Understanding human episodic memory in aspects of large-scale brain networks has become one of the central themes in neuroscience over the last decade. Traditionally, episodic memory was regarded as mostly relying on medial temporal lobe (MTL) structures. However, recent studies have suggested involvement of more widely distributed cortical network and the importance of its interactive roles in the memory process. Both direct and indirect neuro-modulations of the memory network have been tried in experimental treatments of memory disorders. In this review, we focus on the functional organization of the MTL and other neocortical areas in episodic memory. Task-related neuroimaging studies together with lesion studies suggested that specific sub-regions of the MTL are responsible for specific components of memory. However, recent studies have emphasized that connectivity within MTL structures and even their network dynamics with other cortical areas are essential in the memory process. Resting-state functional network studies also have revealed that memory function is subserved by not only the MTL system but also a distributed network, particularly the default-mode network (DMN). Furthermore, researchers have begun to investigate memory networks throughout the entire brain not restricted to the specific resting-state network (RSN). Altered patterns of functional connectivity (FC) among distributed brain regions were observed in patients with memory impairments. Recently, studies have shown that brain stimulation may impact memory through modulating functional networks, carrying future implications of a novel interventional therapy for memory impairment.

SUMMARYObjective: Electrophysiologic hubs within the large-scale functional networks in mesial temporal lobe epilepsy (mTLE) with hippocampal sclerosis (HS) have not been investigated. We hypothesized that mTLE with HS has different resting-state network hubs in their large-scale functional networks compared to the hubs in healthy controls (HC). We also hypothesized that the hippocampus would be a functional hub in mTLE patients with HS. Methods: Resting-state functional networks, identified by using magnetoencephalography (MEG) signals in the theta, alpha, beta, and gamma frequency bands, were evaluated. Networks in 44 mTLE patients with HS (left mTLE = 22; right mTLE = 22) were compared with those in 46 age-matched HC. We investigated betweenness centrality at the source-level MEG network. Results: The main network hubs were at the pole of the left superior temporal gyrus in the beta band, the pole of the left middle temporal gyrus in the beta and gamma bands, left hippocampus in the theta and alpha bands, and right posterior cingulate gyrus in all four frequency bands in mTLE patients; all of which were different from the main network hubs in HC. Only patients with left mTLE showed profound differences from HC at the left hippocampus in the alpha band. Significance: Our analysis of resting-state MEG signals shows that altered electrophysiologic functional hubs in mTLE patients reflect pathophysiologic brain network reorganization. Because we detected network hubs in both hippocampal and extrahippocampal areas, it is probable that mTLE is a large-scale network disorder rather than a focal disorder. The hippocampus was a network hub in left mTLE but not in right mTLE patients, which may be due to intrinsic functional and structural asymmetries between left and right mTLE patients. The evaluation of cortical hubs, even in the spike-free resting-state, could be a clinical diagnostic marker of mTLE with HS.

It is not clear whether specific brain areas act as hubs in the eyes-closed (EC) resting state, which is an unconstrained state free from any passive or active tasks. Here, we used electrophysiological magnetoencephalography (MEG) signals to study functional cortical hubs in 88 participants. We identified several multispectral cortical hubs. Although cortical hubs vary slightly with different applied measures and frequency bands, the most consistent hubs were observed in the medial and posterior cingulate cortex, the left dorsolateral superior frontal cortex, and the left pole of the middle temporal cortex. Hubs were characterized as connector nodes integrating EC resting state functional networks. Hubs in the gamma band were more likely to include midline structures. Our results confirm the existence of multispectral cortical cores in EC resting state functional networks based on MEG and imply the existence of optimized functional networks in the resting brain.

A question to be addressed in the present study is how different the eyes-closed (EC) and eyes-open (EO) resting states are across frequency bands in terms of efficiency and centrality of the brain functional network. We investigated both the global and nodal efficiency and betweenness centrality in the EC and EO resting states from 39 volunteers. Mutual information was used to obtain the functional connectivity for each of the four frequency bands (theta, alpha, beta, and gamma). We showed that the cortical hubs with high betweenness centrality were maintained in the EC and EO resting states. We further showed that these hubs were associated with more than three frequency bands, suggesting that these hubs play an important role in the brain functional network at multiple temporal scales in the resting states. Enhanced global efficiency values were found in the theta and alpha bands in the EO state compared with those in the EC state. Moreover, it turned out that in the EO state the functional network was reorganized to enhance nodal efficiency at the nodes related to both the default mode and the dorsal attention networks and sensory-related resting-state networks. This result suggests that in the EO state the brain functional network was efficiently reorganized, facilitating the adaptation of the brain network to the change in state, which could help in understanding brain disorders that have a disturbance in communication with external environments by using the adaptation ability of brain functional networks.

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Background: Despite its potential to revolutionize the treatment of memory dysfunction, the efficacy of direct electrical hippocampal stimulation for memory performance has not yet been well characterized. One of the main challenges to cross-study comparison in this area of research is the diversity of the cognitive tasks used to measure memory performance. Objective: We hypothesized that the tasks that differentially engage the hippocampus may be differentially influenced by hippocampal stimulation and the behavioral effects would be related to the underlying hippocampal activity. Methods: To investigate this issue, we recorded intracranial EEG from and directly applied stimulation to the hippocampus of 10 epilepsy patients while they performed two different verbal memory tasks e a word pair associative memory task and a single item memory task. Results: Hippocampal stimulation modulated memory performance in a task-dependent manner, improving associative memory performance, while impairing item memory performance. In addition, subjects with poorer baseline cognitive function improved much more with stimulation. iEEG recordings from the hippocampus during non-stimulation encoding blocks revealed that the associative memory task elicited stronger theta oscillations than did item memory and that stronger theta power was related to memory performance. Conclusions: We show here for the first time that stimulation-induced associative memory enhancement was linked to increased theta power during retrieval. These results suggest that hippocampal stimulation enhances associative memory but not item memory because it engages more hippocampal theta activity and that, in general, increasing hippocampal theta may provide a neural mechanism for successful memory enhancement.

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OBJECTIVEMesial temporal lobe epilepsy (MTLE) surgery is associated with a risk of memory decline after surgery, but the effect of the extent and locus of temporal resection on postoperative memory function are controversial. The authors’ aim in this study was to confirm if selective resection is effective in preserving memory function and identify critical areas for specific memory decline after temporal resection.METHODSIn this single-center retrospective study, the authors investigated data from patients who underwent unilateral MTLE surgery between 2005 and 2015. Data from 74 MTLE patients (60.8% of whom were female; mean [SD] age at surgery 32 years [8.91 years] and duration of epilepsy 16 years [9.65 years]) with histologically proven hippocampal sclerosis were included. Forty-two patients underwent left-sided surgery. The resection area was manually delineated on each patient’s postoperative T1-weighted images. Mapping was performed to see if the resected group, compared with the nonresected group, had worse postoperative memory in various memory domains, including verbal item, verbal associative, and figural memory.RESULTSOverall, 95.9% had a favorable epilepsy outcome. In verbal item memory, resection of the left lateral temporal area was related to postoperative decline in immediate and delayed recall scores of word lists. In verbal associative memory, resection of the anterior part of the left hippocampus, left parahippocampal area, and left lateral temporal area was related to postoperative decline in immediate recall scores of word pairs. Resection of the posterior part of the left hippocampus, left parahippocampal area, and left lateral temporal area was related to delayed recall scores of the same task. Similarly, in the figural memory, postoperative decline of immediate recall scores was associated with the resection of the anterior part of the right hippocampus, amygdala, parahippocampal area, and superior temporal area, and decline of delayed recall scores was related to resection of the posterior part of the right hippocampus and parahippocampal area.CONCLUSIONSUsing voxel-based analysis, which accounts for the individual differences in the resection, the authors found a critical region for postoperative memory decline that is not revealed in the region-of-interest or groupwise comparison. Particularly, resection of the hippocampus was related to associative memory. In both verbal and visual memory, resection of the anterior part of the hippocampus was associated with immediate recall, and resection of the posterior part of the hippocampus was associated with delayed recall. Therefore, the authors’ results suggest that selective resection may be effective in preserving postoperative memory decline.