CA1 neurons in the human hippocampus are critical for autobiographical memory, mental time travel, and autonoetic consciousness

Abstract

Autobiographical memories in our lives are critically dependent on temporal lobe structures. However, the contribution of CA1 neurons in the human hippocampus to the retrieval of episodic autobiographical memory remains elusive. In patients with a rare acute transient global amnesia, highly focal lesions confined to the CA1 field of the hippocampus can be detected on MRI. We studied the effect of these lesions on autobiographical memory using a detailed autobiographical interview including the remember/know procedure. In 14 of 16 patients, focal lesions in the CA1 sector of the hippocampal cornu ammonis were detected. Autobiographical memory was significantly affected over all time periods, including memory for remote periods. Impairment of episodic memory and autonoetic consciousness exhibited a strong temporal gradient extending 30 to 40 y into the past. These results highlight the distinct and critical role of human hippocampal CA1 neurons in autobiographical memory retrieval and for re-experiencing detailed episodic memories.

Fig. 1.

Results on the (Left) overall autobiographical memory score, (Center) the strictly episodic score, and the (Right) remember-score over the time periods for patients in the acute episode (n = 16), during follow-up, and controls (n = 10). Mean ± SEM. Post hoc pair-wise comparisons (paired-samples t tests) between acute patients and follow-up per time period. *P < 0.05, **P < 0.01, ***P < 0.001.

Fig. 2.

Verbal and visuo-spatial memory results of the RAVLT and the Rey-Osterrieth complex figure of TGA patients (acute and follow-up) and controls (mean ± SD). P values from independent-samples t tests. P values from paired-samples t tests; **P < 0.01.

Fig. 3.

Three-dimensional model of the hippocampus showing the anterior-posterior distribution of hippocampal CA1 lesions. Lesions were located in the lateral hippocampus and were distributed along the anterior-posterior axis of the hippocampus. Green lesions indicate left lesions, red lesions show lesions in the right hippocampus, and blue shows two patients with bilateral lesions. Template modified after http://www9.biostr.washington.edu/da.html, used with permission, copyright 1997 University of Washington, USA.

Fig. 4.

(A) Anatomical template showing a representative coronary slice of the hippocampal cornu ammonis indicating sectors after Lorento de No. [Graphical template reproduced with permission from ref. (Copyright 2005, Springer-Verlag).] (B) Synopsis of all DWI/TR_2R lesions transferred to an anatomical template of the cornu ammonis. (C) MRI shows that lesions were confined to the CA1 area of the cornu ammonis.

Fig. 5.

Whole-brain 3T MRI of one patient showing a focal lesion in the head of the right hippocampus. The lesion in the diffusion-weighted imaging correlates with the lesion in T2-weighted sequences (red arrow). The lesion as seen in the diffusion-weighted image can be clearly differentiated from the hyperintense susceptibility artifacts at the skull base. Imaging in the coronal plane show that the lesion is confined to the CA1 sector of the cornu ammonis (Bottom, red arrow).