and terminal field topography was disrupted.ConclusionDTI imaging and anatomical tract tracing approaches reveal white matter degeneration in 5xFAD mice and the fornix/SUB fibers are particularly vulnerable in AD. Diminished SUB input to brain regions of the Papez circuit/DMN likely leads to neural network dysfunction. Whether amyloid pathology, neurovascular dysfunction, or inflammatory response in the 5xFAD mouse contributes to white matter degeneration remains to be determined by future studies.

Altered hippocampal functional connectivity after the rupture of anterior communicating artery aneurysm.

Aneurysmal subarachnoid hemorrhage (SAH) predisposes hippocampal injury, a major cause of follow-up cognitive impairment. Our previous study has revealed an abnormal resting-state brain network in patients after the rupture of anterior communicating artery (ACoA) aneurysm. However, the functional connectivity (FC) characteristics of the hippocampus and its relationship with cognitive performance in these patients remain unknown. This study ultimately included 26 patients and 19 age- and sex-matched controls who completed quality control for resting-state functional magnetic resonance imaging (fMRI). The mean time series for each side of the hippocampus was extracted from individuals and then a seed-to-voxel analysis was performed. We compared the difference in FC strength between the two groups and subsequently analyzed the correlations between abnormal FC and their cognitive performance. The results of bilateral hippocampus-based FC analysis were largely consistent. Compared with the healthy controls, patients after the rupture of ACoA aneurysm exhibited significantly decreased FC between the hippocampus and other brain structures within the Papez circuit, including bilateral anterior and middle cingulate cortex (MCC), bilateral medial superior frontal gyrus, and left inferior temporal gyrus (ITG). Instead, increased FC between the hippocampus and bilateral insula was observed. Correlation analyses showed that more subjective memory complaints or lower total cognitive scores were associated with decreased connectivity in the hippocampus and several brain regions such as left anterior cingulate cortex (ACC) and frontotemporal cortex. These results extend our previous findings and suggest that patients with ruptured ACoA aneurysm exist hypoconnectivity between the hippocampus and multiple brain regions within the Papez circuit. Deactivation of the Papez circuit may be a crucial neural mechanism related to cognitive deficits in patients after the rupture of ACoA aneurysm.

Structural and functional alterations within the Papez circuit in subacute stroke patients.

Beyond causing local injury, stroke disrupts structural and functional organization of the brain networks, exposing patients to a high risk of cognitive impairment by affecting the neural network activity. However, the impact of these pathological changes on cognition-related neural circuits is not well understood. In this study, we mainly focused on structures and directed functional connectivity within the Papez circuit in subacute stroke patients. Forty-five stroke patients and thirty-four age-, sex-matched healthy controls were included in our study. The Papez circuit gray matter were measured to explore ischemia-induced structural alterations. And Granger causality analysis with the hippocampus as seed regions was performed to identify alterations of directional functional connectivity within the neural circuit. We also explored the associations between cerebral changes with cognitive status. Compared with healthy controls, stroke patients revealed marked atrophy in gray matter of the Papez circuit, including ipsilateral hippocampus, amygdala, thalamus, and caudal anterior cingulate gyrus. Additionally, there are alterations in the directed functional connections between the bilateral hippocampus and cingulate gyrus within the Papez circuit. These altered effective connectivities were correlated with cognitive function after cerebrovascular event. Taken together, in the early post-stroke period, disruptions of the Papez circuit in both architecture and directed functional connectivity have already occurred and might affect the cognitive function. These findings have prompted researchers to better understand the potential mechanisms underlying vascular cognitive impairment and to investigate new therapeutic targets that could reduce cognitive burden.

Neuromodulation of the anterior thalamic nucleus as a therapeutic option for difficult-to-control epilepsy.

Deep brain stimulation (DBS) consists of the electrical stimulation of the subcortical structures by implanting electrodes connected to a pulse generator. The thalamus, being a structure that has multiple connections with various parts of the central nervous system, is a suitable target for DBS. The anterior thalamic nucleus (ANT) serves as an important relay site for the limbic system by receiving input from the hippocampus and mammillary bodies, and sending input to the cingulate gyrus; thus forming the Papez circuit. Due to these connections, the ANT constitutes an ideal route for the propagation of epileptogenic activity. ANT-DBS has excellent results in the control of complex partial seizures. The vast majority of patients with ANT-DBS have shown a significant reduction in the frequency of their seizures of more than 50%.

Long Term Performance of a Bi-Directional Neural Interface for Deep Brain Stimulation and Recording.

Background: In prior reports, we described the design and initial performance of a fully implantable, bi-directional neural interface system for use in deep brain and other neurostimulation applications. Here we provide an update on the chronic, long-term neural sensing performance of the system using traditional 4-contact leads and extend those results to include directional 8-contact leads.Methods: Seven ovine subjects were implanted with deep brain stimulation (DBS) leads at different nodes within the Circuit of Papez: four with unilateral leads in the anterior nucleus of the thalamus and hippocampus; two with bilateral fornix leads, and one with bilateral hippocampal leads. The leads were connected to either an Activa PC+S® (Medtronic) or Percept PC°ledR (Medtronic) deep brain stimulation and recording device. Spontaneous local field potentials (LFPs), evoked potentials (EPs), LFP response to stimulation, and electrode impedances were monitored chronically for periods of up to five years in these subjects.Results: The morphology, amplitude, and latencies of chronic hippocampal EPs evoked by thalamic stimulation remained stable over the duration of the study. Similarly, LFPs showed consistent spectral peaks with expected variation in absolute magnitude dependent upon behavioral state and other factors, but no systematic degradation of signal quality over time. Electrode impedances remained within expected ranges with little variation following an initial stabilization period. Coupled neural activity between the two nodes within the Papez circuit could be observed in synchronized recordings up to 5 years post-implant. The magnitude of passive LFP power recorded from directional electrode segments was indicative of the contacts that produced the greatest stimulation-induced changes in LFP power within the Papez network.Conclusion: The implanted device performed as designed, providing the ability to chronically stimulate and record neural activity within this network for up to 5 years of follow-up.

Korsakoff Syndrome: A Chronic Nutritional Deficiency Neuropsychiatric condition

In this review we have focused on Korsakoff syndrome, which is an aftermath of Wernicke encephalopathy (WE). Wernicke-Encephalopathy is neuropathologically marked by thiamine or vitamin B1 deficiency, typically induced by excessive alcohol use over an extended period of time in alcoholic patients, while in Nonalcoholic patients, it may be due to impaired utilization or accelerated usage of thiamine. Wernicke-Korsakoff syndrome (WKS) affects the brain region such as the mammillary bodies, periaqueductal and periventricular grey matter, colliculi bodies, and thalamus. The classic triads of WE are ophthalmoplegia, Nystagmus, and ataxia. The brain is examined using MRI and shows damage to the nuclei or memory transit- papez circuit that connects mamillary bodies to the anterior thalamus using the mammillothalamic tract responsible for the recollective memory in the diencephalon. Patients can be treated by parenteral thiamine administration and by abstinence of alcohol within their lifestyle. Keywords: Korsakoff Syndrome, alcoholic, non-alcoholic, Alzheimer's, memory-loss Wernicke encephalopathy, Wernicke-Korsakoff syndrome

Resting state effective connectivity abnormalities of the Papez circuit and cognitive performance in multiple sclerosis.

The Papez circuit is central to memory and emotional processes. However, little is known about its involvement in multiple sclerosis (MS). We aimed to investigate abnormalities of resting state (RS) effective connectivity (EC) between regions of the Papez circuit in MS and their relationship with cognitive performances. Sixty-two MS patients and 64 healthy controls (HC) underwent neuropsychological assessment, 3D T1-weighted, and RS functional MRI. RS EC analysis was performed using SPM12 and dynamic causal modeling. RS EC abnormalities were investigated using parametric empirical Bayes models and were correlated with cognitive scores. Compared to HC, MS patients showed (posterior probability > 0.95) higher EC between the right entorhinal cortex and right subiculum, and lower EC from the anterior cingulate cortex (ACC) to the posterior cingulate cortex (PCC), from left to right subiculum, from left anterior thalamus to ACC, and within ACC and PCC. Lower RS EC from the ACC to the PCC correlated with worse global cognitive scores (rho = 0.19; p = 0.03), worse visuospatial memory (rho = 0.19; p = 0.03) and worse semantic fluency (rho = 0.21; p = 0.02). Lower RS EC from the left to the right subiculum correlated with worse verbal memory (rho = 0.20; p = 0.02), lower RS EC within the ACC correlated with worse attention (rho = -0.19; p = 0.04) and more severe brain atrophy (rho = -0.26; p = 0.003). Higher EC from the right entorhinal cortex to right subiculum correlated with worse semantic fluency (rho = 0.21; p = 0.02). In conclusion, MS patients showed altered RS EC within the Papez circuit. Abnormal RS EC involving cingulate cortices and hippocampal formation contributed to explain cognitive deficits.

Resting State Effective Connectivity Abnormalities of the Papez Circuit Contribute to Explain Worse Cognitive Performances in Multiple Sclerosis Patients (P1-1.Virtual)

Resting State Effective Connectivity Abnormalities of the Papez Circuit Contribute to Explain Worse Cognitive Performances in Multiple Sclerosis Patients (P1-1.Virtual)

Propagation of Epileptiform Discharge along the Papez Circuit Demonstrated with Stereotactic EEG in a Patient with Temporal Lobe Epilepsy (P7-8.002)

Propagation of Epileptiform Discharge along the Papez Circuit Demonstrated with Stereotactic EEG in a Patient with Temporal Lobe Epilepsy (P7-8.002)