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Olfactory discrimination in alcoholic korsakoff patients
Neuropsychologia, 1975, Vol. 13,pp. 173to 179.Pergamon Press.Printedin England.
OLFACTORY DISCRIMINATION IN ALCOHOLIC KORSAKOFF PATIENTS* BARBARA P. JONES,~ HOWARD
R. MOSKOWITZ~
and
NELSON BUTTERS~
‘Psychology Service, Boston V.A. Hospital, Boston, Massachusetts 02130 and Psychology Department, Boston University, Boston, Massachusetts 02215, U.S.A. 2Pioneering Research Laboratory, U.S. Army Natick Laboratories, Massachusetts 01760, U.S.A.
Natick,
sPsychology Service, Boston V.A. Hospital, Boston, Massachusetts 02130 and Aphasia Research Unit, Neurology Department, Boston University School of Medicine, Boston, Massachusetts 02118, U.S.A. (Received 4 July 1974) Abstract-Simple discrimination of various odorants and short-term memory for odors were assessed in alcoholic Korsakoff patients and alcoholic and non-alcoholic controls by means of a sniff-bottle technique. Korsakoff patients demonstrated a striking impairment of olfactory discrimination, scoring at a level no greater than chance on both delay and non-delay conditions. Neither control group showed a significant decay in olfactory STM over a 30-set delay interval. The possibility that the Korsakoffs’ olfactory impairment is related to thalamic and/or hypothalamic damage in this disease is discussed.
INTRODUCTION NEIJROPATHOLOGICAL studies have shown two brain sites to be most consistently damaged in the Wernicke-Korsakoff syndrome: the dorsal medial nucleus of the thalamus (DMN, magnocellular division) and the mammillary bodies (MB, medial portion) [l, 21. VICTOR, ADAMS and COLLINS [2] examined at post-mortem the brains of 43 alcoholic WernickeKorsakoff patients for DMN pathology and found lesions in 88.4 per cent; of 47 cases in the same series examined for MB pathology, 100 per cent were affected. While neuropsychological interest in these patients has focused primarily on their memory deficit, there are anatomical grounds for a consideration of olfactory function in this syndrome. Neuroanatomical studies of primates and rats show how olfactory inputs may reach the DMN and MB [3-71. The olfactory bulb projects to the pyriform cortex via the lateral olfactory tract [3], and the magnocellular division of the DMN in turn receives projections from the pyriform cortex [4]. The pathway to the MB involves efferents from the pyriform cortex to the lateral entorhinal area [4, 51, from the lateral entorhinal area to the hippocampus [6], and from the hippocampus to the MB [7]. In addition the ventral medial nucleus of the thalamus (VMN), damaged in around 60 per cent of WernickeKorsakoff patients [2], receives direct projections from the pyriform cortex, and both DMN
* This study was supported in part by N.I.H. Grant AA00187 to the Boston University School of Medicine. Reprint requests should be addressed to Barbara P. Jones, Psychology Research, Boston V.A. Hospital, 150 So. Huntington Ave., Boston, Mass. 02130. The authors wish to thank Dr. Newell Squires of the Brockton V.A. Hospital for help in locating Korsakoff patients, Guila Glosser for assistance in the final stages of the experiments, and Deborah Glavin for the production of Figure 1. 173
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and VMN send efferent fibers to neocortex, the DMN to orbitofrontal cortex, and the VMN to frontolateral cortex [4]. The present work investigated olfaction in Korsakoff patients for two purposes. One was to ascertain whether olfactory discrimination might be impaired in this syndrome. TALLAND [8] had noted that nine of his Korsakoff patients “seemed to have no capacity for olfactory discrimination”. The second purpose was to investigate short-term memory @TM) in this modality. A recent study by BUTTERS, LEWIS, CERMAK and GOODGLASS [9] has indicated that the Korsakoff patients’ short-term memory (STM) deficit may be material-specific. Whereas Korsakoff patients showed a severe STM deficit for verbal material in the visual, auditory, and haptic modalities, their ability to retain non-verbal material in the same three modalities appeared normal. In the light of this result it seemed pertinent to determine whether alcoholic Korsakoff patients have normal retentive capacities for olfactory information. Since olfactory stimuli appear intuitively to be more isolated from verbal mediation and labels than do stimuli in other modalities, Korsakoff patients might be expected to retain olfactory information more efficiently. Furthermore, in a recent investigation ENGEN, KUISMA and EIMAS [IO] found no decay in STM for odors in normal subjects over a 30-set delay, a result which suggests that STM in this modality is unusually stable.
METHOD Subjects
Three groups of male subjects were assessed: 14 alcoholic Korsakoff patients, 14 alcoholic controls, and 14 non-alcoholic controls. The alcoholic Korsakoff patients had been diagnosed at either the Boston or the Brockton V.A. Hospital and were either in the hospital for treatment or in foster homes. All Korsakoff patients showed severe anterograde and retrograde memory defects and had I.Q.‘s falling within the normal range (mean Full Scale I.Q. on the Wechsler Adult Intelligence Scale = 99.1). The alcoholic controls were patients hospitalized either for the medical complications of alcoholism, usually liver disease, or, in three cases, for psychiatric treatment of their condition. The non-alcoholic subjects were hospitalized patients with no history or symptoms of alcoholism. The groups were matched for average age: Korsakoff patients, 56.8 (range 44-72); alcoholic controls, 54.6 (range 43-65); non-alcoholic controls, 56.5 (range 45-75). This matching was important since the correlation between age and performance on the non-delay section of the olfactory test was significant (r = + 0.31.0.01 < P < 0.05); i.e. younger patients tended to perform better than older patients. Procedure The principal olfactory test utilized 10 odorants in a sniff-bottle technique. The 10 odorants included synthetic and non-synthetic food and spice essences (allspice, black walnut, rosemary, and sage) and chemical compounds (benzaldehyde; l-butanol; butyl acetate; I-decanol; d-p mentha-1,8 diene; and terpinyl acetate). These odorants were chosen to be relatively unfamiliar to the subjects. Initially each odorant was prepared in a solution of 2 ml odorant to 10 ml diethyl phthalate (an odorless diluent). The experimenters then made minor adjustments in concentration so that the subjective intensities of different odorants were approximately the same. A strand of rolled cotton was placed in each odorant solution to facilitate evaporation to an equilibrium level. There were two bottles (12 ml each) of each odorant solution, and all bottles were covered with tape to obscure the contents from the subject. Before the test, tops fitted with Pyrex tubes were screwed on to the bottles, and when the contents of a particular bottle were to be sampled, a handblown Pyrex “sniffer” was fitted over the Pyrex tube [ll]. Two small holes punched into the plastic on either side of the Pyrex tube provided some regulation of the amount of air inhaled in a single sniff. Figure I shows the sniff-bottle apparatus. The test employed the same 20 pairs of stimuli at two delay intervals (0 and 30 set). Zero-delay pairs were given in one block and 30-set delay pairs in another block; for both 0- and 30-see delay tasks there was a 30-set interpair interval. For each pair of stimuli the subject had to decide whether the second stimulus was the same as or different from the first. For 10 of the 20 pairs the two stimuli were the same, and for 10 the two stimuli were different. Table 1 lists the contents of the 20 bottles and gives the 20 test pairings. Before the test each subject* was asked to sniff five common kitchen odorants (cloves; ground coffee * One subject in each group was unable to be given the preliminary test.
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FIG. 1. Sniff-bottle components. The 20 ml bottle is surmounted by a plastic cap which contains a Pyrex tube (note small air holes on either side of tube). Handblown Pyrex “sniffer” is fitted over Pyrex tube. When bottle is not being used, an ordinary cap replaces the tube-cap.
Table 1. Odorant bottles 1. Butyl acetate 2. Rosemary 3. Allspice 4. Sage I-Decanol Z: Rosemary 7. Benzaldehyde 8. Terpinyl acetate Allspice 1:: Butanol 11. Black walnut 12. d-p Mentha-1, 8 diene 13. Butanol 14. Sage 15. Terpinyl acetate 16. Benzaldehyde 17. Black walnut 18. Butyl acetate 19. 1-Decanol 20. d-p Mentha-1, 8 diene
Approximation of odor nail-polish remover rosemary allspice sage fatty, oily rosemary almonds, cherries pungent allspice denatured alcohol black walnut fruity denatured alcohol sage pungent almonds, cherries black walnut nail-polish remover fatty, oily fruity
Test pairs 6-16 8-15 l&2 4-l 3-9 18-17 7-9 4-14 5-19 20-15 11-17 1-18 8-13 12-20 2-6 7-16 3-19 lo-13 11-12 5-14
beans; and orange, peppermint, and vanilla extracts), to state whether or not he could smell each, and finally to identify each odorant. This procedure was intended to provide an independent assessment of the subject’s olfactory function. Each subject then sampled all 10 principal test odorants in order to practice using the bottles and Pyrex attachments with even, reproducible sniffs. For the O-delay section the subject was instructed to sniff the first stimulus of each pair, exhale, and then immediately sniff the second (two Pyrex “sniffers” were used). For the 30-set delay task the Peterson and Peterson distractor technique [12] was employed in order to prevent rehearsal of verbal labels. This technique consisted of having the subject count backwards by three’s from a three-digit number given to him by the experimenter immediately after the first stimulus of a pair. The order of presentation of the two delay tasks was counterbalanced for all groups (0-see delay task first for half the subjects, 30-set delay task first for the other half).
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RESULTS Preliminary test Each subject received two scores on the preliminary, kitchen-odorant test. The first score represented the number of odorants the subject reported he was able to smell (maximum = 5), and the second score tallied his ability to identify the odorants (2 points for each correct identification and 1 point for each near identification, e.g. lemon for orange). Korsakoff patients reported being able to smell a mean of 3.2 odorants as compared to 4.5 for alcoholic controls and 4.6 for non-alcoholic controls. An analysis of variance showed the differences in these means to be significant at the 0.01 level (F = 6.56, df2, 36). The mean identification scores were 1.9 for Korsakoffs, 4.8 for alcoholics, and 5.0 for nonalcoholics (f: = 4.01; df = 2, 36; 0.01 < P < 0.05). Principal test Two analyses were performed on the results of the principal olfactory test. The first analysis of variance considered simple error scores. Figure 2 shows the mean number of o-see oelay
30-set
delay
-
-
IL -
K
FIG.
RC
NBC
K
AC
NAC
2. Mean total errors on the principal olfactory test at both 0- and 30-set delays by Korsakoff
patients, alcoholic controls, and non-alcoholic
controls.
errors for all three groups on both delay tasks. The analysis of variance showed a highly significant group main effect (F = 16.88; df = 2, 39; P < 0.01). Subsequent modified Scheffe t-tests [13] showed that the Korsakoff patients performed significantly worse than both the alcoholic and non-alcoholic subjects (P < 0.001 for both comparisons), but that the alcoholic and non-alcoholic subjects did not differ significantly from each other. Neither the delay effect nor the group x delay interaction was significant. Of particular interest is the lack of a significant delay effect; that is, there was no significant decrement in performance when the delay interval increased from 0 to 30 sec. The second analysis of error scores took into account two types of errors. A false positive error was falsely declaring two different odorants to be the same, while a false negative error was falsely declaring two identical odorants to be different. Thus each subject had four error scores, the number of false positive and false negative errors for each of the two delay tasks. Table 2 shows the distribution of errors in this matrix. A square root transformation was performed on these error scores, and the transformed error scores were then
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PATIENTS
Table 2. Mean error scores 0-set delay False positive Groups Korsakoff patients Alcoholic controls Non-alcoholic controls All
6.3 4.0 1.9 4.1
30-see delay
False negative 2.6 I.6 2.3 2.1
All
8.9 56 4.2 6.2
False positive 4.8 3.6 2.4 3.6
False negative 3.8 2.6 3.1 3.2
All
8.6 6.2 5.6 6.8
analyzed by means of a mixed design analysis of variance [14]. The analysis showed a highly significant group main effect (F = 7.63; df = 2, 39; P = 0.002) and a significant delay x error type interaction (F = 6.39; df = 1, 39; P = O-016). The group x error type interaction approached significance (I; = 2.39; df2,39;P = O-105), but no other main effects or interactions were significant. Modified Scheffe t-tests showed again that in overall performance the Korsakoffs were significantly worse than both alcoholics (P < 0.02) and non-alcoholics (P < O*OOl),whereas the latter two did not differ significantly. The significance of the delay x error type interaction was related to the commission of more false negatives on the 30-set delay task than on the 0-set delay task (P < O-05), while the number of false positive errors was about the same for both delay tasks. On the O-delay task there were significantly more false positive than false negative errors (P < O.OOl),but the number of false positive and negative errors did not differ on the 30-set delay task. Upon examination of the group x error type interaction, it was found that Korsakoff patients committed more false positive errors than false negative erros (P < 0.05) and that the alcoholics also tended toward this pattern, although non-significantly (P < O-20). The non-alcoholics seemed to commit both types of errors with equal frequency. While there were no significant differences among the groups on the number of false negative errors, both the Korsakoff patients and the alcoholic controls made more false positives than did the non-alcoholic controls (P < 0.01, P -c0.05, respectively). DISCUSSION The most striking result of the present study is the Korsakoff patients’ severe impairment in olfactory discrimination. At both delay intervals their performance on the principal olfactory test was at a level no greater than chance (binomial test, P = O-748). This result is supported by the Korsakoff patients’ performance on the preliminary olfactory test, in which they found common kitchen substances difficult to smell and even more difficult to identify. While these findings seem to indicate raised thresholds for olfactory perception in these patients, psychophysical studies are needed to justify this conclusion and are presently being undertaken. A second noteworthy point is the Korsakoff patients’ tendency to commit more false positive than false negative errors. If these patients are, as appears, very impaired in olfactory discrimination, it is reasonable to suppose that different odors tend to smell the same to them. The fact that the alcoholic controls also tended toward this error pattern may suggest that alcohol abuse itself can alter olfactory discrimination to some extent. Whatever the nature of the Korsakoff patients’ olfactory impairment, the implication is that it may be attributable to thalamic, and/or hypothalamic damage characteristic of this
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disease. Animal studies show that from the pyriform cortex, which receives projections from the olfactory bulb via the lateral olfactory tract, there are several pathways for olfactory information. The DMN and VMN pathways seem to be major ones, and both terminate in neocortex. The MB may also receive olfactory inputs via the lateral entorhinal cortex [4, 51 and the hippocampus [6, 71. When damage occurs to the DMN, MB, and possibly VMN, as in the case of the Wernicke-Korsakoff syndrome [2], pathways which are crucial for the processing of olfactory information may be compromised, and the result may be impaired olfactory discrimination. An alternative explanation for these findings must be considered. It is possible that dysosmia in Korsakoff patients may be due to direct damage to the olfactory nerves, bulbs, or tracts. Severe blows to the head, which are common in alcoholics in general, can cause permanent anosmia by shearing of the olfactory nerves as they pass through the cribriform plate, or by disruption of the olfactory bulbs or tracts [15]. The present findings do not, however, support this explanation. The alcoholic controls and the Korsakoff patients were equally likely to have suffered head trauma, yet the alcoholic controls performed significantly better than did the Korsakoff patients on the olfactory tasks. If cranial nerve damage due to trauma were the critical factor in the Korsakoff patients’ olfactory deficit, then alcoholic controls should also have shown a severe olfactory impairment. The recent examination of a traumatic amnesic patient also fails to support the head trauma explanation. This patient has had a dense and permanent anterograde amnesia since suffering head trauma in an automobile accident two years ago. Although the patient has severe visual and auditory STM deficits, his performance on our olfactory task was well within the normal range (error scores of 5 and 6 on the 0- and 30-set delay tasks respectively). It appears then that head trauma sufficient to produce a severe amnesic syndrome is not necessarily sufficient for the impairment of olfactory discrimination. Finally, the present findings point to some important characteristics of normal olfactory memory and discrimination. Unlike visual, auditory, and tactile information which decay rapidly over a 30-set delay interval [9], olfactory stimuli were recognized equally well after 0- and 30-set delays. This result confirms Engen et aI:7 report [IO] of the resistance of olfactory stimuli to STM decay. The present results also indicate that even with 0-see delay, non-alcoholic controls attain a maximum performance of only 80 per cent correct on the olfactory task. This performance level is below that for the same type of task with non-verbal material in the visual, auditory, and haptic modalities [9] and may reflect the fact that man’s capacity to judge stimulus quality is rather poor in the olfactory modality as compared to other modalities [IO]. REFERENCES 1. ADAMS, R. D., COLLINS, G. H. and VICTOR, M. Troubles de la memoire et de l’apprentissage chez I’homme; leurs relations avec des lesions des lobes temporaux et du diencephale. Colloques Internaiionaux du Cerztre National de la Recherche Scientifquc, pp. 273-296. Centre National de la Recherche Scientifique, Paris, 1962. 2. VICTOR, M., ADAMS, R. D. and COLLINS, G. H. The Wetxicke-Korsakoff Syndrome. F. A. Davis, Philadelphia, 1971. 3. MEYER, M. and ALLISON, A. C. Experimental investigation of the connexions of the olfactory tract in the monkey. J. Neural. Neurosurg. Psychiat. 12, 274286, 1949. 4. POWELL, T. P. S., COWAN, W. M. and RAISMAN, G. The central olfactory connexions. J. Anat. 99, 791-813, 196.5. 5. VAN HOESEN, G. W., PANDYA, D. N. and BUTTERS,N. Cortical afferents to the entorhinal cortex of the Rhesus monkey. Science, N.Y. 175, 1471-1473, 1972.
OLFACTORY DTSCRIMINATION IN ALCOHOLIC KORSAKOFF PATIENTS 6. CAJAL,S.R. Studies
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on the Cerebral Cortex. Lloyd-Luke, London, 1955. 7. NAUTA, W. J. H. An experimental study of the fornix system in the rat. J. camp. h’eurol. 104,247-270, 1956. 8. TALLAND,G. A. Deranged Memory. Academic Press, New York, 1965. 9. BUTTERS,N., LEWIS,R., CERMAK,L. S. and GOODGLASS, H. Material-specific memory dsficits in alcoholic Korsakoff patients. Neuropsychologia 11, 291-300, 1973. 10. ENGEN, T., KUISMA,J. E. and EIMAS,P. D. Short term memory of odors. J. exp. Psychol. 99, 222-225, 1973. 11. MOSKOWITZ,H. R. and GERBERS,C. Dimensional salience of odors. Anrr. N.Y. Acad. Sci. 237, 1-16, 1974. 12. PETERSON,L. R. and PETERSON,M. J. Short-term retention of individual verbal items. J. exp. Psycho/. 58, 193-198, 1959. 13. EDWARDS,A. L. Experimental Design in Psychological Research. Holt, Rinehart & Winston, New York, 1964. 14. WINER, B. J. Statistical Principles in Experimental Design. McGraw-Hill, New York, 1971. 15. SCHNEIDER,R. A. Anosmia: verification and etiologies. Ann. Otol. Rhino/. Laryngol. 81,272-277, 1972.
R&m&-On a examink la discrimination simple d’odeurs diverses et la m&moire g court terme pour Ies odeurs chez Ies sujets atteints de syndrome de Korsakoff d’origine alcoolique, chez les alcooliques et chez les contrBles non-alcooliques aux moyens d’une technique utilisant nn flacon permettant de sentir les odeurs. Chez les Korsakoffs, il existait un deficit marqut de la discrimination olfactive, leurs scores n’atteignant pas un niveau plus eleve que celui de la chance aussi bien dans la condition de delai que dans la condition de non delai. Aucun groupe de contrBles ne montrait de diminution significative dans la memoire g court terme olfactive avec un intervalle de 30 sec. On discute la possibilitC que le dtficit olfactif des Korsakoffs dkpende d’une atteinte thalamique et/au hypothalamique. Zusammenfassung-Bei alkoholischen Korsakow-Patienten, Alkoholikern und nichtalkoholischen Kontrollpersonen wurde mit Hilfe einer Riechflaschentechnik das einfache UnterscheidungsvermGgen von verschiedenen Duftstoffen und das Kurzzeitgedlchtnis fiir Duftwahrnehmungen geprfift. Korsakowkranke zeigten ein auffilliges UnvermGgen Duftstoffe zu unterscheiden. Ihre Leistung war weder bei direkter Wahmehmung noch nach VerzGgerung besser. Die Kontrollgruppen IieRen keinen signifikanten AbfaIl des olfaktorischen Duftged&chtnisses fiber 30 Sekunden hinaus erkennen. Es wurde die Mijglichkeit diskutiert, da13 die Korsakowpatienten aufgrund thalamischer oder hypothalamischer SchLden bzw. Schlden in beiden Regionen in ihrem Riechvermijgen beeintrlchtigt sind.
OLFACTORY DISCRIMINATION IN ALCOHOLIC KORSAKOFF PATIENTS* BARBARA P. JONES,~ HOWARD
R. MOSKOWITZ~
and
NELSON BUTTERS~
‘Psychology Service, Boston V.A. Hospital, Boston, Massachusetts 02130 and Psychology Department, Boston University, Boston, Massachusetts 02215, U.S.A. 2Pioneering Research Laboratory, U.S. Army Natick Laboratories, Massachusetts 01760, U.S.A.
Natick,
sPsychology Service, Boston V.A. Hospital, Boston, Massachusetts 02130 and Aphasia Research Unit, Neurology Department, Boston University School of Medicine, Boston, Massachusetts 02118, U.S.A. (Received 4 July 1974) Abstract-Simple discrimination of various odorants and short-term memory for odors were assessed in alcoholic Korsakoff patients and alcoholic and non-alcoholic controls by means of a sniff-bottle technique. Korsakoff patients demonstrated a striking impairment of olfactory discrimination, scoring at a level no greater than chance on both delay and non-delay conditions. Neither control group showed a significant decay in olfactory STM over a 30-set delay interval. The possibility that the Korsakoffs’ olfactory impairment is related to thalamic and/or hypothalamic damage in this disease is discussed.
INTRODUCTION NEIJROPATHOLOGICAL studies have shown two brain sites to be most consistently damaged in the Wernicke-Korsakoff syndrome: the dorsal medial nucleus of the thalamus (DMN, magnocellular division) and the mammillary bodies (MB, medial portion) [l, 21. VICTOR, ADAMS and COLLINS [2] examined at post-mortem the brains of 43 alcoholic WernickeKorsakoff patients for DMN pathology and found lesions in 88.4 per cent; of 47 cases in the same series examined for MB pathology, 100 per cent were affected. While neuropsychological interest in these patients has focused primarily on their memory deficit, there are anatomical grounds for a consideration of olfactory function in this syndrome. Neuroanatomical studies of primates and rats show how olfactory inputs may reach the DMN and MB [3-71. The olfactory bulb projects to the pyriform cortex via the lateral olfactory tract [3], and the magnocellular division of the DMN in turn receives projections from the pyriform cortex [4]. The pathway to the MB involves efferents from the pyriform cortex to the lateral entorhinal area [4, 51, from the lateral entorhinal area to the hippocampus [6], and from the hippocampus to the MB [7]. In addition the ventral medial nucleus of the thalamus (VMN), damaged in around 60 per cent of WernickeKorsakoff patients [2], receives direct projections from the pyriform cortex, and both DMN
* This study was supported in part by N.I.H. Grant AA00187 to the Boston University School of Medicine. Reprint requests should be addressed to Barbara P. Jones, Psychology Research, Boston V.A. Hospital, 150 So. Huntington Ave., Boston, Mass. 02130. The authors wish to thank Dr. Newell Squires of the Brockton V.A. Hospital for help in locating Korsakoff patients, Guila Glosser for assistance in the final stages of the experiments, and Deborah Glavin for the production of Figure 1. 173
BARBARAP. JONES,HOWARDR. MOSKOW~~~ and NELSON BUTTERS
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and VMN send efferent fibers to neocortex, the DMN to orbitofrontal cortex, and the VMN to frontolateral cortex [4]. The present work investigated olfaction in Korsakoff patients for two purposes. One was to ascertain whether olfactory discrimination might be impaired in this syndrome. TALLAND [8] had noted that nine of his Korsakoff patients “seemed to have no capacity for olfactory discrimination”. The second purpose was to investigate short-term memory @TM) in this modality. A recent study by BUTTERS, LEWIS, CERMAK and GOODGLASS [9] has indicated that the Korsakoff patients’ short-term memory (STM) deficit may be material-specific. Whereas Korsakoff patients showed a severe STM deficit for verbal material in the visual, auditory, and haptic modalities, their ability to retain non-verbal material in the same three modalities appeared normal. In the light of this result it seemed pertinent to determine whether alcoholic Korsakoff patients have normal retentive capacities for olfactory information. Since olfactory stimuli appear intuitively to be more isolated from verbal mediation and labels than do stimuli in other modalities, Korsakoff patients might be expected to retain olfactory information more efficiently. Furthermore, in a recent investigation ENGEN, KUISMA and EIMAS [IO] found no decay in STM for odors in normal subjects over a 30-set delay, a result which suggests that STM in this modality is unusually stable.
METHOD Subjects
Three groups of male subjects were assessed: 14 alcoholic Korsakoff patients, 14 alcoholic controls, and 14 non-alcoholic controls. The alcoholic Korsakoff patients had been diagnosed at either the Boston or the Brockton V.A. Hospital and were either in the hospital for treatment or in foster homes. All Korsakoff patients showed severe anterograde and retrograde memory defects and had I.Q.‘s falling within the normal range (mean Full Scale I.Q. on the Wechsler Adult Intelligence Scale = 99.1). The alcoholic controls were patients hospitalized either for the medical complications of alcoholism, usually liver disease, or, in three cases, for psychiatric treatment of their condition. The non-alcoholic subjects were hospitalized patients with no history or symptoms of alcoholism. The groups were matched for average age: Korsakoff patients, 56.8 (range 44-72); alcoholic controls, 54.6 (range 43-65); non-alcoholic controls, 56.5 (range 45-75). This matching was important since the correlation between age and performance on the non-delay section of the olfactory test was significant (r = + 0.31.0.01 < P < 0.05); i.e. younger patients tended to perform better than older patients. Procedure The principal olfactory test utilized 10 odorants in a sniff-bottle technique. The 10 odorants included synthetic and non-synthetic food and spice essences (allspice, black walnut, rosemary, and sage) and chemical compounds (benzaldehyde; l-butanol; butyl acetate; I-decanol; d-p mentha-1,8 diene; and terpinyl acetate). These odorants were chosen to be relatively unfamiliar to the subjects. Initially each odorant was prepared in a solution of 2 ml odorant to 10 ml diethyl phthalate (an odorless diluent). The experimenters then made minor adjustments in concentration so that the subjective intensities of different odorants were approximately the same. A strand of rolled cotton was placed in each odorant solution to facilitate evaporation to an equilibrium level. There were two bottles (12 ml each) of each odorant solution, and all bottles were covered with tape to obscure the contents from the subject. Before the test, tops fitted with Pyrex tubes were screwed on to the bottles, and when the contents of a particular bottle were to be sampled, a handblown Pyrex “sniffer” was fitted over the Pyrex tube [ll]. Two small holes punched into the plastic on either side of the Pyrex tube provided some regulation of the amount of air inhaled in a single sniff. Figure I shows the sniff-bottle apparatus. The test employed the same 20 pairs of stimuli at two delay intervals (0 and 30 set). Zero-delay pairs were given in one block and 30-set delay pairs in another block; for both 0- and 30-see delay tasks there was a 30-set interpair interval. For each pair of stimuli the subject had to decide whether the second stimulus was the same as or different from the first. For 10 of the 20 pairs the two stimuli were the same, and for 10 the two stimuli were different. Table 1 lists the contents of the 20 bottles and gives the 20 test pairings. Before the test each subject* was asked to sniff five common kitchen odorants (cloves; ground coffee * One subject in each group was unable to be given the preliminary test.
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FIG. 1. Sniff-bottle components. The 20 ml bottle is surmounted by a plastic cap which contains a Pyrex tube (note small air holes on either side of tube). Handblown Pyrex “sniffer” is fitted over Pyrex tube. When bottle is not being used, an ordinary cap replaces the tube-cap.
Table 1. Odorant bottles 1. Butyl acetate 2. Rosemary 3. Allspice 4. Sage I-Decanol Z: Rosemary 7. Benzaldehyde 8. Terpinyl acetate Allspice 1:: Butanol 11. Black walnut 12. d-p Mentha-1, 8 diene 13. Butanol 14. Sage 15. Terpinyl acetate 16. Benzaldehyde 17. Black walnut 18. Butyl acetate 19. 1-Decanol 20. d-p Mentha-1, 8 diene
Approximation of odor nail-polish remover rosemary allspice sage fatty, oily rosemary almonds, cherries pungent allspice denatured alcohol black walnut fruity denatured alcohol sage pungent almonds, cherries black walnut nail-polish remover fatty, oily fruity
Test pairs 6-16 8-15 l&2 4-l 3-9 18-17 7-9 4-14 5-19 20-15 11-17 1-18 8-13 12-20 2-6 7-16 3-19 lo-13 11-12 5-14
beans; and orange, peppermint, and vanilla extracts), to state whether or not he could smell each, and finally to identify each odorant. This procedure was intended to provide an independent assessment of the subject’s olfactory function. Each subject then sampled all 10 principal test odorants in order to practice using the bottles and Pyrex attachments with even, reproducible sniffs. For the O-delay section the subject was instructed to sniff the first stimulus of each pair, exhale, and then immediately sniff the second (two Pyrex “sniffers” were used). For the 30-set delay task the Peterson and Peterson distractor technique [12] was employed in order to prevent rehearsal of verbal labels. This technique consisted of having the subject count backwards by three’s from a three-digit number given to him by the experimenter immediately after the first stimulus of a pair. The order of presentation of the two delay tasks was counterbalanced for all groups (0-see delay task first for half the subjects, 30-set delay task first for the other half).
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RESULTS Preliminary test Each subject received two scores on the preliminary, kitchen-odorant test. The first score represented the number of odorants the subject reported he was able to smell (maximum = 5), and the second score tallied his ability to identify the odorants (2 points for each correct identification and 1 point for each near identification, e.g. lemon for orange). Korsakoff patients reported being able to smell a mean of 3.2 odorants as compared to 4.5 for alcoholic controls and 4.6 for non-alcoholic controls. An analysis of variance showed the differences in these means to be significant at the 0.01 level (F = 6.56, df2, 36). The mean identification scores were 1.9 for Korsakoffs, 4.8 for alcoholics, and 5.0 for nonalcoholics (f: = 4.01; df = 2, 36; 0.01 < P < 0.05). Principal test Two analyses were performed on the results of the principal olfactory test. The first analysis of variance considered simple error scores. Figure 2 shows the mean number of o-see oelay
30-set
delay
-
-
IL -
K
FIG.
RC
NBC
K
AC
NAC
2. Mean total errors on the principal olfactory test at both 0- and 30-set delays by Korsakoff
patients, alcoholic controls, and non-alcoholic
controls.
errors for all three groups on both delay tasks. The analysis of variance showed a highly significant group main effect (F = 16.88; df = 2, 39; P < 0.01). Subsequent modified Scheffe t-tests [13] showed that the Korsakoff patients performed significantly worse than both the alcoholic and non-alcoholic subjects (P < 0.001 for both comparisons), but that the alcoholic and non-alcoholic subjects did not differ significantly from each other. Neither the delay effect nor the group x delay interaction was significant. Of particular interest is the lack of a significant delay effect; that is, there was no significant decrement in performance when the delay interval increased from 0 to 30 sec. The second analysis of error scores took into account two types of errors. A false positive error was falsely declaring two different odorants to be the same, while a false negative error was falsely declaring two identical odorants to be different. Thus each subject had four error scores, the number of false positive and false negative errors for each of the two delay tasks. Table 2 shows the distribution of errors in this matrix. A square root transformation was performed on these error scores, and the transformed error scores were then
OLFACTORY
DISCRIMINATION
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PATIENTS
Table 2. Mean error scores 0-set delay False positive Groups Korsakoff patients Alcoholic controls Non-alcoholic controls All
6.3 4.0 1.9 4.1
30-see delay
False negative 2.6 I.6 2.3 2.1
All
8.9 56 4.2 6.2
False positive 4.8 3.6 2.4 3.6
False negative 3.8 2.6 3.1 3.2
All
8.6 6.2 5.6 6.8
analyzed by means of a mixed design analysis of variance [14]. The analysis showed a highly significant group main effect (F = 7.63; df = 2, 39; P = 0.002) and a significant delay x error type interaction (F = 6.39; df = 1, 39; P = O-016). The group x error type interaction approached significance (I; = 2.39; df2,39;P = O-105), but no other main effects or interactions were significant. Modified Scheffe t-tests showed again that in overall performance the Korsakoffs were significantly worse than both alcoholics (P < 0.02) and non-alcoholics (P < O*OOl),whereas the latter two did not differ significantly. The significance of the delay x error type interaction was related to the commission of more false negatives on the 30-set delay task than on the 0-set delay task (P < O-05), while the number of false positive errors was about the same for both delay tasks. On the O-delay task there were significantly more false positive than false negative errors (P < O.OOl),but the number of false positive and negative errors did not differ on the 30-set delay task. Upon examination of the group x error type interaction, it was found that Korsakoff patients committed more false positive errors than false negative erros (P < 0.05) and that the alcoholics also tended toward this pattern, although non-significantly (P < O-20). The non-alcoholics seemed to commit both types of errors with equal frequency. While there were no significant differences among the groups on the number of false negative errors, both the Korsakoff patients and the alcoholic controls made more false positives than did the non-alcoholic controls (P < 0.01, P -c0.05, respectively). DISCUSSION The most striking result of the present study is the Korsakoff patients’ severe impairment in olfactory discrimination. At both delay intervals their performance on the principal olfactory test was at a level no greater than chance (binomial test, P = O-748). This result is supported by the Korsakoff patients’ performance on the preliminary olfactory test, in which they found common kitchen substances difficult to smell and even more difficult to identify. While these findings seem to indicate raised thresholds for olfactory perception in these patients, psychophysical studies are needed to justify this conclusion and are presently being undertaken. A second noteworthy point is the Korsakoff patients’ tendency to commit more false positive than false negative errors. If these patients are, as appears, very impaired in olfactory discrimination, it is reasonable to suppose that different odors tend to smell the same to them. The fact that the alcoholic controls also tended toward this error pattern may suggest that alcohol abuse itself can alter olfactory discrimination to some extent. Whatever the nature of the Korsakoff patients’ olfactory impairment, the implication is that it may be attributable to thalamic, and/or hypothalamic damage characteristic of this
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disease. Animal studies show that from the pyriform cortex, which receives projections from the olfactory bulb via the lateral olfactory tract, there are several pathways for olfactory information. The DMN and VMN pathways seem to be major ones, and both terminate in neocortex. The MB may also receive olfactory inputs via the lateral entorhinal cortex [4, 51 and the hippocampus [6, 71. When damage occurs to the DMN, MB, and possibly VMN, as in the case of the Wernicke-Korsakoff syndrome [2], pathways which are crucial for the processing of olfactory information may be compromised, and the result may be impaired olfactory discrimination. An alternative explanation for these findings must be considered. It is possible that dysosmia in Korsakoff patients may be due to direct damage to the olfactory nerves, bulbs, or tracts. Severe blows to the head, which are common in alcoholics in general, can cause permanent anosmia by shearing of the olfactory nerves as they pass through the cribriform plate, or by disruption of the olfactory bulbs or tracts [15]. The present findings do not, however, support this explanation. The alcoholic controls and the Korsakoff patients were equally likely to have suffered head trauma, yet the alcoholic controls performed significantly better than did the Korsakoff patients on the olfactory tasks. If cranial nerve damage due to trauma were the critical factor in the Korsakoff patients’ olfactory deficit, then alcoholic controls should also have shown a severe olfactory impairment. The recent examination of a traumatic amnesic patient also fails to support the head trauma explanation. This patient has had a dense and permanent anterograde amnesia since suffering head trauma in an automobile accident two years ago. Although the patient has severe visual and auditory STM deficits, his performance on our olfactory task was well within the normal range (error scores of 5 and 6 on the 0- and 30-set delay tasks respectively). It appears then that head trauma sufficient to produce a severe amnesic syndrome is not necessarily sufficient for the impairment of olfactory discrimination. Finally, the present findings point to some important characteristics of normal olfactory memory and discrimination. Unlike visual, auditory, and tactile information which decay rapidly over a 30-set delay interval [9], olfactory stimuli were recognized equally well after 0- and 30-set delays. This result confirms Engen et aI:7 report [IO] of the resistance of olfactory stimuli to STM decay. The present results also indicate that even with 0-see delay, non-alcoholic controls attain a maximum performance of only 80 per cent correct on the olfactory task. This performance level is below that for the same type of task with non-verbal material in the visual, auditory, and haptic modalities [9] and may reflect the fact that man’s capacity to judge stimulus quality is rather poor in the olfactory modality as compared to other modalities [IO]. REFERENCES 1. ADAMS, R. D., COLLINS, G. H. and VICTOR, M. Troubles de la memoire et de l’apprentissage chez I’homme; leurs relations avec des lesions des lobes temporaux et du diencephale. Colloques Internaiionaux du Cerztre National de la Recherche Scientifquc, pp. 273-296. Centre National de la Recherche Scientifique, Paris, 1962. 2. VICTOR, M., ADAMS, R. D. and COLLINS, G. H. The Wetxicke-Korsakoff Syndrome. F. A. Davis, Philadelphia, 1971. 3. MEYER, M. and ALLISON, A. C. Experimental investigation of the connexions of the olfactory tract in the monkey. J. Neural. Neurosurg. Psychiat. 12, 274286, 1949. 4. POWELL, T. P. S., COWAN, W. M. and RAISMAN, G. The central olfactory connexions. J. Anat. 99, 791-813, 196.5. 5. VAN HOESEN, G. W., PANDYA, D. N. and BUTTERS,N. Cortical afferents to the entorhinal cortex of the Rhesus monkey. Science, N.Y. 175, 1471-1473, 1972.
OLFACTORY DTSCRIMINATION IN ALCOHOLIC KORSAKOFF PATIENTS 6. CAJAL,S.R. Studies
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on the Cerebral Cortex. Lloyd-Luke, London, 1955. 7. NAUTA, W. J. H. An experimental study of the fornix system in the rat. J. camp. h’eurol. 104,247-270, 1956. 8. TALLAND,G. A. Deranged Memory. Academic Press, New York, 1965. 9. BUTTERS,N., LEWIS,R., CERMAK,L. S. and GOODGLASS, H. Material-specific memory dsficits in alcoholic Korsakoff patients. Neuropsychologia 11, 291-300, 1973. 10. ENGEN, T., KUISMA,J. E. and EIMAS,P. D. Short term memory of odors. J. exp. Psychol. 99, 222-225, 1973. 11. MOSKOWITZ,H. R. and GERBERS,C. Dimensional salience of odors. Anrr. N.Y. Acad. Sci. 237, 1-16, 1974. 12. PETERSON,L. R. and PETERSON,M. J. Short-term retention of individual verbal items. J. exp. Psycho/. 58, 193-198, 1959. 13. EDWARDS,A. L. Experimental Design in Psychological Research. Holt, Rinehart & Winston, New York, 1964. 14. WINER, B. J. Statistical Principles in Experimental Design. McGraw-Hill, New York, 1971. 15. SCHNEIDER,R. A. Anosmia: verification and etiologies. Ann. Otol. Rhino/. Laryngol. 81,272-277, 1972.
R&m&-On a examink la discrimination simple d’odeurs diverses et la m&moire g court terme pour Ies odeurs chez Ies sujets atteints de syndrome de Korsakoff d’origine alcoolique, chez les alcooliques et chez les contrBles non-alcooliques aux moyens d’une technique utilisant nn flacon permettant de sentir les odeurs. Chez les Korsakoffs, il existait un deficit marqut de la discrimination olfactive, leurs scores n’atteignant pas un niveau plus eleve que celui de la chance aussi bien dans la condition de delai que dans la condition de non delai. Aucun groupe de contrBles ne montrait de diminution significative dans la memoire g court terme olfactive avec un intervalle de 30 sec. On discute la possibilitC que le dtficit olfactif des Korsakoffs dkpende d’une atteinte thalamique et/au hypothalamique. Zusammenfassung-Bei alkoholischen Korsakow-Patienten, Alkoholikern und nichtalkoholischen Kontrollpersonen wurde mit Hilfe einer Riechflaschentechnik das einfache UnterscheidungsvermGgen von verschiedenen Duftstoffen und das Kurzzeitgedlchtnis fiir Duftwahrnehmungen geprfift. Korsakowkranke zeigten ein auffilliges UnvermGgen Duftstoffe zu unterscheiden. Ihre Leistung war weder bei direkter Wahmehmung noch nach VerzGgerung besser. Die Kontrollgruppen IieRen keinen signifikanten AbfaIl des olfaktorischen Duftged&chtnisses fiber 30 Sekunden hinaus erkennen. Es wurde die Mijglichkeit diskutiert, da13 die Korsakowpatienten aufgrund thalamischer oder hypothalamischer SchLden bzw. Schlden in beiden Regionen in ihrem Riechvermijgen beeintrlchtigt sind.