Papez proposed a network for higher brain function, which is termed the limbic network. However, the in vivo human limbic network has not been established. We investigated the connectivity of the human limbic system using corticocortical evoked potential (CCEP). This retrospective analysis included 28 patients with medically intractable focal epilepsy who underwent stereoelectroencephalography (SEEG) and CCEP. Alternating 1 Hz electrical stimuli were delivered to parts of the limbic system [anterior and posterior hippocampus, temporal pole, parahippocampal gyrus (PHG), amygdala, anterior (ACG) and posterior cingulate gyrus (PCG), medial and lateral orbitofrontal cortex (OF)]. A total of 40–60 stimuli were averaged in each trial to obtain CCEP responses. CCEP distributions were evaluated by calculating the root mean square (RMS) of CCEP responses. Anterior hippocampal stimulation elicited prominent CCEP responses in medial and lateral temporal structures, PCG, medial OF and insula over the ipsilateral hemisphere. Posterior hippocampal stimulation induced CCEP responses in the ipsilateral medial and lateral temporal structures and PCG. The findings also revealed connections from temporal pole to the ipsilateral medial temporal structures, and connections from PHG to the ipsilateral hippocampus and PCG. The amygdala projected to broad areas including the ipsilateral medial and lateral temporal structures, medial and lateral frontal areas, the cingulate gyrus, insula and inferior parietal lobule. ACG and PCG showed connections to the ipsilateral medial fronto-parietal areas and connections to bilateral medial temporo-parieto-occipital and lateral parieto-occipital areas, respectively. Medial and lateral OF stimulation induced responses in the adjacent cortices. This study revealed that various regions within the limbic network are intimately connected in reverberating circuits and are linked to specific ipsilateral and contralateral regions, which may reflect distinct functional roles.
Papez (1937) proposed a system involved in emotion and episodic memory, which is composed of the hypothalamus, hippocampus, mammillary body, thalamus, cingulate gyrus, parahippocampal gyrus (PHG) and the entorhinal cortex. Thereafter, Maclean, 1949 and Maclean, 1952 introduced the neurophysiological and neuroanatomical concept of “the limbic system”. He added the orbitofrontal cortex and amygdala, and named this group of structures the “limbic system”. These structures have interconnections constituting a harmonious mechanism which may elaborate the functions of emotion and memory. These previous reports contribute to understanding of the mechanisms of human higher function. Scoville and Milner (1957) described a profound and selective impairment in human memory after bilateral surgical removal of the medial temporal lobe. It has also been reported that medial temporal lobe damage causes memory impairment in cases of viral encephalitis (Damasio, Eslinger, Damasio, Van Hoesen, & Cornell, 1985), posterior cerebral artery occlusion (Benson, Marsden, & Meadows, 1974), and Alzheimer's disease (Hyman, Van Hoesen, Damasio & Barnes, 1984). These studies of human amnesia have identified the anatomical components of memory in the limbic network. However, despite these reports, little information is available regarding the connections within the limbic network; specifically the in-vivo anatomo-neurophysiological connectivity of the human limbic network has not been established. Understanding this network would be useful not only for understanding human higher brain functions, such as memory, recognition, and emotion, but also for elucidating the pathophysiology of neurological and psychiatric disorders, such as Alzheimer's disease and focal epilepsy involving various components of the limbic system, anxiety disorders and affective disorders. The investigations in limbic epilepsy can be misleading because the seizure onset is located in an anatomically deep region and the complicated spread pattern can give rise to atypical seizure semiologies and EEG findings ( Engel & Williamson, 2008). Therefore knowledge of the limbic network is important for the presurgical evaluation of patients with pharmacoresistant epilepsy arising within the limbic system.
