doi:10.1093/brain/awu303
Brain 2015: 138; 1–3
| e343
LETTER TO THE EDITOR Is there evidence of a subordinate role of the hippocampal CA1 field for declarative memory formation? Juri-Alexander Witt, Christoph Helmstaedter and Christian E. Elger Department of Epileptology, University of Bonn, Bonn, Germany Correspondence to: Dr Juri-Alexander Witt, Department of Epileptology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany E-mail: [email protected]
Sir, Neuropsychological investigations in patients with temporal lobe epilepsy (TLE) substantially contributed to our understanding of the neural underpinnings of human memory (Saling, 2009). Given the essential role of the hippocampus for episodic memory, epilepsy surgery for the treatment of pharmaco-resistant mesial TLE offers the unique possibility of relating the neuropathological status of the resected hippocampus to presurgical memory performance. With one exception (Zaidel et al., 1998), almost all respective studies found significant correlations between segmental neuronal cell loss within the left hippocampus and preoperative verbal memory functions (Sass et al., 1990, 1992, 1995; Baxendale et al., 1998; Zentner et al., 1999; Witt et al., 2014). One of these studies also reported significant correlations between cell counts of the right hippocampus and non-verbal memory (Zentner et al., 1999). Three additional studies found significant relationships between hippocampal cell loss and global memory performance of the isolated ipsilateral hemisphere during the Intracarotid Amobarbital Test (Sass et al., 1991; O’Rourke et al., 1993; Pauli et al., 2006). However, no clear picture emerged regarding the eventual superior role of specific subfields of the cornu ammonis (CA) or the dentate gyrus for episodic memory processes. Six of 10 relevant studies (60%) found significant correlations between presurgical memory performance and cell densities within the subfields CA3 and CA4, followed by CA1 (50%), dentate gyrus (40%) and CA2 (30%). Sample characteristics (often small, heterogeneous, and in some cases including both mesial and lateral TLE) and the use of different memory tests may well have contributed to this heterogeneity.
In a recent study of 104 patients with mesial TLE only, we analysed the role of segmental hippocampal cell loss and its underlying factor structure with regard to presurgical memory performance (Witt et al., 2014). In line with the medium-to-high intercorrelations between cell losses across hippocampal subfields (CA1–4 and internal and external limb of the dentate gyrus), principal component analysis indicated one single factor only which appeared to reflect the overall pathological status of the hippocampus. In-depth analyses revealed that the overall pathological status of the left hippocampus, rather than any specific subfield pathology, was relevant for verbal memory. Thus, the overall cell loss rather than cell loss within a specific subfield represents a marker for the structural and functional integrity of the hippocampus in mesial TLE. In their recent study published in Brain, Coras and colleagues (2014) took a different approach compared to the cited correlational studies; they investigated different cell loss patterns across hippocampal subfields and their impact on memory. The authors provided a comparison of the presurgical memory performance of patients with different subtypes of hippocampal sclerosis as differentiated by the first international consensus classification system of the International League Against Epilepsy (ILAE) (Blu¨mcke et al., 2013). The sample was comprised of 63 patients with hippocampal sclerosis ILAE Type 1 (which represents the most common type of hippocampal sclerosis with significant neuronal cell loss across all subfields, but with emphasis on CA1); 13 patients with hippocampal sclerosis ILAE Type 2 (CA1 predominant neuronal cell loss and gliosis whereas other sectors only show mild cell loss); six patients with hippocampal sclerosis ILAE Type 3 (CA4 predominant neuronal cell loss and gliosis
Advance Access publication October 28, 2014 ß The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: [email protected]
e343
| Brain 2015: 138; 1–3
whereas other subfields are only moderately affected); and 18 patients with no hippocampal sclerosis. The main result revealed that ‘patients with CA1 predominant cell loss (hippocampal sclerosis ILAE Type 2; n = 13) did not show declarative memory impairment and were indistinguishable from those patients without any hippocampal cell loss (n = 19)’. In this study, global memory performance during the Intracarotid Amobarbital Test and a verbal memory score from the Berliner Amnesie Test were the neuropsychological measures of interest. Focusing on the Intracarotid Amobarbital Test memory performance, ‘[r]egression and correlation analysis confirmed that decreased neuronal cell densities in CA1 did not contribute to the extent of memory impairment’. The authors conclude that ‘CA1 pyramidal cells are less critically involved in declarative human memory acquisition compared to dentate gyrus granule cells or CA4/CA3 pyramidal cells’. Referring to a study by Bartsch et al. (2011), it is argued that CA1 neurons are less related to anterograde memory than autobiographical or remote memory which, however, had not been assessed. Looking into the existing literature, such a subordinate or even negligible role of CA1 for anterograde declarative memory function is an unexpected and striking finding. This is because (i) there are case reports indicating that bilateral lesions limited to CA1 in humans lead to moderate-to-severe, predominantly anterograde amnesia, i.e. an impairment of declarative episodic memory formation (Zola-Morgan et al., 1986; Rempel-Clower et al., 1996); (ii) CA1 is known to be a relevant part of two major hippocampal circuits/pathways, the ‘trisynaptic circuit’ and the temporo-ammonic pathway, both associated with memory functions (Remondes and Schuman, 2004); and (iii) several studies have demonstrated significant correlations between neuronal cell densities of CA1 (and other subfields) and preoperative anterograde memory functions in patients with TLE (Sass et al., 1995; Baxendale et al., 1998; Zentner et al., 1999; Pauli et al., 2006; Witt et al., 2014). For example, Baxendale et al. (1998) found significant correlations between pre- and post-surgical verbal memory and neuronal cell densities of CA1 in patients with left TLE, while granule cell densities of the dentate gyrus were unrelated to memory function. Moreover, regarding the subfields of the cornu ammonis (CA1–4), another study from the Erlangen group (Pauli et al., 2006) reported the highest correlations between Intracarotid Amobarbital Test memory performance and neuronal cell densities within CA1 (r = 0.736, P 5 0.001). Finally, Rausch and Babb (1993) identified cell densities within CA1 as most representative for total cell loss across all subfields in a sample of patients who underwent epilepsy surgery for TLE. In that study, a higher CA1 cell loss was again associated with worse verbal memory performance in patients with left TLE. Apart from these more general considerations, a closer look into the presented data by Coras et al. (2014) additionally raises the question of whether the results might have been biased by the evaluation method. (i) The main findings and conclusions of this study are based on the neuropathological and neuropsychological results of a subgroup comprised solely of 13 patients with hippocampal sclerosis ILAE Type 2. Given the small sample size, the question of the degree of representativity and statistical power
Letter to the Editor arises. Moreover, only 5 of these 13 patients (38%) were resected on the language-dominant, presumably left side, and only these five were compared regarding verbal memory performance as assessed by the Berliner Amnesie Test: ‘Patients with left CA1 predominant sclerosis (HS ILAE Type 2) and left no hippocampal sclerosis had better preoperative verbal memory than patients with left HS ILAE Type 1 or left hippocampal sclerosis Type 3’.
In the majority of those patients with hippocampal sclerosis ILAE Type 2 the side of focus was in the non-dominant hemisphere [8/13 patients (62%)], therefore, one would not necessarily expect a presurgical deficit in verbal memory. As the authors used a total verbal memory score as the only measure of the Berliner Amnesie Test, the question remains as to whether nonverbal visuospatial memory deficits have been missed. (ii) Regarding the neuropsychological findings, only group data are reported and not the frequencies of individually impaired patients per subgroup. However, the authors present a figure in which 2 of 13 patients (15%) with hippocampal sclerosis ILAE Type 2 show below average/impaired Intracarotid Amobarbital Test memory performance, and two additional patients (15%) with hippocampal sclerosis ILAE Type 2 show borderline performance. At least some patients with hippocampal sclerosis ILAE Type 2 did indeed show mild memory deficits. Searching our own database, we identified six patients who underwent epilepsy surgery in Bonn for mesial TLE (three within the left, three within the right hemisphere) and whose hippocampal specimens had been classified as hippocampal sclerosis ILAE Type 2 at the Department of Neuropathology at the University Hospital of Erlangen. Using measures with proven sensitivity to mesiotemporal pathology (Helmstaedter et al., 1997; Gleissner et al., 1998; Zentner et al., 1999), the presurgical assessment of verbal and figural learning and memory (VLMT + DCSR) indicated impaired performance in all six patients in at least one of the key memory parameters (Table 1). A higher sensitivity/ clinical validity of these measures regarding temporomesial (dys)function might explain this divergent finding. Different verbal memory tests may have different sensitivities to left hippocampal function depending on the specific cognitive architecture of the employed test as pointed out by Saling (2009). In this regard, we are not aware of studies on the validity of the Berliner Amnesie Test and its total verbal memory score, which was used in the study by Coras et al. (2014) as a verbal memory measure. In light of our raised concerns and our own data presented, we suggest a more cautious interpretation and generalization of the findings by Coras et al. (2014). Nonetheless, it is important to highlight that the clinical and neuropsychological characterization of neuropathological subtypes is an important and necessary approach in establishing the validity and relevance of newly proposed classification systems. In the case of hippocampal sclerosis, the low number of ‘atypical’ subtypes (such as hippocampal sclerosis ILAE Types 2 or 3) calls for multicentric studies supervised by investigators with excellent neuropathological expertise, such as Roland Coras and Ingmar Blu¨mcke from the University Hospital of Erlangen.
Letter to the Editor
Brain 2015: 138; 1–3
| e343
Table 1 Age-corrected presurgical memory performance of patients with hippocampal sclerosis ILAE Type 2 (standard values) Patients with HS ILAE Type 2
Side of surgery
Presurgical verbal memory (VLMT)
Presurgical figural memory (DCS-R)
Learning
Delayed free recall
Loss over time
Recognition
Learning
Recognition
1 2 3 4 5 6
Left Left Left Right Right Right
107 97 81 109 80 95
93 91 66 103 91 99
81 88 77 94 104 97
97 44 79 100 105 104
78 84 84 77 53 68
79 90 84 96 44 61
Impairments (i.e. performance of 41 standard deviation below the mean of the normative sample) are highlighted in bold. HS = hippocampal sclerosis; VLMT = Verbaler Lern- und Merkfa¨higkeitstest; DCS-R = Diagnosticum fu¨r Cerebralscha¨digung – revised.
References Bartsch T, Dohring J, Rohr A, Jansen O, Deuschl G. CA1 neurons in the human hippocampus are critical for autobiographical memory, mental time travel, and autonoetic consciousness. Proc Natl Acad Sci USA 2011; 108: 17562–7. Baxendale SA, Van Paesschen W, Thompson PJ, Duncan JS, Harkness WF, Shorvon SD. Hippocampal cell loss and gliosis: relationship to preoperative and postoperative memory function. Neuropsychiatry Neuropsychol Behav Neurol 1998; 11: 12–21. Blu¨mcke I, Thom M, Aronica E, Armstrong DD, Bartolomei F, Bernasconi A, et al. International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: a task force report from the ILAE commission on diagnostic methods. Epilepsia 2013; 54: 1315–29. Coras R, Pauli E, Li J, Schwarz M, Ro¨ssler K, Buchfelder M, et al. Differential influence of hippocampal subfields to memory formation: insights from TLE patients. Brain 2014; 137: 1945–57. Gleissner U, Helmstaedter C, Elger CE. Right hippocampal contribution to visual memory: a presurgical and postsurgical study in patients with temporal lobe epilepsy. J Neurol Neurosurg Psychiatry 1998; 65: 665–9. Helmstaedter C, Grunwald T, Lehnertz K, Gleissner U, Elger CE. Differential involvement of left temporolateral and temporomesial structures in verbal declarative learning and memory: evidence from temporal lobe epilepsy. Brain Cogn 1997; 35: 110–31. O’Rourke DM, Saykin AJ, Gilhool JJ, Harley R, O’Connor MJ, Sperling MR. Unilateral hemispheric memory and hippocampal neuronal density in temporal lobe epilepsy. Neurosurgery 1993; 32: 574–81. Pauli E, Hildebrandt M, Romstock J, Stefan H, Blu¨mcke I. Deficient memory acquisition in temporal lobe epilepsy is predicted by hippocampal granule cell loss. Neurology 2006; 67: 1383–9. Rausch R, Babb TL. Hippocampal neuron loss and memory scores before and after temporal lobe surgery for epilepsy. Arch Neurol 1993; 50: 812–7.
Remondes M, Schuman EM. Role for a cortical input to hippocampal area CA1 in the consolidation of a long-term memory. Nature 2004; 431: 699–703. Rempel-Clower NL, Zola SM, Squire LR, Amaral DG. Three cases of enduring memory impairment after bilateral damage limited to the hippocampal formation. J Neurosci 1996; 16: 5233–55. Saling MM. Verbal memory in mesial temporal lobe epilepsy: beyond material specificity. Brain 2009; 132: 570–82. Sass KJ, Buchanan CP, Kraemer S, Westerveld M, Kim JH, Spencer DD. Verbal memory impairment resulting from hippocampal neuron loss among epileptic patients with structural lesions. Neurology 1995; 45: 2154–8. Sass KJ, Lencz T, Westerveld M, Novelly RA, Spencer DD, Kim JH. The neural substrate of memory impairment demonstrated by the intracarotid amobarbital procedure. Arch Neurol 1991; 48: 48–52. Sass KJ, Sass A, Westerveld M, Lencz T, Novelly RA, Kim JH, et al. Specificity in the correlation of verbal memory and hippocampal neuron loss: dissociation of memory, language, and verbal intellectual ability. J Clin Exp Neuropsychol 1992; 14: 662–72. Sass KJ, Spencer DD, Kim JH, Westerveld M, Novelly RA, Lencz T. Verbal memory impairment correlates with hippocampal pyramidal cell density. Neurology 1990; 40: 1694–7. Witt JA, Coras R, Schramm J, Becker AJ, Elger CE, Blu¨mcke I, et al. The overall pathological status of the left hippocampus determines preoperative verbal memory performance in left mesial temporal lobe epilepsy. Hippocampus 2014; 24: 446–54. Zaidel DW, Esiri MM, Beardsworth ED. Observations on the relationship between verbal explicit and implicit memory and density of neurons in the hippocampus. Neuropsychologia 1998; 36: 1049–62. Zentner J, Wolf HK, Helmstaedter C, Grunwald T, Aliashkevich AF, Wiestler OD, et al. Clinical relevance of amygdala sclerosis in temporal lobe epilepsy. J Neurosurg 1999; 91: 59–67. Zola-Morgan S, Squire LR, Amaral DG. Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus. J Neurosci 1986; 6: 2950–67.
Copyright of Brain: A Journal of Neurology is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Brain 2015: 138; 1–3
| e343
LETTER TO THE EDITOR Is there evidence of a subordinate role of the hippocampal CA1 field for declarative memory formation? Juri-Alexander Witt, Christoph Helmstaedter and Christian E. Elger Department of Epileptology, University of Bonn, Bonn, Germany Correspondence to: Dr Juri-Alexander Witt, Department of Epileptology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany E-mail: [email protected]
Sir, Neuropsychological investigations in patients with temporal lobe epilepsy (TLE) substantially contributed to our understanding of the neural underpinnings of human memory (Saling, 2009). Given the essential role of the hippocampus for episodic memory, epilepsy surgery for the treatment of pharmaco-resistant mesial TLE offers the unique possibility of relating the neuropathological status of the resected hippocampus to presurgical memory performance. With one exception (Zaidel et al., 1998), almost all respective studies found significant correlations between segmental neuronal cell loss within the left hippocampus and preoperative verbal memory functions (Sass et al., 1990, 1992, 1995; Baxendale et al., 1998; Zentner et al., 1999; Witt et al., 2014). One of these studies also reported significant correlations between cell counts of the right hippocampus and non-verbal memory (Zentner et al., 1999). Three additional studies found significant relationships between hippocampal cell loss and global memory performance of the isolated ipsilateral hemisphere during the Intracarotid Amobarbital Test (Sass et al., 1991; O’Rourke et al., 1993; Pauli et al., 2006). However, no clear picture emerged regarding the eventual superior role of specific subfields of the cornu ammonis (CA) or the dentate gyrus for episodic memory processes. Six of 10 relevant studies (60%) found significant correlations between presurgical memory performance and cell densities within the subfields CA3 and CA4, followed by CA1 (50%), dentate gyrus (40%) and CA2 (30%). Sample characteristics (often small, heterogeneous, and in some cases including both mesial and lateral TLE) and the use of different memory tests may well have contributed to this heterogeneity.
In a recent study of 104 patients with mesial TLE only, we analysed the role of segmental hippocampal cell loss and its underlying factor structure with regard to presurgical memory performance (Witt et al., 2014). In line with the medium-to-high intercorrelations between cell losses across hippocampal subfields (CA1–4 and internal and external limb of the dentate gyrus), principal component analysis indicated one single factor only which appeared to reflect the overall pathological status of the hippocampus. In-depth analyses revealed that the overall pathological status of the left hippocampus, rather than any specific subfield pathology, was relevant for verbal memory. Thus, the overall cell loss rather than cell loss within a specific subfield represents a marker for the structural and functional integrity of the hippocampus in mesial TLE. In their recent study published in Brain, Coras and colleagues (2014) took a different approach compared to the cited correlational studies; they investigated different cell loss patterns across hippocampal subfields and their impact on memory. The authors provided a comparison of the presurgical memory performance of patients with different subtypes of hippocampal sclerosis as differentiated by the first international consensus classification system of the International League Against Epilepsy (ILAE) (Blu¨mcke et al., 2013). The sample was comprised of 63 patients with hippocampal sclerosis ILAE Type 1 (which represents the most common type of hippocampal sclerosis with significant neuronal cell loss across all subfields, but with emphasis on CA1); 13 patients with hippocampal sclerosis ILAE Type 2 (CA1 predominant neuronal cell loss and gliosis whereas other sectors only show mild cell loss); six patients with hippocampal sclerosis ILAE Type 3 (CA4 predominant neuronal cell loss and gliosis
Advance Access publication October 28, 2014 ß The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: [email protected]
e343
| Brain 2015: 138; 1–3
whereas other subfields are only moderately affected); and 18 patients with no hippocampal sclerosis. The main result revealed that ‘patients with CA1 predominant cell loss (hippocampal sclerosis ILAE Type 2; n = 13) did not show declarative memory impairment and were indistinguishable from those patients without any hippocampal cell loss (n = 19)’. In this study, global memory performance during the Intracarotid Amobarbital Test and a verbal memory score from the Berliner Amnesie Test were the neuropsychological measures of interest. Focusing on the Intracarotid Amobarbital Test memory performance, ‘[r]egression and correlation analysis confirmed that decreased neuronal cell densities in CA1 did not contribute to the extent of memory impairment’. The authors conclude that ‘CA1 pyramidal cells are less critically involved in declarative human memory acquisition compared to dentate gyrus granule cells or CA4/CA3 pyramidal cells’. Referring to a study by Bartsch et al. (2011), it is argued that CA1 neurons are less related to anterograde memory than autobiographical or remote memory which, however, had not been assessed. Looking into the existing literature, such a subordinate or even negligible role of CA1 for anterograde declarative memory function is an unexpected and striking finding. This is because (i) there are case reports indicating that bilateral lesions limited to CA1 in humans lead to moderate-to-severe, predominantly anterograde amnesia, i.e. an impairment of declarative episodic memory formation (Zola-Morgan et al., 1986; Rempel-Clower et al., 1996); (ii) CA1 is known to be a relevant part of two major hippocampal circuits/pathways, the ‘trisynaptic circuit’ and the temporo-ammonic pathway, both associated with memory functions (Remondes and Schuman, 2004); and (iii) several studies have demonstrated significant correlations between neuronal cell densities of CA1 (and other subfields) and preoperative anterograde memory functions in patients with TLE (Sass et al., 1995; Baxendale et al., 1998; Zentner et al., 1999; Pauli et al., 2006; Witt et al., 2014). For example, Baxendale et al. (1998) found significant correlations between pre- and post-surgical verbal memory and neuronal cell densities of CA1 in patients with left TLE, while granule cell densities of the dentate gyrus were unrelated to memory function. Moreover, regarding the subfields of the cornu ammonis (CA1–4), another study from the Erlangen group (Pauli et al., 2006) reported the highest correlations between Intracarotid Amobarbital Test memory performance and neuronal cell densities within CA1 (r = 0.736, P 5 0.001). Finally, Rausch and Babb (1993) identified cell densities within CA1 as most representative for total cell loss across all subfields in a sample of patients who underwent epilepsy surgery for TLE. In that study, a higher CA1 cell loss was again associated with worse verbal memory performance in patients with left TLE. Apart from these more general considerations, a closer look into the presented data by Coras et al. (2014) additionally raises the question of whether the results might have been biased by the evaluation method. (i) The main findings and conclusions of this study are based on the neuropathological and neuropsychological results of a subgroup comprised solely of 13 patients with hippocampal sclerosis ILAE Type 2. Given the small sample size, the question of the degree of representativity and statistical power
Letter to the Editor arises. Moreover, only 5 of these 13 patients (38%) were resected on the language-dominant, presumably left side, and only these five were compared regarding verbal memory performance as assessed by the Berliner Amnesie Test: ‘Patients with left CA1 predominant sclerosis (HS ILAE Type 2) and left no hippocampal sclerosis had better preoperative verbal memory than patients with left HS ILAE Type 1 or left hippocampal sclerosis Type 3’.
In the majority of those patients with hippocampal sclerosis ILAE Type 2 the side of focus was in the non-dominant hemisphere [8/13 patients (62%)], therefore, one would not necessarily expect a presurgical deficit in verbal memory. As the authors used a total verbal memory score as the only measure of the Berliner Amnesie Test, the question remains as to whether nonverbal visuospatial memory deficits have been missed. (ii) Regarding the neuropsychological findings, only group data are reported and not the frequencies of individually impaired patients per subgroup. However, the authors present a figure in which 2 of 13 patients (15%) with hippocampal sclerosis ILAE Type 2 show below average/impaired Intracarotid Amobarbital Test memory performance, and two additional patients (15%) with hippocampal sclerosis ILAE Type 2 show borderline performance. At least some patients with hippocampal sclerosis ILAE Type 2 did indeed show mild memory deficits. Searching our own database, we identified six patients who underwent epilepsy surgery in Bonn for mesial TLE (three within the left, three within the right hemisphere) and whose hippocampal specimens had been classified as hippocampal sclerosis ILAE Type 2 at the Department of Neuropathology at the University Hospital of Erlangen. Using measures with proven sensitivity to mesiotemporal pathology (Helmstaedter et al., 1997; Gleissner et al., 1998; Zentner et al., 1999), the presurgical assessment of verbal and figural learning and memory (VLMT + DCSR) indicated impaired performance in all six patients in at least one of the key memory parameters (Table 1). A higher sensitivity/ clinical validity of these measures regarding temporomesial (dys)function might explain this divergent finding. Different verbal memory tests may have different sensitivities to left hippocampal function depending on the specific cognitive architecture of the employed test as pointed out by Saling (2009). In this regard, we are not aware of studies on the validity of the Berliner Amnesie Test and its total verbal memory score, which was used in the study by Coras et al. (2014) as a verbal memory measure. In light of our raised concerns and our own data presented, we suggest a more cautious interpretation and generalization of the findings by Coras et al. (2014). Nonetheless, it is important to highlight that the clinical and neuropsychological characterization of neuropathological subtypes is an important and necessary approach in establishing the validity and relevance of newly proposed classification systems. In the case of hippocampal sclerosis, the low number of ‘atypical’ subtypes (such as hippocampal sclerosis ILAE Types 2 or 3) calls for multicentric studies supervised by investigators with excellent neuropathological expertise, such as Roland Coras and Ingmar Blu¨mcke from the University Hospital of Erlangen.
Letter to the Editor
Brain 2015: 138; 1–3
| e343
Table 1 Age-corrected presurgical memory performance of patients with hippocampal sclerosis ILAE Type 2 (standard values) Patients with HS ILAE Type 2
Side of surgery
Presurgical verbal memory (VLMT)
Presurgical figural memory (DCS-R)
Learning
Delayed free recall
Loss over time
Recognition
Learning
Recognition
1 2 3 4 5 6
Left Left Left Right Right Right
107 97 81 109 80 95
93 91 66 103 91 99
81 88 77 94 104 97
97 44 79 100 105 104
78 84 84 77 53 68
79 90 84 96 44 61
Impairments (i.e. performance of 41 standard deviation below the mean of the normative sample) are highlighted in bold. HS = hippocampal sclerosis; VLMT = Verbaler Lern- und Merkfa¨higkeitstest; DCS-R = Diagnosticum fu¨r Cerebralscha¨digung – revised.
References Bartsch T, Dohring J, Rohr A, Jansen O, Deuschl G. CA1 neurons in the human hippocampus are critical for autobiographical memory, mental time travel, and autonoetic consciousness. Proc Natl Acad Sci USA 2011; 108: 17562–7. Baxendale SA, Van Paesschen W, Thompson PJ, Duncan JS, Harkness WF, Shorvon SD. Hippocampal cell loss and gliosis: relationship to preoperative and postoperative memory function. Neuropsychiatry Neuropsychol Behav Neurol 1998; 11: 12–21. Blu¨mcke I, Thom M, Aronica E, Armstrong DD, Bartolomei F, Bernasconi A, et al. International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: a task force report from the ILAE commission on diagnostic methods. Epilepsia 2013; 54: 1315–29. Coras R, Pauli E, Li J, Schwarz M, Ro¨ssler K, Buchfelder M, et al. Differential influence of hippocampal subfields to memory formation: insights from TLE patients. Brain 2014; 137: 1945–57. Gleissner U, Helmstaedter C, Elger CE. Right hippocampal contribution to visual memory: a presurgical and postsurgical study in patients with temporal lobe epilepsy. J Neurol Neurosurg Psychiatry 1998; 65: 665–9. Helmstaedter C, Grunwald T, Lehnertz K, Gleissner U, Elger CE. Differential involvement of left temporolateral and temporomesial structures in verbal declarative learning and memory: evidence from temporal lobe epilepsy. Brain Cogn 1997; 35: 110–31. O’Rourke DM, Saykin AJ, Gilhool JJ, Harley R, O’Connor MJ, Sperling MR. Unilateral hemispheric memory and hippocampal neuronal density in temporal lobe epilepsy. Neurosurgery 1993; 32: 574–81. Pauli E, Hildebrandt M, Romstock J, Stefan H, Blu¨mcke I. Deficient memory acquisition in temporal lobe epilepsy is predicted by hippocampal granule cell loss. Neurology 2006; 67: 1383–9. Rausch R, Babb TL. Hippocampal neuron loss and memory scores before and after temporal lobe surgery for epilepsy. Arch Neurol 1993; 50: 812–7.
Remondes M, Schuman EM. Role for a cortical input to hippocampal area CA1 in the consolidation of a long-term memory. Nature 2004; 431: 699–703. Rempel-Clower NL, Zola SM, Squire LR, Amaral DG. Three cases of enduring memory impairment after bilateral damage limited to the hippocampal formation. J Neurosci 1996; 16: 5233–55. Saling MM. Verbal memory in mesial temporal lobe epilepsy: beyond material specificity. Brain 2009; 132: 570–82. Sass KJ, Buchanan CP, Kraemer S, Westerveld M, Kim JH, Spencer DD. Verbal memory impairment resulting from hippocampal neuron loss among epileptic patients with structural lesions. Neurology 1995; 45: 2154–8. Sass KJ, Lencz T, Westerveld M, Novelly RA, Spencer DD, Kim JH. The neural substrate of memory impairment demonstrated by the intracarotid amobarbital procedure. Arch Neurol 1991; 48: 48–52. Sass KJ, Sass A, Westerveld M, Lencz T, Novelly RA, Kim JH, et al. Specificity in the correlation of verbal memory and hippocampal neuron loss: dissociation of memory, language, and verbal intellectual ability. J Clin Exp Neuropsychol 1992; 14: 662–72. Sass KJ, Spencer DD, Kim JH, Westerveld M, Novelly RA, Lencz T. Verbal memory impairment correlates with hippocampal pyramidal cell density. Neurology 1990; 40: 1694–7. Witt JA, Coras R, Schramm J, Becker AJ, Elger CE, Blu¨mcke I, et al. The overall pathological status of the left hippocampus determines preoperative verbal memory performance in left mesial temporal lobe epilepsy. Hippocampus 2014; 24: 446–54. Zaidel DW, Esiri MM, Beardsworth ED. Observations on the relationship between verbal explicit and implicit memory and density of neurons in the hippocampus. Neuropsychologia 1998; 36: 1049–62. Zentner J, Wolf HK, Helmstaedter C, Grunwald T, Aliashkevich AF, Wiestler OD, et al. Clinical relevance of amygdala sclerosis in temporal lobe epilepsy. J Neurosurg 1999; 91: 59–67. Zola-Morgan S, Squire LR, Amaral DG. Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus. J Neurosci 1986; 6: 2950–67.
Copyright of Brain: A Journal of Neurology is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
