H. M.'s medial temporal lobe lesion: findings from magnetic resonance imaging

Abstract

Although neuropsychological studies of the amnesic patient H. M. provide compelling evidence that normal memory function depends on the medial temporal lobe, the full extent of his surgical resection has not been elucidated. We conducted magnetic resonance imaging studies to specify precisely the extent of his bilateral resection and to document any other brain abnormalities. The MRI studies indicated that the lesion was bilaterally symmetrical and included the medial temporal polar cortex, most of the amygdaloid complex, most or all of the entorhinal cortex, and approximately half of the rostrocaudal extent of the intraventricular portion of the hippocampal formation (dentate gyrus, hippocampus, and subicular complex). The collateral sulcus was visible throughout much of the temporal lobe, indicating that portions of the ventral perirhinal cortex, located on the banks of the sulcus, were spared; the parahippocampal cortex (areas TF and TH) was largely intact. The rostrocaudal extent of the ablation was approximately 5.4 cm (left) and 5.1 cm (right). The caudal 2 cm, approximately, of the hippocampus body (normal length, approximately 4 cm) was intact, although atrophic. The temporal stem was intact. Outside the temporal lobes, the cerebellum demonstrated marked atrophy, and the mammillary nuclei were shrunken. The lateral temporal, frontal, parietal, and occipital lobe cortices appeared normal for age 66 years. The mediodorsal thalamic nuclei showed no obvious radiological changes. These findings reinforce the view that lesions of the hippocampal formation and adjacent cortical structures can produce global and enduring amnesia and can exacerbate amnesia beyond that seen after more selective hippocampal lesions.

Fig. 2.

T1-weighted series of coronal sections arranged from caudal (A) to rostral (P) to show the extent of the lesion in H. M. (see text for details). Scale bars (shown in L and P), 2 cm.

Fig. 2.

T1-weighted series of coronal sections arranged from caudal (A) to rostral (P) to show the extent of the lesion in H. M. (see text for details). Scale bars (shown in L and P), 2 cm.

Fig. 2.

T1-weighted series of coronal sections arranged from caudal (A) to rostral (P) to show the extent of the lesion in H. M. (see text for details). Scale bars (shown in L and P), 2 cm.

Fig. 1.

Left, Diagram showing the surgeon’s estimate of H. M.’s medial temporal lobe resection (Scoville and Milner, 1957, their Fig. 2, p 13). Theinset at the top is a ventral view of the human brain showing the predicted rostrocaudal extent of the ablation.A through D are drawings of coronal sections, arranged from rostral (A) to caudal (D), showing the predicted extent of the lesion. Note that although the lesion was made bilaterally, the right side is shown intact to illustrate structures that were removed.Right, An amended version of the original diagram indicating the extent of the ablation based on the MRI studies reported here. The rostrocaudal extent of the lesion is 5 cm rather than 8 cm, and the lesion does not extend as far laterally as initially pictured.

Fig. 4.

T2-weighted axial sections indicating the extent of the anterior temporal lobe resection bilaterally (bright signal areas in C–F). Cerebellar atrophy is obvious in A and B as increased fluid space (bright signal) surrounding the cerebellum and within folial spaces. Scale bar (shown in F), 2 cm.

Fig. 3.

T1-weighted parasagittal sections from the left (A) and right (B) sides of H. M.’s brain. The resected portion of the anterior temporal lobes is indicated bilaterally with an asterisk. The remaining portion of the intraventricular portion of the hippocampal formation is indicated with an open arrow. Scale bar (right ofA), 5 cm in 1 cm increments. Approximately 2 cm of preserved hippocampal formation is visible bilaterally. Note also the substantial cerebellar degeneration obvious as enlarged folial spaces.

Fig. 5.

This series of T1-weighted images is arranged from rostral (A) to caudal (F) through the temporal lobe of H. M. (shown on left) and of a 66-year-old man who has served as a control subject in neuropsychological studies. Sections from the control brain were selected to match as closely as possible the levels illustrated from H. M.’s brain. Images from H. M. are from the more recent three-dimensional acquisition in which 3.2 mm sections were reconstructed. The control brain illustrates the structures that are likely to have been eliminated in H. M.’s brain at each rostrocaudal level. A, The amygdala (A) and entorhinal cortex (EC) are heavily damaged at this level. The collateral sulcus (cs) is barely visible; therefore, little of the perirhinal cortex (PR) is likely to be intact at this level. B, This is the rostral level of the intraventricular portion of the hippocampal formation (H), which is missing bilaterally in H. M. The entorhinal cortex is also missing at this level. Because the collateral sulcus is visible, it is possible that some perirhinal cortex is intact at this level. The medial mammillary nucleus is present at this level and appears to be slightly shrunken in H. M.C, This is a rostral level through the body of the intraventricular hippocampal formation. Most of the hippocampal formation, including the entorhinal cortex, is missing at this level in H. M. D, A level through the caudal body of the hippocampus. Some tissue is visible bilaterally in the region of the hippocampus in H. M., although it is clearly shrunken compared with the normal control subject. This level is typically located caudal to the entorhinal cortex, which is replaced with parahippocampal cortex (areas TF and TH). E, This level is at the caudal pole of the hippocampus. There is no overt damage to the medial temporal lobe at this level. The intraventricular portion of the hippocampal formation does look shrunken, however, relative to the normal control subject. The fimbria (f) is visible in the normal control subject and in H. M. F, This level is caudal to the hippocampal formation and is presented primarily to illustrate the substantial atrophy of the cerebellum (Cer) in H. M. In the normal control subject, the cerebellar cortex extends to the limit provided by the tentorium cerebelli. In H. M., there is a substantial fluid-filled gap between the cerebellar cortex and the tentorium. Note throughout that H. M.’s cerebral cortex demonstrates relatively little sulcal widening and that sulcal widening is more pronounced in the cognitively normal control subject. Figure continues.

Fig. 5.

This series of T1-weighted images is arranged from rostral (A) to caudal (F) through the temporal lobe of H. M. (shown on left) and of a 66-year-old man who has served as a control subject in neuropsychological studies. Sections from the control brain were selected to match as closely as possible the levels illustrated from H. M.’s brain. Images from H. M. are from the more recent three-dimensional acquisition in which 3.2 mm sections were reconstructed. The control brain illustrates the structures that are likely to have been eliminated in H. M.’s brain at each rostrocaudal level. A, The amygdala (A) and entorhinal cortex (EC) are heavily damaged at this level. The collateral sulcus (cs) is barely visible; therefore, little of the perirhinal cortex (PR) is likely to be intact at this level. B, This is the rostral level of the intraventricular portion of the hippocampal formation (H), which is missing bilaterally in H. M. The entorhinal cortex is also missing at this level. Because the collateral sulcus is visible, it is possible that some perirhinal cortex is intact at this level. The medial mammillary nucleus is present at this level and appears to be slightly shrunken in H. M.C, This is a rostral level through the body of the intraventricular hippocampal formation. Most of the hippocampal formation, including the entorhinal cortex, is missing at this level in H. M. D, A level through the caudal body of the hippocampus. Some tissue is visible bilaterally in the region of the hippocampus in H. M., although it is clearly shrunken compared with the normal control subject. This level is typically located caudal to the entorhinal cortex, which is replaced with parahippocampal cortex (areas TF and TH). E, This level is at the caudal pole of the hippocampus. There is no overt damage to the medial temporal lobe at this level. The intraventricular portion of the hippocampal formation does look shrunken, however, relative to the normal control subject. The fimbria (f) is visible in the normal control subject and in H. M. F, This level is caudal to the hippocampal formation and is presented primarily to illustrate the substantial atrophy of the cerebellum (Cer) in H. M. In the normal control subject, the cerebellar cortex extends to the limit provided by the tentorium cerebelli. In H. M., there is a substantial fluid-filled gap between the cerebellar cortex and the tentorium. Note throughout that H. M.’s cerebral cortex demonstrates relatively little sulcal widening and that sulcal widening is more pronounced in the cognitively normal control subject. Figure continues.

Fig. 6.

Nissl-stained sections from a control brain and comparable MRI sections from H. M.’s scan at rostral (top) and caudal (bottom) levels through the hippocampal formation. H. M.’s left hemisphere is shown at the rostral level, and the right hemisphere is shown at the caudal level. The Nissl-stained sections provide information on the normal appearance of the removed (Rostral) portion of the hippocampal formation and the preserved (Caudal) portion. CS, Collateral sulcus; EC, entorhinal cortex; H, hippocampus; LGN, lateral geniculate nucleus; MMN, medial mammillary nucleus; PHG, parahippocampal gyrus; V, ventricle.