Downloaded from learnmem.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press RESEARCH Sensorimotor Skill Learning in Amnesia: Additional Evidence for the Neural Basis of Nondeclarative Memory Daniel Tranel, 1 Antonio R. Damasio, Hanna Damasio, and Joan P. Brandt Department of Neurology Division of Behavioral Neurologyand Cognitive Neur0science University of I0wa College of Medicine I0wa City, I0wa 52242 Abstract Introduction We investigated sensorimotor skill A number of investigations have established learning, a form of nondeclarative (implicit) that the learning of new skills can be preserved in memory, in 28 subjects with declarative patients who are unable to learn new words, faces, (explicit) memory defects caused by either and facts (e.g., Corkin 1965, 1968; MilDer 1972; mesial temporal (n = 15) or basal forebrain Cermak et al. 1973; Cohen and Squire 1980; Mar- (n=13) damage and in 66 normal control tone et al. 1984; Eslinger and Damasio 1986; Ga- subjects. All 28 amnesics had normal brieli et al. 1993; for reviews, see Baddeley 1982; learning of a rotor pursuit task. We also Hintzman 1990; Shimamura 1990; Cohen and studied in detail the sensorimotor skill Eichenbaum 1993). The concepts of "declarative" learning of patient Boswell. As a result of and "nondeclarative" memory have been used to bilateral damage to both mesial and lateral refer to the different types of information and task aspects of the temporal lobes and to the demands that are dissociated in such patients basal forebrain, Boswell has one of the most (Squire 1992). Declarative memory refers to rep- severe impairments ever reported for resentations of facts and events that can only be learning of all types of declarative brought to mind in image form. Nondeclarative knowledge. Compared to matched controls, memory pertains to information that is not ame- Boswell acquired and retained normally the nable to imagetic representation. Sensorimotor skills associated with performing motor skills, which refer to the knowledge of how to tasks. We conducted a long-term (2-year) perform a motor task, require nondeclarative followup study of Boswell's retention of the memory. Only the factual information associated rotor pursuit task, and we found that he with the acquisition of the task requires declara- retained the skill as well as normal controls. tive memory (Cohen and Squire 1980; Squire Our study builds on previous work in 1992). Another way to conceptualize this distinc- the following respects: (1) It provides tion is along a dimension of "explicit" and "im- evidence, for the first time, that skill plicit," where explicit corresponds to declarative learning is normal in basal forebrain and implicit corresponds to nondeclarative (e.g., amnesics; (2) it shows that patient Boswell Schacter 1987). has normal learning and long-term The dissociation between declarative and retention of sensorimotor skills, in spite of nondeclarative memory in brain-damaged patients his extensive damage; and (3) it offers has led to the proposal that the neural systems additional evidence that mesial temporal underlying the two types must be different (Es- lobe damage spares skill learning. These linger and Damasio 1986; Damasio 1989; Damasio findings demonstrate unequivocally that et al. 1989; Squire 1992; Petri and Mishkin 1994). sensorimotor skill learning does not There is evidence that the mesial temporal system, require structures in mesial and lateral which includes the entorhinal and perirhinal cor- temporal regions nor in basal forebrain. tices, hippocampus proper, parahippocampal gy- rus, and amygdala and which is critical for the 1Corresponding author. acquisition of declarative information, is not Dec- LEARNING & MEMORY 1:165-179 © 1994 by Cold Spring Harbor Laboratory Press ISSN1072-0502/94 $5.00 L E A R N I N G & M E M O R Y 165 Downloaded from learnmem.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press Tranel et al. essary for skill learning. Damage to mesial tempo- vision of Behavioral Neurology and Cognitive Neu- ral structures from surgical ablation (e.g., Milner roscience. The criterion for selection was the pres- 1972) or Alzheimer's disease (e.g., Eslinger and ence of damage (unilateral or bilateral) in the Damasio 1986; Gabrieli et al. 1993) does not pre- mesial temporal region (entorhinal/perirhinal cor- clude normal learning of motor skills. There is also tices, hippocampus, parahippocampal gyrus, and evidence that medial diencephalic damage of the amygdala) or basal forebrain, as determined by our type associated with alcoholic Korsakofl~'s syn- standard method of lesion analysis (Damasio and drome, which typically produces a severe amnesia Damasio 1989; Damasio and Frank 1992). In addi- for declarative material, is compatible with normal tion, we conducted detailed studies of patient skill learning (Martone et al. 1984; for review, see Boswell (see below). Butters and Stuss 1989). Moreover, the cerebellum and neostriatum, which are intact in the various patients cited MESIAL TEMPORAL LOBE above, have been implicated as crucial structures underlying acquisition of motor skills (McCormick Fifteen subjects with mesial temporal lobe le- and Thompson 1984; Eslinger and Damasio 1986; sions were studied. The demographic information Thompson 1986; Saint-Cyr et al. 1988; Sanes et al. for this group is provided in the upper part of 1990; Seitz et al. 1990; Schmahmann 1991; Fiez et Table 1. Pertinent data regarding neuropsycholog- al. 1992; Grafman et al. 1992; Saint-Cyr and Taylor ical status are presented in the upper part of Table 1992; Heindel et al. 1993; Pascual-Leone et al. 2. These data were interpreted by one of us (D.T.) 1993), although not all studies have produced who was "blind" to details of the subjects' lesions, consistent findings (Daum et al. 1993). On the using standard normative information that takes other hand, nothing is known about the possible into account age, gender, and estimated premor- contribution to skill learning, of structures such as bid intelligence (Lezak 1983; Spreen and Strauss the basal forebrain or the nonmesial temporal cor- 1991; Tranel 1994). As the data in Table 2 indi- tices, whose damage is known to compromise de- cate, the subjects have significant declarative clarative memory (Damasio et al. 1985a,b, 1989). memory impairments. In general, the memory de- In this paper we report an investigation of sen- fects show the expected pattern of material spec- sorimotor skill learning in 15 subjects with dam- ificity; that is, subjects with left-sided lesions age to the mesial temporal lobe and 13 with dam- tended to have more impairment for verbally age to basal forebrain. We also conducted a de- based material, and subjects with right-sided le- tailed investigation of patient Boswell, whose sions tended to have more impairment for nonver- bilateral lesions to mesial and lateral temporal lobe bal, visuospatial material. as well as basal forebrain structures have produced Details of the neuroanatomical status of these one of the most profound anterograde and retro- subjects are presented in the upper portion of Ta- grade amnesic syndromes ever reported. The nor- ble 3. All subjects have unilateral (six, left; seven, mal skill learning that we found in all subjects right) or bilateral (n - 2) mesial temporal damage, demonstrates unequivocally that sensorimotor affecting all or parts of the entorhinal and perirhi- skill learning does not require structures in mesial nal cortices, hippocampus, parahippocampal gy- and lateral temporal regions nor in basal forebrain. rus, and amygdala. Etiologic information is also The findings also support the notion that the brain provided in Table 3; most of the subjects had honors a fundamental distinction between infor- herpes simplex encephalitis, anoxia/ischemia, or mation that can only be recalled in imagetic form temporal lobectomy. and information that can be recorded as a motor output. BASAL FOREBRAIN Materials and Methods Thirteen subjects with presumed basal fore- brain damage were studied. Demographic informa- tion for this group is provided in the lower portion SUBJECTS of Table 1. Neuropsychological findings are pre- The subjects for this study were selected from sented in the lower part of Table 2. As in the case the Patient Registry of the University of Iowa's Di- of the temporal lobe subjects, the neuropsycho- L E A R N I N G & M E M O R Y 166 Downloaded from learnmem.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press NEURAL BASIS OF NONDECLARATIVE MEMORY Table 1: Demographic information Side of Group lesion a Age/gender Handedness b Education Chronicity c Temporal lobe LR-488 71/F + 90 16 4 years LV-580 31/F + 100 14 4 years JM-858 41/M + 100 16 6 years AN-1033 27/M + 100 8 4 years UB-1251 35/M + 100 12 4 years CS-1404 19/M + 100 13 2 years MM-621 44/M + 100 12 6 years LDV-692 20/F + 100 12 3 years DM-727 37/M + 100 12 3 years RH-747 45/M + 100 14 9 years TJ-1191 65/M + 100 12 4 months MR-1323 71/F + 100 10 2 years FR-1465 61/M + 100 14 11 months FDH-1337 40/M + 100 18 4 years RI-1746 26/M + 100 12 7 months Basal forebrain RF-297 L 38/M + 100 16 7 years RG-1197 R 32/M + 100 16 10 years DM-1209 R 38/F + 60 12 1 year WM-415 B 49/M - 70 11 2 years MR-429 B 55/F + 100 12 6 years VY-500 B 58/F + 100 12 5 years SM-501 B 38/M + 100 12 15 months HS-1065 B 55/F + 100 8 5 years FL-1164 B 75/F + 100 12 5 years BY-1262 B 31/F + 100 14 2 years SB-1281 B 62/F + 20 12 3 years DM-1336 B 82/M + 100 9 12 years RS-1479 B 63/F + 100 8 4 years a(L) Left; (R) right; (B) bilateral.