Brain (1997), 120, 1845–1856
Contribution of medial versus lateral temporal-lobe
structures to human odour identification
M. Jones-Gotman,1 R. J. Zatorre,1 F. Cendes,1 A. Olivier,1 F. Andermann,1 D. McMackin,2 H.
Staunton,2 A. M. Siegel3 and H.-G. Wieser3
1McGill
University and Montreal Neurological Institute,
Montreal, Quebec, Canada, 2Richmond Institute of
Neurology and Neurosurgery, Beaumont Hospital, Dublin,
Ireland and 3University Hospital, Department of Neurology,
Zurich, Switzerland
Correspondence to: M. Jones-Gotman, Montreal
Neurological Institute, 3801 University Street, Montreal,
Quebec, Canada H3A 2B4
Summary
To investigate possible distinct contributions of different
temporal-lobe structures to odour identification, the
University of Pennsylvania Smell Identification Test was
administered monorhinally to seizure-free patients who had
undergone one of three types of temporal-lobe resection
practised in three different institutions for surgical treatment
of epilepsy. The resections were neocorticectomy (Dublin),
selective amygdalohippocampectomy (Zurich), or anterior
temporal-lobe resection with encroachment on amygdala and
hippocampus (Montreal). Resections, analysed from MRI
scans, showed unexpected encroachment on medial structures
in most patients of the neocorticectomy groups, and largest
amygdala and hippocampal resections in the amygdalo-
hippocampectomy groups. Impaired odour identification was
observed in all patient groups, irrespective of surgical
approach, with greatest impairment in the nostril ipsilateral
to the resection. The finding of deficits in all three surgical
groups suggests that damage in the anterior temporal area,
perhaps in piriform cortex, is sufficient to disrupt performance
on this task; it may be that function is disrupted in the
medial temporal-lobe region by disconnection when the
periamygdaloid area is damaged, even when amygdala and
hippocampus are left intact. An alternative explanation for
our results is that damage in any one of these areas disrupts
a complex network involving several distinct temporal-lobe
structures.
Keywords: olfaction; temporal lobes; amygdala; hippocampus; epilepsy
Abbreviation: UPSIT 5 University of Pennsylvania Smell Identification Test
Introduction
The sense of smell, highly developed in many mammals,
takes a back seat to the other senses in primates, and
especially in humans. Nevertheless, recent studies of human
olfaction show that odours play a significant, if often subtle,
role in human behaviour. Mood can be manipulated by
ambient odour (Kirk-Smith and Booth, 1987; Mitchell et al.,
1995; Spangenberg et al., 1996; Baron, 1997); people can
recognize a spouse or members of their family by smell
(Schleidt, 1980; Porter et al., 1986; Schaal and Porter, 1991),
infants can recognize their mothers (Schaal, 1988), and
mothers their infants by smell (Porter et al., 1983; Russell,
et al., 1983), and odours convey information about the
environment, including information important for survival,
such as alerting one to spoiled food, or to fire or pollution.
The ability to identify the source of odours thus remains an
important function for humans.
© Oxford University Press 1997
Brain regions involved in processing olfactory information
in human subjects have been investigated in several studies;
these have shown that the important cortical areas are within
the frontal and temporal lobes. Studies of patients with
surgical lesions in the temporal lobes have provided evidence
of a temporal-lobe role in odour discrimination (Rausch,
et al., 1977; Zatorre and Jones-Gotman, 1991; Martinez et al.,
1993), odour memory (Carroll and Richardson, 1993; JonesGotman and Zatorre, 1993; Martinez et al., 1993), and odour
identification (Eskenazi et al., 1983, 1986; Jones-Gotman
and Zatorre, 1988; Martinez et al., 1993). Furthermore, a
relative predominance of one hemisphere over the other,
most often the right over the left, has been observed in some
olfactory tasks. This has been shown in lesion studies of
patients with temporal-lobe resection, where olfactory deficits
were confined to (Abraham and Mathai, 1983; Carroll and
1846
M. Jones-Gotman et al.
Richardson, 1993; Jones-Gotman and Zatorre, 1993), or
greater in (Rausch et al., 1977) patients with right-sided
excision. It has also been shown in healthy subjects, in whom
an advantage was demonstrated favouring the right nostril in
odour discrimination (Zatorre and Jones-Gotman, 1990).
Also in healthy subjects, cerebral blood flow changes were
demonstrated unilaterally in right orbitofrontal cortex, as well
as bilaterally in piriform cortex, upon birhinal inhalation of
odours in a PET study (Zatorre et al., 1992).
In contradiction to the above findings, there are lesion
studies in which no significant differences were found
between left- and right-sided temporal-lobe resections
(Eskenazi et al., 1983, 1986; Jones-Gotman and Zatorre,
1988), and deficits only after left temporal lobectomy have
also been reported (Henkin et al., 1977). Furthermore, there
are reports of impairments after both left- and right-sided
resections, in which the deficits were confined to the nostril
ipsilateral to surgery (Eskenazi et al., 1986; Zatorre and
Jones-Gotman, 1991; Martinez et al., 1993). Thus, although
the right hemisphere appears to exercise some advantage
over the left in at least some olfactory tasks, this is not true
under all conditions.
Whereas it now seems clear that neural systems within the
temporal lobe play a significant role in human olfaction,
the specific contributions of different structures within the
temporal lobe are still unknown. In the animal literature, the
primary temporal-lobe areas involved in olfaction are the
piriform cortex, the uncus, the amygdala and the entorhinal
area (Eslinger et al., 1982; Price, 1985, 1990; Switzer et al.,
1985), but confirmation that these areas are important in
human olfaction is sparse; one lesion study provided some
indirect evidence suggesting that the right amygdala is
important in human odour memory (Jones-Gotman and
Zatorre, 1993), and one PET study with healthy volunteers
revealed activity in the right hippocampal region during an
odour memory task (Jones-Gotman et al., 1993).
The ability to identify odours should share some of the
cerebral functions active in odour memory, because one must
remember an odour before it is possible to identify its source.
In a previous study we investigated odour identification in
patients with temporal-lobe excisions that included temporal
neocortex and amygdala, and varying extents of encroachment
on the hippocampus (up to ~2.5 cm, according to the surgeon’s
estimate at operation) (Jones-Gotman and Zatorre, 1988). We
explored the effect of hippocampal excision by dividing
patients into two groups depending on the size of hippocampal
resection, and analysing their performance on a standardized
odour identification test. We found deficits in all groups
without respect to extent of hippocampal resection or to side
of resection; the four groups were virtually indistinguishable
from one another. Those results suggested that the temporal
cortex is important for odour identification, and that the
hippocampus does not seem to play a specific or additional
role in this function. However, they provided no information
about amygdala, since it was excised in both the small and
large hippocampal groups. Also, any possible distinctive
contributions of neocortex and of hippocampus were
confounded in the same way.
To examine the notion that some temporal-lobe structures
may contribute significantly to odour identification and others
not, in the present study we analysed the performance of
three populations of patients with different types of surgical
excision from the temporal lobes. One population, located in
Montreal, Canada, consisted again of patients with anterior
temporal-lobe resection including amygdala and some
hippocampus (Olivier, 1988). A second one, in Dublin,
Ireland, was made up of patients who had undergone temporal
neocorticectomy, which is intended to spare both the
amygdala and hippocampus (Hardiman et al., 1988; Keogan
et al., 1992). The third population comprised patients in
Zurich, Switzerland, who had undergone selective resection
from the medial basal temporal region, sparing the temporal
neocortex (Wieser and Yasargil, 1982; Yasargil et al., 1985).
We predicted that the population of patients whose medial
structures were spared would perform normally on the odour
identification test, while both other populations of patients
would show impairments, reasoning that the medial, but not
the lateral, temporal lobe would be important for performing
the task. We also predicted that deficits would be confined
to, or greater in, the nostril ipsilateral to surgical excision,
but based on our previous findings of equal (birhinal)
impairments in left and right temporal-lobe excision groups,
we predicted that the monorhinal test would reveal ipsilateral
deficits in both left- and right-sided resection groups.
Methods
Subjects
Seventy patients participated in the main study. They were
selected on the basis of their surgical outcome with respect
to seizure control; only patients who had been seizure-free
for at least 18 months were included. We also attempted to
ensure that all patients were of normal intelligence, excluding
individuals with a Full-Scale IQ ,80 (Wechsler, 1955, 1981)
when possible. This criterion could not be used in Zurich,
where IQ testing is not usually carried out; however, all of
those patients had completed formal schooling except one,
who had finished 8 years of school. All subjects were
screened for normal odour detection thresholds (comparing
phenylethyl alcohol and water); one subject, from an initial
sample of 71, was excluded owing to anosmia.
To control for possible cultural or linguistic differences
among the three geographical sites that might affect odour
identification, 40 healthy control subjects were also tested,
one group for each patient population. Taking education level
as a rough estimate of intellectual abilities, we attempted
to match each control group to its corresponding patient
population as closely as possible for education and for
age. However, they did differ on the education variable
[F(2,101) 5 9.4], but analysis of covariance on the
performance data, using education as the covariate, showed
Odour identification
that education level did not contribute significantly to our
results (F 5 0.88).
In addition to the subjects in the main study, 36 unoperated
patients with temporal-lobe epilepsy (in Montreal) were
included to explore the effect of an unresected temporal-lobe
seizure focus on olfactory performance. Those patients were
classified as having a left- or a right-sided focus based on
EEG and clinical criteria (e.g. seizure pattern, and
neuroimaging when available).
Informed consent was obtained from all subjects, and the
study received ethical approval from the three participating
centres. Demographic information for all subject groups is
shown in Table 1.
The three different surgical approaches in the treatment of
these patient groups, as habitually described by the respective
institutions, will be reported briefly below, followed by our
evaluation of the extent and location of the resections as
shown on MRI films. The former reflects the expected
resection for each of the three groups, while the latter
describes the actual anatomical findings.
In patients with anterior temporal-lobe resection (the
Montreal group), the aim was to excise the first, second and
third temporal gyri (anteriorly), together with total or partial
resection of amygdala and uncus, and varying encroachment
on hippocampus and parahippocampal gyrus, depending on
the needs of the individual case (Olivier, 1988).
In the temporal neocorticectomy patients (the Dublin
group), the area of resection included the lower half of the
superior temporal gyrus along with the middle and inferior
temporal gyri, sparing the upper half of the superior temporal
gyrus. The aim in this operation is to expose amygdala and
anterior hippocampus, but to leave both unresected (Hardiman
et al., 1988; Keogan et al., 1992).
In the amygdalohippocampectomy patients (the Zurich
group), structures targeted for removal were amygdala,
hippocampus and parahippocampal gyrus (Wieser and
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Yasargil, 1982; Siegel et al., 1990). The target area was
approached via the Sylvian fissure, leaving the lateral
temporal neocortex untouched.
Figures 1–3 show coronal sections, approximately at a
level where both amygdala and hippocampus are visible,
from postoperative MRI scans of two patients from each
centre. Each two patients represent the least and most
extensive resections from that centre, without respect to side
of surgical resection.
As may be appreciated in the figures, the scans from the
Dublin patients (Fig. 1) revealed unexpected encroachment
on medial structures in some cases (Fig. 1, right).
Furthermore, near-sparing of medial structures, including
most of the amygdala, was noted in some Montreal cases
(see example in Fig. 2, left). Thus, a certain degree of overlap
between the surgical excisions of the Dublin and Montreal
cases existed despite the nominally distinct nature of the
surgical procedures.
The method we have used to quantify and characterize the
locus and extent of the surgical resections consists of an
anatomically based grid overlaid on the MRI scans (Lehman
et al., 1992). This is established by a series of lines and
planes using the corpus callosum as a landmark. Based on
the scout image and sagittal views, a horizontal plane is
constructed through the inferior border of the genu and
splenium. Two vertical planes are created, perpendicular to
the horizontal plane; an anterior callosal plane tangential to
the anterior border of the genu, and a posterior callosal plane
tangential to the posterior border of the splenium. Eight
evenly spaced coronal slices were identified between these
two planes, and each one was divided into four sections:
superomesial, superolateral, inferolateral and inferomesial.
The percentage removal of the structures in each section was
calculated and this was used to estimate the amount of
resection.
The basolateral temporal cortex was arbitrarily divided
Table 1 Subjects
Groups
Dublin
Control subjects
Left-sided resection
Right-sided resection
Montreal
Control subjects
Left-sided resection
Right-sided resection
Zurich
Control subjects
Left-sided resection
Right-sided resection
Unoperated patients
Left-sided focus
Right-sided focus
*Non-right
Female :
male (n)
Handedness
(R : Non-R*)
Age (years)
Mean (range)
Education (years)
Mean (range)
Incidence
of tumour
10 : 6
6:6
4:6
16 : 0
11 : 1
10 : 0
24.6 (17–40)
28.8 (17–52)
28.9 (22–34)
14.3 (10–17)
12.4 (10–15)
12.5 (11–16)
NA
0
0
8:5
3:8
10 : 2
11 : 2
10 : 1
10 : 2
31.5 (20–47)
35.4 (25–44)
30.4 (19–42)
14.5 (10–18)
13.9 (6–22)
11.4 (8–16)
NA
1
1
7:4
8:3
8:6
11 : 0
9:2
13 : 1
29.3 (19–49)
30.7 (15–48)
35.3 (17–48)
13.9 (9–19)
12.0 (8–16)
11.1 (8–14)
NA
3
1
9:9
12 : 6
15 : 3
17 : 1
31.3 (14–49)
28.1 (14–48)
12.9 (7–18)
12.1 (7–16)
3
0
handed subjects include those who switched from left to right for writing.
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M. Jones-Gotman et al.
Fig. 1 MRI scan coronal sections, at a level showing the amygdala, from the two patients in the neocorticectomy group (Dublin) having
the least and most extensive resection from medial structures. Left: patient with right neocorticectomy; no removal from amygdala,
hippocampus or parahippocampal gyrus. Right: patient with left neocorticectomy; removal from amygdala, hippocampus and
parahippocampal gyrus were 52.5%, 25% and 97.5%, respectively (all measurements are the mean from two observers, see text).
into (i) anterior, or pole (consisting of all four sections of
slices 1 and 2); (ii) middle (superolateral and inferolateral
sections of slices 3–5); and (iii) posterior (superolateral and
inferolateral sections of slices 6–8). The parahippocampal
gyrus and entorhinal cortex, which were measured together,
were located within the inferomesial section of slices 3–7;
the amygdala was within the superomesial section of slices
3 and 4 and at times also slice 5; the hippocampus was
within the inferomesial section of slices 4–8. The sections
and anatomical divisions used in this method are shown in
Fig. 4.
The measurements were performed independently by two
of us (F.C. and A.M.S.) and submitted to a correlation
analysis to establish inter-observer reliability. The resulting
correlations were high (anterior temporal, r 5 0.83; midbasal,
r 5 85; posterior basal, r 5 0.81; hippocampus, r 5 0.78;
parahippocampal region, r 5 0.79; amygdala, r 5 0.78; P
, 0.05 in all cases). These results assured us that the
measurements were reliable. For subsequent analyses we
averaged the measurements of the two observers, for each
patient in each region of interest. The extent of removal in
each measured region was compared across centres by
ANOVA, which examined the amount of removal as a
function of resection type and side of surgery. These
measurements confirmed considerable overlap among the
three types of surgical approach, in resection from medial
structures. Figures 5–7 show the average measurements (for
each centre), together with all data points, for amygdala,
hippocampus and parahippocampal gyrus. Figures 8–10 show
the same data for the three measured lateral neocortex regions,
for Dublin and Montreal only.
Although an overlap was expected in the Montreal and
Zurich resections, the amount of medial temporal removal in
the Dublin cases was not anticipated. In fact, among the 22
Dublin patients, medial structures were spared in only five
cases (complete sparing was defined as ,15% encroachment
on any of the three measured medial regions). The most
highly significant difference in removal extent was observed
in the amygdala (more complete in Zurich cases than in
Montreal or Dublin [F(2,61) 5 22.45, P , 0.0001], with a
similar pattern in hippocampal removals [F(2,61) 5 23.42,
P , 0.001]. There were no significant differences across the
three excision types in the amount of parahippocampal gyrus
excision. Also, for each measured region, there were no
Odour identification
1849
Fig. 2 MRI scan coronal sections, at a level showing the amygdala, from the two patients in the anterior temporal-lobe resection group
(Montreal) having the least and most extensive resection from medial structures. Left: patient with left anterior temporal-lobe resection;
removal from amygdala, hippocampus and parahippocampal gyrus were 15%, 10% and 15%, respectively. Right: patient with right
anterior temporal-lobe resection; removals were 92.5%, 68.5% and 79%.
differences between left- and right-sided resections in the
amount of tissue excised.
Test material
Odour identification was tested using the University of
Pennsylvania Smell Identification Test (UPSIT) (Doty et al.,
1984). This is a standardized set of 40 common and familiar
odorants, which are embedded in ‘scratch and sniff’ fragrance
labels and assembled in booklets. The odours are released
when the labels are scratched. The test is in a multiple-choice
format, with four written response alternatives for each odour.
The three distracter items for each odorant were highly
distinct from one another and from the target stimulus. We
used an answer sheet that was separate from the fragrancelabel booklets to keep the testing conditions the same for
English- and French- or Swiss-German-speaking subjects,
for whom we had translated the response alternatives.
The UPSIT was administered monorhinally in this
experiment. One nostril was blocked completely with
Microfoam surgical tape (3M) while subjects inhaled with
the free nostril. This was done in blocks of five, so that the
tape (and nostril) was changed after every five odours. In
all, 20 stimuli were presented to the left nostril and 20 to
the right. Subjects sniffed each odour twice: after the first
sniff they reported their affective response to the odour using
rating scales provided for that purpose. Before the second
sniff they were given the answer sheet and were asked to
sniff again before selecting the odour that they had smelled
from among the four alternatives. The affective responses
are part of a separate study and will not be reported here.
Results
Performance of normal control groups
Because this test was designed for a North American
population, an item analysis was performed, separately for
each control group, to determine whether or not any specific
odours might have been unfamiliar to that population. For
the European populations, all items were eliminated on which
the relevant control group performed at chance levels. Five
items were eliminated for Irish subjects: these were
fruitpunch, Cheddar cheese, dill pickle, lime and grape. For
Swiss subjects three items were eliminated: dill pickle, lemon
and Cheddar cheese. Performance for each patient group was
calculated after excluding the relevant items.
The performance measure used was the percentage of
correct responses, calculated separately for each nostril. In
these, and all of the results to be reported, only those yielding
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M. Jones-Gotman et al.
Fig. 3 MRI scan coronal sections, at a level showing the amygdala, from the two patients in the amygdalohippocampectomy group
(Zurich) having the least and most extensive resection. Left: patient with right amygdalohippocampectomy; removal from amygdala,
hippocampus and parahippocampal gyrus were 25%, 20% and 20%, respectively (the resection lies within the region marked by the ‘1’
signs; the marks on this scan were placed for other measurements, not relevant to this paper). Right: patient with left
amygdalohippocampectomy; removals were 100% 82%, and 71%.
a P-value of ø0.05 are considered statistically significant.
Tukey HSD (honestly significant difference) tests were used
for post hoc comparisons except where otherwise stated.
An analysis of variance was carried out on these data, first
comparing only the control groups. The results confirm that
the groups did not differ [F(2,37) 5 1.56, P 5 0.22], and
there was no difference between the nostrils (F 5 0.63) nor
any significant interaction (F 5 0.77).
Performance of temporal-lobe resection patients
The data from all subjects were then entered into one analysis
of variance, comprising three factors: type of resection/
geographical location (Montreal, Dublin or Zurich), subject
group (normal control, left-side resection or right-side
resection), and nostril (left or right). The analysis revealed a
significant effect of geographical location/resection type
[F(2, 101) 5 15.5], showing overall poorer performance in
the Dublin population/neocorticectomy patients (mean 5
66.9) compared with each of the other two centres (Montreal
mean 5 83.3, Zurich mean 5 74.2), and as well poorer
performance in the Zurich population/amygdalohippocampectomy patients compared with the Montreal subjects.
There was also a significant effect of group [F(2, 101) 5
23.1], showing deficient performance in all patient groups,
whether left- or right-sided resection (mean left 5 69.8;
mean right 5 68.4), compared with the control groups
(mean 5 86.1). Left- and right-sided resections did not differ
from one another.
Finally, the most noteworthy finding was a significant
interaction of the side of excision with nostril [F(2,101) 5
13.0]. The interaction is depicted in Fig. 11, which shows
the performance of control groups, left-sided resection groups,
and right-sided resection groups, summed across type of
resection (or geographical sites). This last result reveals
deficits on both nostrils, compared with controls, in all patient
groups without respect to type of resection from the temporal
lobes, but in addition the patient groups showed significantly
more severe deficits ipsilateral to excision compared with
contralaterally. Thus, the performance of the left-excision
groups was significantly impaired in the left nostril compared
with the right, and that of the right-excision groups was
Odour identification
1851
Fig. 4 Anatomically based grid overlaid on eight coronal MRI slices, equally spaced between the anterior and posterior callosal planes
(see Methods). Each grid was divided into four sections: superomesial (SM), superolateral (SL), inferolateral (IL), and inferomesial (IM).
The percentage removal was calculated taking into account the total volume of temporal lobe structures within each section of the grid
(shaded area). Note that in this example the superomesial sections for slices 6–7 contain very little temporal lobe, and include mainly
portions of the temporal stem, part of the insula, and other extratemporal structures.
significantly impaired in the right nostril compared with the
left. Furthermore, the left nostril scores of the left-excision
groups were significantly lower than those of the right-
excision groups, and the right nostril scores of the rightexcision groups were significantly lower than those of the
left-excision groups.
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M. Jones-Gotman et al.
Fig. 7 Mean extent of removal from parahippocampal gyrus.
Format as in Fig. 5.
Fig. 5 Mean extent of removal from amygdala, estimated from
MRI scan measurements, for left and right resection groups at
each geographical location. Percentages shown are averaged from
the independent measurements made by FC and AMS.
Superimposed over the bars are filled circles representing the
removal for each individual in the group. This same format will
be used also for Figs 6–10.
Fig. 8 Mean extent of removal from anterior temporal neocortex
for the left and right resection groups in Dublin and Montreal
(there was no neocortical removal in the Zurich patients).
Otherwise, format is the same as described for Fig. 5.
Fig. 6 Mean extent of removal from hippocampus for each
resection group at each geographical location. As described for
Fig. 5.
There was no interaction of geographical location/type of
resection with group, and no three-way interaction of those
factors with nostril.
Analysis of performance relative to MRI data
Our original aim was to compare the effects of three distinct
types of surgical lesion on olfactory identification, but careful
study of the MRI scans revealed considerable overlap in the
tissue removed from Montreal and Dublin patients. Therefore,
in the analyses reported above we were unable to explore
the effect of type of surgical procedure fully. To deal with
this issue, we examined further the Dublin patients alone,
comparing the five with a relatively pure neocorticectomy
Fig. 9 Mean extent of removal from midbasal temporal
neocortex, for left and right resection groups in Dublin and
Montreal. As described for Fig. 5.
with those in whom significant encroachment had been
made on amygdala, hippocampus or parahippocampal gyrus.
Because of the small number of ‘pure’ cases, a formal
Odour identification
Fig. 10 Mean extent of removal from posterior basal temporal
neocortex, for left and right resection groups in Dublin and
Montreal. As described for Fig. 5.
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because of the differences among them in performance on
the task. Because of the nostril 3 group interaction in the
analysis of variance, separate analyses were performed for
each resection group, on the nostril ipsilateral to resection
only.
Thus, Pearson product-moment correlation coefficients
were computed across all patients, separately for each leftand right-side excision group. Each of the measures of
degree of excision (within the amygdala, hippocampus and
parahippocampal gyrus, and, for Dublin and Montreal cases,
the three neocortical measurements) was correlated against
performance on the ipsilateral nostril. No significant
relationships were found for any of these comparisons at the
0.01 level of significance, but there was a significant
correlation in the left neocorticectomy cases at P , 0.05
(two-tailed test); left nostril performance was negatively
correlated with extent of resection in the anterior temporal
measurement (r 5 –0.63).
Performance of the unoperated group
Fig. 11 Odour identification (UPSIT) scores: group 3 nostril
interactions, showing, separately for each nostril, mean percentage
of odours which were correctly identified by control subjects (n 5
40) and left- or right-resection patient groups (left, n 5 34; right,
n 5 36), summed across resection type (geographical location).
Left 5 resections from left temporal lobe. Right 5 resections
from right temporal lobe.
analysis could not be performed, but inspection of the means
showed performance above the mean of their group for the
three left neocorticectomy cases (77% left nostril, 59% group
mean left nostril; 69% right nostril, 61% group mean right
nostril), and performance lower than the mean of their group
for the two right neocorticectomy patients (50% left nostril,
65% group mean left nostril; 37% right nostril, 51% group
mean right nostril).
Correlations with resection size
To explore further any possible effect of lesion size and site
upon performance, correlational analyses were performed
relating test performance with extent of resection in each
medial and lateral temporal-lobe region. These analyses
were performed separately for each geographical population
Because deficits were found in all resection groups, a question
is raised as to whether or not impairment may already be
present in patients with an epileptic focus in the temporal
lobe, before any surgical procedure is carried out. It was not
possible to answer this question with the present sample,
which consisted of follow-up, seizure-free cases. However,
we were able to collect data from a separate sample of
Canadian patients with temporal-lobe epilepsy who were
good surgical candidates but not yet operated. The patients
were classified as having a left- or a right-sided focus based
on scalp EEG and clinical criteria (e.g. seizure pattern, and
neuroimaging when available). Their results on the UPSIT,
together with results from the Montreal normal control group,
were entered into an analysis of variance, which revealed a
significant effect of group [F(2, 46) 5 4.45] but not of nostril
(F 5 0.46), while the group 3 nostril interaction showed the
expected trend, approaching significance (F 5 2.9, P 5
0.06). Further analysis of the Group effect, using a Tukey
HSD post hoc test, showed that both patient groups were
impaired with respect to the normal control group (left-focus
mean 5 81.3, right-focus mean 5 75.3, control mean 5
89.0). The difference between left- and right-sided groups
did not reach significance.
Although in the analysis of variance, the group 3 nostril
interaction did not reach the conventional level of
significance, one might predict greater impairment on the
nostril ipsilateral to temporal-lobe focus than on the
contralateral nostril, based on the results observed in the
operated cases. To test this, we carried out planned
comparisons, which indeed showed significant impairment
on the right nostril compared with the left in the right-focus
group (t 5 8.3); however, there was no difference between
nostrils in the left-focus group (t 5 4.7) (Fig. 12).
Furthermore, only the left nostril was impaired with respect
to control subjects in the left-focus group (t 5 10.7, left
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M. Jones-Gotman et al.
Fig. 12 Odour identification (UPSIT) scores: group 3 nostril
interactions, in unoperated patients with temporal-lobe epilepsy
(Montreal only). Mean percentage of odours which were correctly
identified by each subject group (control, n 5 13; left TLE,
n 5 18; right TLE, n 5 18) is shown separately for each nostril.
TLE 5 temporal-lobe epilepsy.
nostril; t 5 4.85, right nostril), but in the right-focus group
both nostrils were impaired compared with controls (t 5
10.2, left nostril; t 5 17.35, right nostril).
Discussion
In this experiment, impaired odour identification was
observed in patients with resection from the anterior temporal
lobe, irrespective of whether mediobasal structures were
spared or whether temporal neocortex was spared.
Furthermore, the impairment was greatest in the nostril
ipsilateral to resection. This latter finding is consistent with
results from other monorhinal studies (Eskenazi et al., 1986;
Martinez et al., 1993), including our earlier results in a
monorhinal study of odour discrimination (Zatorre and JonesGotman, 1990). Thus the present findings extend and clarify
our previous odour identification results (Jones-Gotman and
Zatorre, 1988) in which mild but equal deficits were found
in both left and right temporal-lobe groups when those
patients were tested birhinally.
Although the performance of the control groups for the
three patient populations did not differ from one another,
there was an overall effect of geographical location (and no
interaction of geographical location with subject group),
despite the removal of apparent culture-specific items from
the Dublin and Zurich results. The Montreal population
performed best on this North American test, and it may be
that culture bias contributed to some extent to this result.
An unexpected finding in this study was that very few of
the neocorticectomy patients had a true sparing of the
amygdala. This was a disappointing discovery for the
purposes of the present experiment, but it is an important
one because it emphasizes the need to verify the site
and extent of surgical excisions with neuroimaging (Awad
et al., 1989).
The most common area of excision for all of the patients
should be in or near the amygdala. However, the
measurements showed that the extent of resection from both
the amygdala and the hippocampus tended to be greater in
the amygdalohippocampectomy patients, whereas the
excision size in the parahippocampal gyrus did not differ
significantly among the groups. Thus, the lack of functional
sparing in any group suggests that an intact parahippocampal
gyrus may be important for adequate performance on this
task. If so, it seems likely that resection in that region
interrupts function by disconnecting the normal interplay
between medial structures and temporal neocortex, without
pointing to a critical role for one region or the other in
olfaction. Furthermore, since patients with resection from
both temporal neocortex and medial structures did not do
worse than those with amygdalohippocampectomy, this
suggests that medial and lateral damage are not additive, and
perhaps that neither region is critical for olfaction.
A priori we predicted that the amygdala would prove
important in this task, not only because of our earlier findings
implicating the amygdala in odour memory (Jones-Gotman
and Zatorre, 1993), but because this structure has been shown
by many investigators (e.g. Bermudez-Rattoni et al., 1983;
Eichenbaum et al., 1986) to be important, in rats, in various
olfactory tasks. Functions affected are independent of primary
sensory abilities, which are intact in animals with amygdala
damage, but higher-order functions such as food aversion
learning (Bermudez-Rattoni et al., 1983) are affected. We
therefore anticipated good performance in our
neocorticectomy population, whose resections were reported
to spare amygdala as well as hippocampus. Because their
MRI scans showed encroachment on mediobasal structures
in most cases, we looked separately at the five cases whose
resections were strictly limited to temporal neocortex, and
found that the three left neocorticectomy patients did tend to
perform better than the mean of their group, while the
performance of the right neocorticectomy patients was
somewhat lower than the mean of their group. However, the
small number of subjects makes this observation
uninterpretable.
The failure to find normal performance in any operated
population raises the question of whether pre-existing damage
may exist in a region lying outside the areas excised in any
of the three surgical approaches. We therefore tested a
population of unoperated patients with temporal-lobe epilepsy
and found that they too were impaired on the UPSIT. Unlike
the operated patients, however, the left temporal-lobe epilepsy
patients were impaired only on the left nostril, whereas the
right temporal-lobe epilepsy patients were impaired on both.
While this result suggests that it may be true that a site
responsible for the observed odour identification deficits lies
outside the areas operated in our patients, it will not be
possible to know the effect of surgery on the pre-existing
deficit until this task is performed in the same patients before
and after operation.
Significant differences were observed in lesion size among
Odour identification
the groups: the amygdalohippocampectomy patients had no
resection from temporal neocortex, and they had significantly
greater resection from amygdala and from hippocampus than
did the neocorticectomy or anterior temporal-lobe resection
patients. Despite these differences in the surgical lesions, all
groups were impaired on the behavioural task, and we did
not find significant correlations between lesion size and task
performance. Thus it seems that lesion size did not contribute
to performance, and furthermore that the critical site
responsible for the impairment was also affected in the
unoperated patients.
This site may be in piriform cortex, which is active during
inhalation of odours (Zatorre et al., 1992). The known
connections between piriform cortex and the amygdala
(e.g. Luskin and Price, 1983a, b; Amaral and Price, 1984;
Aggleton, 1985; Moran et al., 1987), suggest that
periamygdaloid damage can cause deafferentation of the
amygdala, or disconnection between the amygdala and
piriform cortex; this disconnection may be sufficient to
interfere with normal odour identification in human subjects.
Furthermore, this interpretation implies that the piriform
cortex may function abnormally in patients with temporallobe epilepsy, suggesting a possible analogue, in humans, to
the highly epileptogenic area tempestas described in rats
(Piredda and Gale, 1985; Maggio et al., 1993; Gloor, 1997)
and, more recently, in monkeys (Gale and Dubach, 1993;
Gale et al., 1995; Gunderson et al., 1996).
Acknowledgements
We wish to thank Magali Brulot, Agnieszka Majdan and
Alan Witztum for invaluable help in this project, and J.
Phillips and M. G. Yasargil for allowing us to study their
patients. The work was supported by grant MT-10314 from
the Medical Research Council of Canada to M. Jones-Gotman
and R. J. Zatorre.
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Received February 28, 1997. Accepted May 22, 1997