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ORIGINAL ARTICLES

A Potential Role for Thalamocingulate Circuitry in


Human Maternal Behavior
Jeffrey P. Lorberbaum, John D. Newman, Amy R. Horwitz, Judy R. Dubno,
R. Bruce Lydiard, Mark B. Hamner, Daryl E. Bohning, and Mark S. George
Background: Little is known about the regional brain
basis of human maternal behavior. To understand this
better, we have been examining brain activity in mothers
listening to infant cries.
Methods: We measured functional Magnetic Resonance
Imaging brain activity in healthy, breastfeeding first-time
mothers with young infants while they listened to infant
cries, white noise control sounds, and a rest condition.
Based on the thalamocingulate theory of maternal behavior and pilot work, we hypothesized that the cingulate,
medial thalamus, medial prefrontal cortex, and right
orbitofrontal cortex would display more activity with
infant cries than with white noise (comparison 1) and
would uniquely activate with the cries, meaning that these
regions would display activity with cry minus rest but not
with white noise minus rest (comparison 2).
Results: In hypothesized regions, the group displayed
more activity in the medial thalamus, medial prefrontal
and right orbitofrontal cortices with both comparisons.
The anterior and posterior cingulate cortex displayed
more activity only with comparison 1. In non-hypothesized
brain regions, several other structures thought important
in rodent maternal behavior displayed activity with both
comparisons including the midbrain, hypothalamus, dorsal and ventral striatum, and vicinity of the lateral septal
region.
Conclusions: Our results partially support our hypotheses
and are generally consistent with neuroanatomical studies
of rodent maternal behavior. Biol Psychiatry 2002;51:
431 445 2002 Society of Biological Psychiatry
Key Words: Maternal behavior, infant crying, brain
imaging, functional magnetic resonance imaging, human,
auditory perception

From the Medical University of South Carolina (JPL, ARH, JRD, RBL, MBH,
DEB, MSG) and Ralph H. Johnson VA Medical Center (JPL, MBH, MSG),
Charleston, South Carolina, and National Institute of Child Health and Human
Development (JDN), Bethesda, Maryland.
Address reprint requests to J.P. Lorberbaum, M.D., Department of Psychiatry,
Medical University of South Carolina, Charleston, SC 29425
Received June 15, 2001; revised February 7, 2001; revised August 20, 2001;
accepted September 5, 2001.

2002 Society of Biological Psychiatry

Introduction

xtensive maternal behavior is critically important for


perpetuating the human species; however, surprisingly
little is known about the regional brain basis of maternal
behavior in humans. Such knowledge is crucial for understanding normal as well as abusive and neglectful mothering. Building on nonhuman mammalian investigations
into the brain basis of maternal behavior, we have been
using functional magnetic resonance imaging (fMRI) to
explore the brain basis of human maternal behavior.
Specifically, we have been examining fMRI brain activity
in human mothers while they listen to infant cries, which
are innate elicitors of maternal care-taking behavior.
Examining maternal response to infant cries is a potentially useful maternal behavior probe. First, in all studied
mammals, young infants emit a species-specific cry when
in distress, and mothers generally respond with care-taking
behavior (Bell and Ainsworth 1972; Bowlby 1969; Noirot
1972; Sewell 1970). For example, young rodents, monkeys, and humans cry when separated from their mothers,
and mothers generally respond with prompt expression of
maternal behavior, such as orienting, searching, and retrieving (Bell and Ainsworth 1972; Maestripieri 1995;
Noirot 1972; Sewell 1970). Second, a human mothers
response to infant cries appears to be an indicator of how
responsive she is to other infant cues (Bell and Ainsworth
1972). Third, maternal response to cries may help differentiate nurturing from maltreating mothers. Compared
with nonmaltreating mothers, maltreating mothers have
different physiologic responses to infant cries. They report
less empathetic and more aversive feelings toward a
crying infant (Frodi and Lamb 1980; Milner et al 1995).
Furthermore, a young infants inconsolable crying is often
the inciting event in cases of infanticide (Krugman 1983).
The work of Paul MacLean (MacLean 1990; personal
communications) initially motivated us to use maternal
brain response to infant crying as a way to investigate the
brain basis of human maternal behavior. MacLean (1990)
hypothesized that the brains thalamocingulate division
(the cingulate cortex and its connected medially located
thalamic nuclei) is important in mammalian motherinfant
attachment behavior such as infant crying and a mothers
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care-taking response. MacLean (1990) reported that the


thalamocingulate division is present in mammals but not
in lizardlike reptiles, who, unlike mammals, do not cry and
exhibit minimal parental care. Also, large anterior cingulate lesions (which include part of the overlying medial
prefrontal cortex) disrupt crying on separation in squirrel
monkeys (MacLean and Newman 1988). Furthermore,
anterior and posterior cingulate lesions impair maternal
behavior in rats and hamsters (MacLean 1990; Murphy et
al 1981; Slotnick 1967; Stamm 1955; Wilsoncroft 1963).
These cingulate lesions often included neighboring midline cortex and caused retrograde degeneration of medially
located thalamic nuclei such as the medial dorsal, medial
pulvinar, and anterior thalamic nuclei. In cingulate-lesioned mothers, the degree of maternal behavior impairment appears to strongly correlate with the degree of
accompanying anterior thalamic nuclei degeneration (Slotnick 1967; Slotnick and Nigrosh 1975), nuclei which
mainly project to the posterior cingulate cortex.1 In cingulate-lesioned mothers, motivation to care for pups appears to be present but mothering behavior seems disjointed and disorganized (Slotnick 1967; Stamm 1955;
Wilsoncroft 1963). For example, although mothers with
cingulate lesions try to retrieve separated pups, they often
drop them so that pups are scattered around the cage rather
than in the nest. These data suggest that the cingulate
cortex and thalamus may be involved in maternal behavior. It should be noted, however, that although in rats and
hamsters, cingulate lesions may substantially alter maternal behavior, some have failed to replicate the findings of
substantial maternal behavior impairment with cingulate
lesions in mice (Carlson and Thomas 1968; Slotnick and
Nigrosh 1975). Furthermore, in the rat, there is an abundant c-fos literature on forebrain sites labeled during
maternal behavior, and cingulate cortex labeling is generally not prominent with this technique (Lonstein et al
1998a).
To test MacLeans thalamocingulate hypothesis of maternal behavior in humans, we previously conducted a
small fMRI neuroimaging study of four physically healthy
mothers with a youngest child 3 weeks to 3.5 years old.
During the fMRI, mothers listened to recorded, standardized infant cries alternating with white noise control
sounds matching the cries in intensity and temporal
pattern. Mothers reported higher sadness and urges to help
1

According to Slotnick (personal communication), all cingulate lesions in his


studies either partly or fully transected the cingulum, a white matter fiber tract
that runs along the entire length of the cingulate cortex. In retrospect, Slotnick
feels that the retrograde anterior thalamic degeneration scores probably reflect
how effective the lesions were in transecting the cingulum and not reflect the
assumption in his papers that the behavioral deficits were due to destruction of
the cingulate cortex per se. This is because projections from the anterior
thalamic nuclei travel in the cingulum to their posterior cingulate targets so that
transecting the cingulum would cause retrograde degeneration in anterior
thalamic nuclei.

J.P. Lorberbaum et al

with the cries compared with the white noises. When we


averaged fMRI data over the four subjects, we found
statistically greater activity with infant crying than with
white noises in the subgenual level anterior cingulate (BA
24, 32), right mesial prefrontal cortex (BA 10), and right
orbitofrontal cortex (BA 47) all between Talairach axial
levels z 0 and 9 (Lorberbaum et al 1999). The anterior
cingulate activity is consistent with MacLeans thalamocingulate hypothesis of maternal behavior. Regarding the
right mesial prefrontal activation, most studies reporting
that cingulate lesions disrupt maternal behavior involve
animals that also had accompanying lesions of the neighboring mesial prefrontal cortex (Slotnick 1967; Stamm
1955; Wilsoncroft 1963). Regarding the orbitofrontal cortex activation, some researchers report that orbitofrontal
cortex lesions impair maternal behavior in free-ranging
Old World monkeys (Kling and Steklis 1976). More
generally, Stamm (1955) found that rats with large lateral
neocortical lesions (including the orbitofrontal cortex)
appeared less motivated in regard to maternal behavior. In
contrast, Murphy et al (1980) found that the neocortex was
not essential for normal maternal behavior in hamsters.
Regarding our right-sided findings, the right hemisphere is
thought to be preferentially involved in maternal behavior.
Most mothers (whether they are right- or left-handed) and
many higher primates carry their infants with their left arm
so that the infants head lies against the left breast (Salk
1960; Sieratzki and Woll 1996). Furthermore, human
mothers may be more likely to carry their infant on the left
than fathers and nonmothers (Horton 1995). Placing a
child on the left puts the infant in the mothers left visual
field with more direct communication to the right hemisphere (Sieratzki and Woll 1996). Consequently, several
researchers hypothesize that the right cerebral cortex may
have a specialized role in human social attachment (Henry
1993; Horton 1995; MacLean 1990; Sieratzki and Woll
1996).
Here, in a larger and more rigorously designed study
than our pilot, we hypothesize that the cingulate gyrus
(and its midline connected thalamic nuclei) as well as
regions within the right mesial and orbitofrontal prefrontal
cortex will again be more active when mothers listen to
infant cries compared to white noise control sounds. We
also hypothesize that these same brain regions would
uniquely activate with the cries. That is, these regions
would not only be more active with cries than with control
sounds but they would also be active with cries but not
with control sounds compared with a low arousal rest
condition.
Although our a priori hypotheses focuses on the cingulate, thalamus, and right prefrontal cortex, other structures
have been implicated in mammalian maternal behavior.
Extensive data consistently implicate the medial preoptic

Thalamocingulate Circuitry and Maternal Behavior

area (MPOA) and the nearby ventral bed of the stria


terminalis (VBNST) as critical facilitators of rodent maternal behavior (Numan 1974; Numan et al 1977, 1985,
1988, 1990; Numan and Numan 1996). Also implicated in
rodent maternal behavior are the following:
1. MPOA/VBNST midbrain projections to the hypothalamus, ventral tegmental area (VTA), and substantia nigra/retrorubral fields (Factor et al 1993;
Hansen and Kohler 1984; Numan et al 1985; Numan
and Nagle 1983; Numan and Smith 1984).
2. The mesolimbic/mesocortical and nigrostriatal dopaminergic approach behavior pathways that emanate from the VTA and substantia nigra/retrorubral
fields, respectively (Hansen 1994). This is interesting because approach behavior may be necessary for
retrieving separated pups and foraging during nest
building (Numan and Nagle 1983; Panksepp 1998).
3. MPOA midbrain projections to the central gray, a
region known to be involved in defensive behavior.
These projections may be involved in increasing
maternal aggressiveness toward intruders (Lonstein
and Stern 1997; Lonstein et al 1998b) or preventing
a mothers aggression toward pups (Numan 1997).
4. Limbic structures with MPOA/VBNST connections
such as the septal region and amygdala. Rats and
mice with septal region lesions display poor nest
building, display disorganized retrieval responses
similar to that seen with cingulate lesions, and
appear more prone to committing infanticide (Flannelly 1986; Novakova 1993; Slotnick and Nigrosh
1975). Some evidence suggests that amygdala lesions inhibit maternal behavior (Fleming et al 1979,
1983; Numan 1994; Numan et al 1993; Numan and
Sheehan 1997) whereas other evidence suggests that
such lesions facilitate maternal behavior (Kling and
Steklis 1976).

Methods and Materials


Recruitment
We recruited first-time mothers with infants aged 4 to 8 weeks
through newspapers, e-mail, and flyers distributed around the
university community. We screened potential subjects by phone.

Initial Visit
We informed subjects that our goal was to identify brain regions
that activate when new mothers listen to different sounds and that
this information would help us have a better understanding of
mothering behavior. Subjects were not specifically informed of
the sounds they would be hearing, including the infant cries.
After giving informed consent, subjects underwent structured
clinical interviews for DSM-IV Axis I and II disorders (First et

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2002;51:431 445

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al 1997; Gibbon 1997) as well as physical and neurologic


examinations. Subjects also received a urine pregnancy test.
Subjects filled out the Annett Handedness scale (Annett 1970) to
assess handedness, the Cloninger Temperament and Character
Inventory (Cloninger 1994; Cloninger et al 1993) to assess their
own temperament, and the Carey Early Infant Temperament
Questionnaire (Medoff-Cooper et al 1993) to assess their infants
temperament.

Inclusion and Exclusion


For inclusion, subjects had to be biological, breastfeeding,
first-time mothers aged 18 to 45 with full-term healthy infants
aged 4 to 8 weeks old. Subjects had to be right-handed (Annett
1970) and physically healthy. They had to have no history of
DSM-IV Axis I or II psychiatric disease (First et al 1997; Gibbon
1997), significant neurologic illness, sexual or physical abuse, or
Child Protective Services involvement either in their immediate
family of origin or with their current family. Additionally,
subjects could not be pregnant, be on oral contraceptives or
psychotropic medication for at least 5 half-lives, or have MRI
contraindications (such as implanted metallic objects or severe
claustrophobia).

MRI Scanning Parameters


We assessed regional brain function with Blood Oxygen Level
Dependent fMRI (BOLD-fMRI) on a Picker Edge 1.5T MRI
scanner equipped with high performance whole-body gradients.
Subjects were positioned in the scanner with stereo headphones
without earplugs. Head movement was restrained using inflatable
cushions. We acquired T2*-weighted echoplanar BOLD functional images (TE 40; TR 3000; FOV 27.0 27.0 cm; in-plane
resolution 2.109 2.109 mm; through-plane resolution 7 mm).
We obtained fifteen 5-mm-thick coronal slices spaced 2 mm
apart, angled 90 to the anterior commissureposterior commissure line, and centered at the most posterior edge of the corpus
callosums anterior genu. This permitted viewing of the entire
anterior cingulate and part of the posterior cingulate (see field of
view in Figure 1: Panel C). Of note, this location was approximately 12 mm anterior to slice placement in our previous study
(Lorberbaum et al 1999), because in that study we found anterior
cingulate activity (not posterior cingulate activity) and wanted to
obtain more complete viewing of the prefrontal cortex.

Functional MRI Paradigm


CRY STIMULI. Two cry stimuli were used. The two cry
stimuli were recorded from different infants in Bryan and
Newman (1988). Each was a 30-sec natural cry sample recorded
from a 3-day-old, full-term, human infant being weighed 1 hour
after a feeding. One cry (NIH Cry 16) was from a low-risk baby
not included in Bryan and Newmans final paper; the other cry
(labeled HF1 in Bryan and Newman (1988) was from a high-risk
infant.
CONTROL NOISE STIMULI. We made each crys control
noise by replacing cry bursts with intensity-matched white noise

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bursts to simulate the crys temporal pattern (Cool Edit Pro


Version 1.2, Syntrillium Software, Phoenix, AZ).
PARADIGM. During an 8-min (160-scan) BOLD-fMRI session, subjects used headphones to hear recorded 30-sec infant
cries alternating with 30-sec control noises. These two stimuli
were always separated by a 30-sec rest period during which only
background scanner noise could be heard. The cry and control
noise stimuli sounds were delivered to their headphones with
Macintosh-based Superlab software (Cedrus, Rockville, MD).
Subjects were instructed to close their eyes and were told, You
will be hearing a series of sounds played through the headphones.
I just want you to listen to them. Ill ask you some questions
about them after the task is done. Odd-numbered subjects heard
four consecutive trials of the following 120-sec cycle: 30-sec
rest, 30-sec control noise, 30-sec rest, 30-sec cry. To control for
order effects, even-numbered subjects heard four cycles of rest,
cry, rest, control noise. Subjects heard the NIH infant cry with its
matched white noise control sound in two cycles, and the HF1
infant cry with its matched white noise control sound in the other
2 cycles. These four cycles were played in a random order.
POSTSCAN EMOTIONAL RATINGS. After imaging, subjects retrospectively rated their emotional reactions (anxiety,
sadness, annoyance, anger, frustration, and an urge to help) to the
cries, control noises, and background scanner noises on average
from 0 (lowest) to 100 (highest) on visual analog scales.

5. Temporal filtering: The data were filtered using a Butterworth low frequency filter removing fMRI intensity patterns greater than twice the cycle lengths period (240 sec).
6. Statistical analysis: Using the SPM96 statistics function
and then MEDxs image calculator, the individual subject
fMRI data were statistically analyzed to generate unthresholded z maps for control noise minus rest, cry minus rest,
cry minus control noise, and control noise minus cry z
maps. These z maps contained a z score for each insidethe-brain voxel, whether the z score was positive, negative,
large, or small. In generating these z maps, we used the
SPM96 options for a delayed boxcar model, temporal
smoothing, and an uncorrected F threshold (UFp) of
0.999.
GENERATING GROUP STATISTICAL DATA USING A RANDOM EFFECTS ANALYSIS AND THEN A CLUSTER ANALY-

Here, we only discuss generation of group cry minus


control noise data; however, we used analogous procedures to
generate the group data for the other comparisons.
We used a random effects analysis to combine the mothers
individual cry minus control noise z maps generated by step (6)
to make a group z map for the mothers. We then performed a
cluster analysis (Friston et al 1994) on the resulting group z map
using a z map threshold of z 1.96 and cluster statistical weight
(spatial extent threshold) of p .05. We also found local
maxima on these group cluster maps.
SIS.

FINDING BRAIN REGIONS FOR THE GROUP UNIQUELY

Data Analysis
We performed all data analysis on Sun SPARCstation workstations (Sun Microsystems, Mountain View, CA) using MEDx
3.2/SPM96 (Sensor Systems, Sterling, VA; Frackowiak et al
1997).
INDIVIDUAL SUBJECT FMRI DATA ANALYSIS. Our goal
here was to generate unthresholded z maps comparing control
noise versus rest, cry versus rest, and cry versus control noise for
each subject. To accomplish this, each subjects functional MRI
data were taken through the following steps:

1. Motion detection and correction: The data were motioncorrected to less than 2 2 2 mm in all planes using
Automatic Image Registration (Woods et al 1992). After
motion correction, all subjects had 1.4-mm movement
in all planes.
2. Spatial normalization: The data were then transformed into
Talairach space with output voxel dimensions 3 3 3
mm and a coronal bounding box of y 42 to 70 to
account for the fact that we did not obtain imaging data in
posterior brain regions.
3. Spatial smoothing: The data were then spatially smoothed
using a 6 6 6 mm gaussian kernel.
4. Intensity masking and normalization: Each image volume
was then intensity masked using a 35% of maximum
intensity inclusion threshold and intensity normalized so
that its mean signal intensity was 1000.

We only
discuss how we generated the uniquely activated by cries group
statistical map. An analogous method was used to generate the
uniquely activated by control sounds statistical map.
Our goal here was to find regions that were active with cries
but not with control noises and that were also statistically more
active with the cries than the control noises. To do this, we first
created a mask of voxels which had a z score 1.96 on the group
cry minus rest z map and 1.96 on the group control noise
minus rest z map. In this masked active with cry minus rest, not
active with control noise minus rest region, we then performed
a cluster analysis on the group cry minus control noise z map
using a z map threshold of z 1.96 and cluster statistical weight
of p .05. We also found local maxima on this uniquely
activated by cries group cluster map.
ACTIVATED BY CRIES AND CONTROL NOISES.

Results
Subtests and Ratings
Usable fMRI data existed on 10 of 11 mothers. One data
set was accidentally acquired with a different MRI field of
view from the others and was discarded. All the data
below refer to the 10 included subjects. Group demographics as well as Maternal and Infant Temperament Ratings
are displayed in Table 1. Mothers were 30.55 4.66 years
old, and their infants were 6.18 1.1 weeks old. Nine
mothers were married; the 10th mother was abandoned by
her husband during her pregnancy.

Thalamocingulate Circuitry and Maternal Behavior

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Table 1. Group (n 10) Demographics and Temperament


Ratings (Means Standard Deviations Noted)
Demographics
Mothers age
Infants age
No. married mothers
Ethnicity
Caucasian
Asian American
Latin American
Maternal Temperament (CTCI raw scores)
Novelty seeking
Harm avoidance
Reward dependence
Reward dependence attachment subscale
Persistence
Goal directedness
Cooperativity
Transcendence
Infant Temperament (CEIT raw scores as
rated by mothers)
Adaptability
Mood
Activity
First reaction
Strength of Response
Distractibility
Persistence
Sensory reactivity
Daily cycles
Overall manageability

30.55 4.66 years


6.18 1.1 weeks
9
8
1
1
20.3 5.1
9.6 5.0
18.3 2.9
6.8 1.4
4.7 1.8
38.3 10.1
39.6 1.9
12.0 4.9
1.00 .82
.09 .83
.05 .80
.58 .87
.03 1.19
.65 1.03
.33 .95
.12 1.36
.15 1.13
1.90 1.20

CTCI, Cloninger Temperament and Character Inventory; CEIT, Carey Early


Infant Temperament.

Mothers emotional ratings to the infant cry, control


noise, and rest (scanner noise only) conditions are displayed in Table 2. As shown in the table, the cries (relative
to the rest and control noise conditions) produced significantly more self-rated sadness and urges to help as
well as a trend for more self-rated anxiety. The control

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noises produced significantly more annoyance than did


the cries and more anger than did the rest condition.

Brain Regions Visualized


We acquired data coronally and did not image posterior
brain regions (Figures 1 and 2). We analyzed 31,219
voxels, all within the Talairach y axis (coronal) direction
bounding box y 30 to 66 mm. This means that in
regions of potential interest, there was some data missing
in 6 to 9 mm of the anteriormost frontal cortex below axial
level z 20, posterior brain stem (including the medial
geniculate and inferior colliculi important for auditory
processing and posterior central gray, which is potentially
important in maternal behavior), posterior thalamus, posterior hippocampus, posterior cingulate, primary auditory
cortex (BA 41, 42), fusiform gyrus (a region found
important in social signal [i.e., face] detection; Haxby et al
1994), and the entire cerebellum. Additionally, due to
airtissue artifact, there were many missing datapoints
in the orbitofrontal cortex below z 9 (i.e., below the
subgenual cingulate) especially medially, anterior temporal poles below z 24 (i.e., below the amygdala), and
brain stem below z 36 (i.e., below the inferior
pons/superior medulla). The stippled region on the sagittal
slices in Figures 1 and 2 indicate regions partially visible
due to airtissue artifact.
Group fMRI data are displayed in Table 3 and Figures
1 and 2. In this section, we first present findings from our
two main comparisons of interest, namely, regions activated by cries minus control noises (Table 3, column 4)
and the subset of this comparison uniquely activated with
the cries (Table 3, column 5). We then show the results of
other comparisons: cry minus rest (Table 3, column 3),
control noise minus rest (Table 3, column 2), control noise
minus cry, and uniquely activated with control noise that
helped us better understand our main two comparisons of
interest.

Table 2. Mothers Retrospective Average Emotional Ratings during the Infant Cry Imaging Paradigm (Means Standard
Deviations Noted)

Emotional ratings

Control noises
(0 to 100)

Sadness
Anxiety
Anger
Frustration
Annoyance
Urge to help

4.8 5.0
31.5 28.4
5.8 5.4
17.9 28.5
35.5 25.8
7.9 11.6

5.2 4.9
35.1 29.3
13.0 10.3
24.7 27.2
43.2 29.9
14.8 26.2

Trend difference at p .06 level on a two-tailed paired t test.


Trend difference at p .11 level on a two-tailed paired t test.
Significantly different at greater than p .05 level on a two-tailed paired t test.

a
b
c

Emotion

Scanner noises
during rest
(0 to 100)

Cries
(0 to 100)

Control noises
minus scanner
noises with rest
(100 to 100)

Cries minus
scanner noises
with rest
(100 to 100)

Cries minus
control noises
(100 to 100)

55.6 26.5
58.1 17.6
10.6 13.1
27.4 30.0
24.4 21.2
84.8 14.4

.4 6.9
3.5 20.3
7.2 8.7c
6.8 14.2
7.7 24.5
6.9 15.5

50.9 28.7c
26.6 40.0a
4.8 13.6
9.6 28.1
11.9 29.5
76.9 16.1c

50.5 24.1c
23.1 41.2b
2.4 8.5
2.7 28.1
19.6 24.2c
70.0 26.0c

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Figure 1. Brain regions more active when new mothers listen to infant cries than when they listen to white noise control sounds. This
figure displays active regions with cry minus control sounds (z 1.96; cluster extent threshold p .05) superimposed on high
resolution SPM96 structural magnetic resonance imaging template axial, coronal, and sagittal slices. Yellow is more active than red.
Regions of activation included: 1) midbrain regions in the vicinity of the hypothalamus/mammillary bodies, bilateral substantia
nigra/retrorubral fields, and central gray extending to the ventral tegmental area (axial slice); the pontine gray region is also active but
is not displayed); 2) ventral striatal/basal forebrain regions in the vicinity of the caudate/septal region/globus pallidus/nucleus
accumbens (NA)/bed of the stria terminalis (BNST); (coronal slice); the right putamen and more superior caudate is also active but is
not shown; the medial preoptic area (MPOA)/ventral bed nucleus of the stria terminalis (VBNST) region is not active but is labeled
in the coronal slice for comparison of approximate spatial relationship between the area of activation and this important maternal
behavior region in rodents; 3) anterior and posterior cingulate cortex, mesial prefrontal cortex, and medial thalamus (sagittal slice); 4)
paralimbic belt regions (right orbitofrontal-insula-temporal polar cortices); (axial slice); 5) a small portion of the right inferior part of
the dorsolateral prefrontal cortex (an extension of the right paralimbic belt cluster; not shown); 6) temporal lobe auditory and
association cortices (right left) (axial slice; right-sided activity shown only). As displayed on axial and sagittal slices, posterior brain
regions were not imaged. Furthermore, portions of the inferior orbitofrontal and anterior temporal regions were not fully visible due
to airtissue artifact (stippled region in sagittal slice).

Group fMRI Data


ACTIVE

REGIONS

WITH

CRY

MINUS

CONTROL

Working from the top of Table 3 downward,


active regions with cry minus control noise included:

NOISE.

1. Several midbrain/brain stem regions in the vicinity


of the hypothalamus/mammillary bodies, substantia
nigra/retrorubral fields/peripeduncular nuclei region, midbrain central gray/VTA, and pontine gray
(Figure 1, Panel A);

2. Medial thalamic nuclei in the vicinity of the anterior,


midline, dorsomedial, and medial pulvinar nuclei
(Figure 1, panel C);
3. The striatums right putamen and caudate (with a
medial region that could be caudate, nucleus accumbens, globus pallidus, septal region, or bed nucleus
of the stria terminalis; Figure 1, Panel B);
4. Supracallosal posterior (BA 23, 31) and anterior
(BA 24, 32) cingulate cortex clusters as well as a
pregenual anterior cingulate (BA 24 32)/mesial

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Figure 2. Regions uniquely active when new mothers listen to infant cries. This figure displays regions uniquely active with cries
superimposed on the same high-resolution SPM96 structural magnetic resonance imaging template shown in the other figure. By
uniquely active with cries, we mean regions that are active with cry minus rest, not active with control noise minus rest, and additionally
more active with cries than with control noises. Regions of activation here are a subset of cry minus control noise active regions (Figure
1). Yellow is more active than red. Activations are quite similar to that of cry minus control noise with a few notable exceptions: 1) the
midbrains substantia nigra/retrorubral fields activated is no longer bilateral but is restricted to the left (axial slice); although there
appears to be no activity in the central gray/VTA region in the axial slice, there is still activity in this region just not at this axial level;
2) the cingulate cortex is no longer active and the cingulate/mesial prefrontal cortex cluster activation is now restricted to a small
pregenual mesial prefrontal cortex region (sagittal slice); notice that there is no longer mesial prefrontal/medial orbitofrontal subgenual
level activity (axial slice); 3) the right insula is no longer active, but there is still activity in the lateral orbitofrontal andtemporal polar
cortices (axial slice). Regions not imaged due to our chosen field of view and airtissue artifact are labeled similarly to Figure 1.

prefrontal cortex (BA 8, 9, 10) cluster that extends


downward to the subgenual level into the inferior
mesial prefrontal (BA 10)/superior midline orbitofrontal cortex (BA 11; Figure 1, Panel C); and
5. The right paralimbic belts orbitfrontal (BA 11, 47),
temporal polar (BA 38), and insular cortices (Figure
1, Panel A);2
6. A small portion of the right paralimbic belt cluster
extending beyond paralimbic cortex and into the
lateral inferior dorsolateral prefrontal cortex (BA
45);

We define the posterior orbitofrontal cortex, temporal pole, and insula as the
paralimbic belt. These three structures are adjacent and histologically similar
(Mesulam 2000). They participate in linking cognition with emotion and
visceral states (Mesulam 2000) and are sometimes difficult to resolve separately in group fMRI studies. Mesulum (2000) referred to these three structures
as the olfactocentric paralimbic belt. The meaning of our paralimbic belt is the
same as Mesulams olfactocentric paralimbic belt.

7. Auditory and audiovisual association cortices bilaterally but with more activity on the right (namely,
BA 22 bilaterally and BA 20, 21, and 42 on the
right; Figure 1; Panel A).
ACTIVATIONS UNIQUE TO CRY. Activations unique
to cry were generally similar to those of cry minus control
noise (Figure 2 vs. Figure 1) with a few notable exceptions. There was no longer any cingulate activation and the
mesial prefrontal/anterior cingulate cluster active with cry
minus control noise was reduced to a small pregenual
mesial prefrontal cortex cluster (BA 9, 10) anterior to BA
32 from Talairach axial level z 2133 (see Table 1 and
Figure 1 vs. Figure 2: Panel C). In the right paralimbic
belt, activity was confined to the temporal polar (BA
38)/lateral orbitofrontal (BA 47) cortex region and there
was no longer any insula or medial orbitofrontal BA 11
activation (Figure 2: Panel A).

438

J.P. Lorberbaum et al

BIOL PSYCHIATRY
2002;51:431 445

Table 3. Brain Regions Active in Group Control Noise Minus Rest (CNMR), Cry Minus Rest (CMR), Cry Minus Control Noise
(CMCN), and Uniquely Active with Cry (C)
Local maxima from: cry minus rest, control noise minus rest, cry
minus control noise, and uniquely active with cry cluster maps

CNMR
Cluster Map

Talairach Points (x, y, z) and Structure


Names Are Listed
Brainstem/Midbrain
0 6 6
0 24 9
15 21 12
12 18 12
0 12 15
9 10 21
Thalamus
9 3 15
6 9

12

3 27
0 9

9
3

6 18
Striatum
18
9
24 12
6
6

0
12
12
6

18
6 3
18 9 6
15 18 6
27 12
3
12 15 3
Medial temporal cortex
18
0 15
Cingulate
18
3 42
3 18 39
6 15 36
18 18 33
0 6 30
0 24 30
21 9 30
6 21 27
21 36 15
21 36
3
3 24 9
9 18 9
21 18 12
Mesial Prefrontal Cortex
15 18 60
12 18 57
12 30 54
9 12 51
6 39 48
21 42 45

CMR
Cluster Map

CMCN
Cluster Map

C Cluster
Map

z score of nearest active Talairach point within a


resolution (resel) unit listed if one exists

Medial Midbrain Region


(Hypothalamus/Mammillary Bodies)
Medial Midbrain Region
(Central gray/VTA Region)
L. Lateral Midbrain Region
(Subst. Nigra/Retrorubral Fields)
R. Lateral Midbrain Region
(Subst. Nigra/Retrorubral Fields)
Medial Midbrain Region
(Hypothalamus/ Mammillary Bodies)
R. Pontine Gray Region
Anterior Nuc./Caudate/
Dorsal Septal Region
Dorsomedial Nuc./Anterior
Nuc./Dorsal Septal Region
Medial Pulvinar Nuc. Region
Dorsomedial Nuc./Anterior
Nuc./Hypothalamus Region
Dorsomedial Nuc. Region

2.85

3.12

3.12

2.50

2.54

2.14

3.15

2.33

3.14

3.14

2.97

2.15

2.15

2.80

2.01

2.01

2.82

3.67

2.86

2.86

2.35
2.71

2.92
2.92

2.92
2.92

3.17

2.84

2.84

R. Caudate/Putamen
R. Putamen/Globus Pallidus
R.Caudate/Ventral Septal/Nuc.
accumbens/Globus Pallidus/Bed Nuc.
Stria Terminalis Region
R. Putamen/Caudate
R. Globus Pallidus/Amygdala
R. Putamen/Insula
L. Putamen/Insula
L. Caudate/Nuc. Accumbens Region

2.45
2.33

2.55
2.02
2.47

2.47

3.06

2.47

2.24

2.17
2.06
2.79
2.05
3.34

4.04
2.57
2.40

2.06

2.06

R. Amygdala

3.31

2.25

Ant. Cingulate G. BA 24/32


Post. Cingulate G. BA 24/31
Ant. Cingulate G. BA 32
Ant. Cingulate G. BA 24/32
Ant. Cingulate G. BA 24
Ant. Cingulate G. BA 32
Ant. Cingulate G. BA 24
Post. cingulate G. BA 23
Ant. Cingulate G. BA 24/32
Ant. Cingulate G. BA 24
Ant. Cingulate G. BA 32
Ant. Cingulate G. BA 25/32
Subcallosal G. BA 25

3.28

2.77

4.03
2.13
2.08
3.02
3.14
2.73
3.10

2.60

2.11
2.81

3.67
3.09

4.00

Superior
Superior
Superior
Superior
Superior
Superior

3.11
2.08
2.55
3.15

3.09

3.05
2.17
2.12
2.05

2.42

Frontal
Frontal
Frontal
Frontal
Frontal
Frontal

G.
G.
G.
G.
G.
G.

BA
BA
BA
BA
BA
BA

6
6
6/8
6
8
8

Thalamocingulate Circuitry and Maternal Behavior

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2002;51:431 445

439

Table 3. Continued
Local maxima from: cry minus rest, control noise minus rest, cry
minus control noise, and uniquely active with cry cluster maps

CNMR
Cluster Map

Talairach Points (x, y, z) and Structure Names Are Listed


18 24
18 48
18 27
3 48
9 57
9 60
15 45
6 57
18 54
18 57
3 51
21 42
3 60
Orbitofrontal
27 21
24 27
33 45
51 15

42
Superior Frontal G. BA 8
39
Superior Frontal G. BA 8
33
Medial Frontal G. BA 8/9
33
Superior Frontal G. BA 9
27
Superior Frontal G. BA 9/10
27
Superior Frontal G. BA 9/10
24
Medial Frontal G. BA 10
21
Medial Frontal G. BA 9/10
15
Superior Frontal G. BA 10
15
Superior Frontal G. BA 10
3
Medial Frontal G. BA 10
3
Medial Frontal G. BA 10
9
Superior Frontal G. BA 10
Cortex-Temporal Pole-Insula
18
R. Insula
0
R. Insula
3
R. Middle Frontal G. BA 10/47
3
R. Inferior Frontal G. BA 47/
Superior Temporal G. BA 22
39 57 3
R. Middle Frontal G. BA 10
30 24 9
R. Inferior Frontal G. BA 47/Insula
54 39 9
R. Inferior Frontal G. BA 47
36 54 12
R. Middle Frontal G. BA 11
15 51 12
R. Superior Frontal G. BA 11
63
9 12
R. Superior Temporal G. BA 38
45 39 15
R. Middle Frontal G. BA 11
51 27 18
R. Inferior Frontal G. BA 47/
Superior Temporal G. BA 38
36 21 24
R. Inferior Frontal G. BA 47/
Superior Temporal G. BA 38
48 12 24
R. Superior Temporal G. BA 38
27 12 15
L. Insula
36 39 12
L. Middle Frontal G. BA 10
36 54
6
L. Middle Frontal G. BA 10
27 27 3
L. Inferior Frontal G. BA 47
39 24 3
L. Insula
39 39 6
L. Middle Frontal G. BA 47
36 51 6
L. Middle Frontal G. BA 10
51
3 9
L. Superior Temporal G. BA 38
27 48 15
L. Superior Frontal G. BA 11
21 36 18
L. Middle Frontal G. BA 11
45
9 21
L. Superior Temporal G. BA 38
Dorsolateral Prefrontal Cortex
45 12 51
R. Middle Frontal G. BA 6
54
9 42
R. Middle Frontal G. BA 6/8
45 21 39
R. Middle Frontal G. BA 8
39
9 33
R. Middle Frontal G. BA 9
51 30 27
R. Middle Frontal G. BA 9
45
3 27
R. Inferior Frontal G. BA 9
51 15 24
R. Inferior Frontal G. BA 44
39 33 21
R. Middle Frontal G. BA 46
33 21 21
R. Inferior Frontal G. BA 45
33 42 15
R. Middle Frontal G. BA 46
54 21 12
R. Inferior Frontal G. BA 44/45
51 36 12
R. Inferior Frontal G. BA 46
42 30
6
R. Inferior Frontal G. BA 45

CMR
Cluster Map

CMCN
Cluster Map

C Cluster
Map

z score of nearest active Talairach point within


a resolution (resel) unit listed if one exists
3.13
2.45
2.94

2.37

3.24

2.59

3.40

1.98
2.24
3.50
2.26
2.44
2.38

2.26

2.01

2.77
2.89
3.01

3.86
2.37

3.07

3.35

2.29
2.89
3.01

3.86

2.28

2.31

3.15
3.25
2.37

3.88

3.70

2.90

3.05
2.85
2.77
2.63
2.65
2.44

2.33
2.17
2.72
2.84

2.46
4.02
3.56

2.15
2.08

2.19
2.04
2.14
2.28

2.12

2.04

2.20

3.31

3.45

2.15
2.57
3.40
3.39
3.47
3.26
3.39
3.21
2.91
2.59
3.31
3.04

2.95

3.03

2.62

2.54

2.02
2.75
2.57
2.66
2.79
2.12
4.09
4.98
3.69
3.12
2.16
2.94
2.56

2.11
2.62
2.92
4.35
3.80
3.54
2.22
3.12
3.09
2.04
4.18
3.24
2.45

2.90

2.90

440

J.P. Lorberbaum et al

BIOL PSYCHIATRY
2002;51:431 445

Table 3. Continued
Local maxima from: cry minus rest, control noise minus rest, cry
minus control noise, and uniquely active with cry cluster maps

CNMR
Cluster Map

6
R. Inferior Frontal G. BA 45
3
R. Inferior Frontal G. BA 44
48
L. Middle Frontal G. BA 8
27
L. Middle Frontal G. BA 9
3
L. Inferior Frontal G. BA 45
Association Cortices
9
R. Superior Temporal G. BA 22/42
(Posterior Superior Temporal Sulcus)
66 27
6
R. Superior Temporal G. BA 22/42
(Posterior Superior Temporal Sulcus)
63 21
0
R. Superior Temporal G. BA 22/21
(Central Superior Temporal Sulcus)
57 21 9
R. Middle Temporal G. BA 21
(Central Superior Temporal Sulcus)
66 12 3
R. Middle Temporal G. BA 21
(Central Superior Temporal Sulcus)
66
0
0
R. Superior Temporal G. BA 22
(Anterior Superior Temporal Sulcus)
57 3 6
R. Middle Temporal G. BA 21
(Anterior Superior Temporal Sulcus)
51 6 12
R. Middle Temporal G. BA 21
(Anterior Superior Temporal Sulcus)
54
9 18
R. Middle Temporal G. BA 21/38
(Anterior Superior Temporal Sulcus)
63 9 12
R. Superior Temporal G. BA 42/22
66 24 9
R. Middle Temporal G. BA 21
51 27 12
R. Middle Temporal G. BA 20/21
60 3 15
R. Inferior Temporal G. BA 21
48 21 15
R. Middle Temporal G. BA 20
39 18 21
R. Inferior Temporal G. BA 20
51 6 33
R. Inferior Temporal G. BA 20
57 21
3
L. Superior Temporal G. BA 22
(Central Superior Temporal Sulcus)
45 18
3
L. Superior Temporal G. BA 22
39 9 15
L. Middle Temporal G. BA 20/21
42
3 21
L. Middle Temporal G. BA 21
Somatosensory Cortex
36 18 27
R. Postcentral G. BA 3/1/2

CMCN
Cluster Map

C Cluster
Map

z score of nearest active Talairach point within


a resolution (resel) unit listed if one exists

Talairach Points (x, y, z) and Structure Names Are Listed


60 18
51 45
36 21
30 18
33 33
Auditory and
54 30

CMR
Cluster Map

2.89
2.07
3.01
3.06
3.04

2.13
3.81

3.92

2.17

3.13

4.60

3.95

3.09

1.97

2.39

1.98

2.39

2.39

2.20

3.82

3.54

3.54

2.02

2.45

2.23

2.23

2.11

2.69

2.97

2.97

2.95

2.06

1.99

1.99

2.97

3.29

2.28

3.27
2.06
2.03
2.03
2.16
2.87
2.89
3.83

2.12
2.45
2.50
2.56
3.11

2.36

1.98
2.82
2.99
2.63
2.57

1.97

2.82

2.45

2.05

2.51
3.31
2.45

4.44
2.67
2.57

3.09

2.20

CNMR, control minus noise rest; Ant, anterior; Post, posterior; G, gyrus; L, left; R, right; Nuc., nucleus; BA, Broadmans area; VTA, ventral tegmental area; CMR, cry
minus rest; CMCN, cry minus control noise.

Findings of Interest in Other Contrasts


RELATIONSHIP BETWEEN REGIONS UNIQUELY AC-

area), unique activity with the cries existed in these brain


divisions except for the cingulate cortex.

TIVE WITH CRIES AND REGIONS ACTIVE WITH CON-

First, unlike the uniquely


active with cries comparison, control noise minus rest
produced no activity in the brain stem, midbrain, or
thalamus. Second, regarding other brain divisions listed in
Table 3 that were uniquely active with cries, they were
generally active as well with control noise minus rest;
however, due to some geographic differences between cry
minus rest and control noise minus rest within these
divisions (sometimes even within the same Brodmann
TROL NOISE MINUS REST.

AMYGDALA. The right amygdala region was active


with cry minus rest and control noise minus rest, but not
with cry minus control noise.
HEMISPHERIC LATERALITY. The ratio of right
hemisphere to total number of active voxels was 2072/
3156 (66%) in control noise minus rest, 2690/3054 (88%)
in cry minus rest, 979/1186 (83%) in cry minus control
noise, and 401/467 (86%) in uniquely active with cry. The

Thalamocingulate Circuitry and Maternal Behavior

laterality differences in these comparisons were mainly a


result of findings in the lateral prefrontal cortex (including
the paralimbic belt) and temporal lobe auditory/association cortex, where cry minus control noise and uniquely
activated by cries comparisons were completely confined
to the right hemisphere, cry minus rest was mostly
right-sided, and control noise minus rest displayed generally bilateral activation.
CONTROL NOISE MINUS CRY AND UNIQUELY AC-

There
was only a small cluster more active with control noises
than cries. This cluster included the right somatosensory
cortex and right posterior insula. No brain regions were
uniquely active with control noises.

TIVE WITH CONTROL NOISE COMPARISONS.

Discussion
Hypothesized Findings
Consistent with our first hypothesis concerning emotional
ratings, mothers had higher ratings of sadness and urges to
help with cries than with control sounds and rest. Consistent with our second hypothesis regarding brain activity
with cry minus control noise, the anterior and posterior
cingulate cortices, medial thalamic nuclei, bilateral mesial
prefrontal cortex, and right orbitofrontal cortex were all
active. The anterior cingulate activation in this study was
pre- and supragenual in contrast to the subgenual activation of our pilot study. The mesial and right orbitofrontal
activity, however, did extend to the subgenual level
activity of our pilot study. Finally, we hypothesized that
these same regions would be uniquely active with cries.
Partially consistent with this hypothesis, all these regions
except the cingulate uniquely activated with the cries in
this experiment. Although thresholding effects may be
important in why the medial thalamus (i.e., part of the
thalamocingulate division) uniquely activated with cries
and the cingulate cortex did not, the medial thalamus can
be active independent of the cingulate. In fact, the medial
thalamus has strong connections with several regions that
are uniquely active with cry, including the paralimbic belt,
inferior dorsolateral and mesial prefrontal cortex, septal
region, and banks of the superior temporal sulcus (Mesulam 2000). That the cingulate cortex did not uniquely
activate with the cries means it is possible that its
activation with cry minus control noise may be due to
mere auditory perceptual, cognitive, or emotional enhancement; however, one should use caution in deciding
that regions more active with cries than control noises but
not uniquely active with the cries (such as the cingulate)
are unimportant in maternal behavior. These nonunique
regions could simply just be potentially more sensitive to
cries than other stimuli. Additionally, some neurocircuitry

BIOL PSYCHIATRY
2002;51:431 445

441

such as general circuitry like that involving selective


attention and approach and seeking behavior may not only
be important in maternal response to cries but also
important in response to nonsocial and novel stimuli such
as the white noise control sounds. Furthermore, wellestablished anterior cingulate functions such as selective
emotional and cognitive attention in responding to conflicting tasks are likely important in both cry and control
noise perception and response. Namely, one must inhibit
what one is doing to attend and respond to the cries. As the
control noises were more novel sounding and induced
more annoyance than the cries, they also could command
selective attention and cause anterior cingulate activity.

Nonhypothesized Findings Related to Previous


Studies of Mammalian Maternal Behavior
As described in the introductions final paragraph, there
are several nonhypothesized brain regions believed to be
important in rat maternal behavior. Many of these regions
activated with cry minus control noise including regions in
the vicinity of the hypothalamus/mammillary bodies, central gray/VTA, substantia nigra/retrorubral fields, caudate/
nucleus accumbens/globus pallidus/lateral septal region/
BNST, and putamen. All of these regions were
additionally uniquely active with cries. Furthermore, cryrelated activity within these midbrain, basal forebrain, and
basal ganglia structures as well as the cingulate/prefrontal
cortex is consistent with the notion that crying infants
might activate mesolimbic, mesocortical, and nigrostriatal
dopaminergic pathways involved in approach and seeking
behavior (Mello and Villares 1997; Mirenowicz and
Schultz 1996; Numan and Nagle 1983; Panksepp 1998).
Consistent with animal findings of amygdala involvement in maternal behavior (Kling and Steklis 1976), we
did find right amygdala activity with cries minus rest;
however, the right amygdala was also active with control
noise minus rest so that the cry minus control noise
comparison did not yield amygdala activity. This lack of
significant difference in amygdala activity between cries
and control noises may have been a function of control
sounds inducing more annoyance (a negative emotion)
than cries.
Lastly, consistent with the left-sided infant carrying/
right hemisphere maternal attachment theory discussed in
the introduction, brain activity with cry minus rest, cry
minus control noise, and uniquely active with cries was
predominately right-sided, whereas control noise minus
rest was more bilateral. This asymmetry was most pronounced in the right prefrontal and auditory/association
cortex. It should be noted that although this finding is
consistent with the right hemisphere maternal attachment
hypothesis, it is by no means proof. Many other plausible
explanations for greater right (than left) hemisphere acti-

442

BIOL PSYCHIATRY
2002;51:431 445

vation with the cries can be made. Many studies suggest


that the right hemisphere (particularly the right inferior
frontal gyrus) may be preferentially involved in receptive
emotional prosody, which is the ability to understand the
emotional information being conveyed by another person
(Bowers et al 1985; George et al 1996; Ross 1981;
Nakamura et al 1999). Some investigators also report that
negative affect (as may be induced by the cries) is linked
to the right prefrontal cortex (Davidson and Sutton 1995).
Furthermore, the right hemisphere activation observed in
our study may relate to a right hemisphere bias for low
frequency sounds that are frequently found in human
vocalizations (Ivry and Lebby 1998). Regarding this
possibility, the infant cries and control noises were
matched for intensity and temporal characteristics but
were not matched for frequency content. Although the
cries and control noises were broadband, there was more
low-frequency sound in the cries and more evenly distributed sound energy in the control noises. In a series of
fMRI studies of the human auditory cortex, Belin et al
(2000) found mainly right hemisphere activity with human
vocalizations as compared with amplitude and temporally
matched (but not frequency matched) nonvocal control
sounds. When matching the vocalizations and nonvocalizations for frequency in a later experiment, their activation pattern with human vocalizations was in the same
brain regions in the auditory cortex but became bilateral.

Functional Neuroimaging Studies of Love, Sadness,


and Cocaine Injection That Produced Patterns of
Activity Similar to This Study
Recently, Bartels and Zeki (2000) attempted to study the
functional neuroanatomy of love with fMRI by finding
brain regions more active with faces of a romantic partner
compared with faces of friends known for an equally long
period of time. This study is of interest because there may
be a common brain substrate for social attachment including maternal behavior and pair bonding. They found more
activity with the faces of a romantic partner than with the
faces of friends in the caudate, putamen, bilateral insula,
pregenual anterior cingulate (BA 24/32), posterior hippocampus (not viewed in our study), and cerebellum (not
viewed in our study). In the regions viewable in our study,
this pattern of activity with faces of a romantic partner can
best be characterized as a subset of the regions activated
with cry minus control noise. Of the regions previously
found to be important in maternal behavior that were
active in our study, notably absent from activity in this
romantic love study was the hypothalamus, midbrain,
thalamus, question of nucleus accumbens/lateral septal
region, and right ( left) hemisphere activity of our study.
The pattern of activation observed in our study is also
similar to some functional imaging studies of induced

J.P. Lorberbaum et al

sadness in healthy volunteers that commonly involved


induction tasks that related to social bonding (i.e., grieving
the loss of a loved one; George et al 1995; Lane et al
1997). This similarity is not surprising because our cries
induced higher feelings of sadness and urges to help
compared with control sounds. With sadness-inducing
autobiographical memories and external stimuli (i.e., sad
faces or films), Lane et al (1997) and George et al (1995)
both reported activity in the brain stem (with the Lane et
al [1997] study showing activity in the anterior midbrain/
hypothalamus/VTA vicinity and lateral midbrain/subthalamus), thalamus, caudate (with a question that part of this
activation may be nucleus accumbens or lateral septal
region in the Lane et al study), putamen, and pregenual
mesial prefrontal/cingulate cortex (BA 9/10/32) region.
These brain activity patterns of sadness were similar to the
brain activity pattern induced by listening to infant cries in
our study.
Curiously, in a cocaine infusion fMRI experiment,
Breiter et al (1997) found a pattern of activity similar to
our study particularly in regions where the dopaminergic
approach behavior pathways are located. Similar to our
study, Breiter et al (1997) found in cocaine-dependent
subjects that cocaine infusions relative to a preinfusion
baseline) increased brain activity in the substantia nigra/
VTA vicinity, medial thalamus, caudate, putamen, putamen/globus pallidus, nucleus accumbens/subcallosal gyrus, cingulate, and bilateral prefrontal cortex. Unlike our
experiment, they did not report activity in the vicinity of
the hypothalamus, central gray, septal region, or BNST or
a right hemisphere asymmetry to cortical brain activity.
That crying infants, viewing romantic partners, acute
sadness, and cocaine induce some similarities in brain
activity in regions where the dopaminergic approach
pathways are located could mean that all are tapping into
general circuitry important in processing appetitive (approach) stimuli.

Findings Relevant to Auditory Processing of


Species-Specific Vocalizations
Convincing evidence from primate neurobehavioral and
human functional imaging studies of the visual system
indicate that there exists 1) a specific region of the
fusiform gyrus in the occipitotemporal cortex that selectively responds to faces, 2) a ventral occipitotemporal
temporal lobeinferior prefrontal (BA 45/47) pathway for
object identity perception (what stream), and 3) a dorsal
occipitotemporalinferior parietal dorsal prefrontal (BA
8/46) pathway for object location perception (where
stream; Haxby et al 1994). Analogous to the visual system,
recent primate neurobehavioral and human studies of the
auditory system suggest that there exists 1) voice-sensitive

Thalamocingulate Circuitry and Maternal Behavior

regions located along the banks of the superior temporal


sulcus (STS), especially near Talairach points (63,13,1),
(56,30,6), and (62,14,0), which are consistently
more active with vocalizations (speech and nonspeech)
than with nonvocal control sounds; 2) a sound pattern
recognition stream (which appears to be more sensitive to
complex sounds such as voices) that proceeds anteriorly
along the STS toward the temporal pole and to lateral
inferior frontal/frontal polar regions (BA 10, 12/45/maybe
47); and 3) a dorsal sound location stream that proceeds
posteriorly along the STS to the inferior parietal lobe and
then to the dorsal prefrontal cortex (BA 46; Belin et al
2000; Rauschecker and Tian 2000; Romanski et al 1999).
In our study, the comparison of most relevance to these
findings is the cry vocalization versus the nonvocal white
noise control sound. Our experiment would be classified
as one of vocal sound detection rather than sound location
detection. Consistent with the above studies of voice
processing, we found more activation with cries than
control sounds along the banks of the STS. This includes
activity in Talairach points near the voice-sensitive central
STS points (63,13,1) and (62,14,0) reported by
Belin et al (2000); (see our Table 3). Consistent with a
ventral object processing stream of the cries, we also
found more activity with cries than control sounds along
the anterior STS (including the temporal polar region), in
the inferior frontal cortex (BA 45/47) and in the frontal
pole (BA 10) but not in the dorsal spatial processing
stream. Similar to Belin et al (2000), who used fMRI to
compare vocal with nonvocal sounds in the temporal lobe,
we found no auditory or audiovisual association cortex
region that had more activity with control sounds than
with a species-specific vocalization (cry).

Limitations
Several issues should be considered in interpreting our
findings. First, we used the same standard infant cry
recordings for all subjects. A mothers brain response to
hearing her own infant cry may be different (Wiesenfeld
and Klorman 1978). Second, we only studied mothers 1 to
2 months postpartum and did not have a control group of
fathers or nonmothers. Thus, we are unable to say that the
pattern of activity observed in this study was unique to
mothers. Third, one might argue that as the anterior
cingulate is known to be involved in attentional processing
(Bush et al 1998), a mothers increased cingulate response
with cries compared with control sounds may be simply a
function of attending more to meaningful baby cries than
to meaningless white noise control sounds. Although
selective attention is likely an important aspect of a
mothers response to infant cries, future studies with
attentional controls are needed. Fourth, it is possible that

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2002;51:431 445

443

the right hemisphere activation observed in our study may


relate to a right hemisphere bias for low frequency sounds
rather than to emotion itself (Belin et al 2000; Ivry and
Lebby 1998). This is because the infant cries and control
noises were matched for intensity and temporal characteristics but were not matched for frequency content.
Whereas the cries and control noises were broadband,
there was more low-frequency sound in the cries and more
evenly distributed sound energy in the control noises.
Better controls for frequency are important for future
studies. Fifth, several subjects had emotional responses to
the control noises, including a significantly higher annoyance response than to the cries in our study. In future
studies, factors such as emotional arousal, emotional
valence, sound familiarity, and humanness of the sound
should be considered as potentially important variables in
response to infant cries. Sixth, we did not view posterior
brain regions in our study. Furthermore, we did not use an
asymmetric spin-echo sequence, which limited viewing of
the orbitofrontal cortex and anterior temporal poles because of airtissue artifact. In future studies, we will
acquire whole brain data and convert to an asymmetric
spin-echo fMRI scanning sequence.

Conclusions
This study and our earlier pilot study are the first to use
modern techniques of functional imaging to study the
brain basis of human maternal behavior. Consistent with
our hypotheses, the cingulate, thalamus, mesial prefrontal
cortex, and right orbitofrontal cortex activate more when
mothers listen to infant cries than when they listen to white
noise control sounds. Partially consistent with our hypotheses, all these regions except the cingulate uniquely
activated with the cries in this experiment. Furthermore,
we also found that other regions believed to be potentially
important in rat maternal behavior studies activated with
cry minus control noise and were uniquely activated by
cries. Namely, we found activation in the vicinity of the
hypothalamus, central gray/VTA, substantia nigra/retrorubral fields, caudate/nucleus accumbens/globus pallidus/lateral septal region/BNST, and putamen. We also
found a right hemisphere asymmetry to cortical activity
consistent with the left-sided infant carrying hypothesis. In
sum, these results are generally consistent with those
found on the neural basis of maternal behavior in nonhuman mammals. Improved understanding of the regional
brain basis of parenting and social bonding more generally
would likely aid in research into normal emotions such as
love, separation anxiety, and grief. More knowledge
would also likely be important in understanding abnormal
behavior such as depression, anxiety disorders, schizophrenia, autism, and child maltreatment in which social
bonding problems may exist (Insel 1997).

444

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2002;51:431 445

We are indebted to Paul D. MacLean for planting the seed for the idea of
scanning mothers while they listen to infant cries. The authors thank Ken
Brown for his help with phone screening all subjects. The authors thank
both James C. Ballenger and George W. Arana for administrative
support. We would like to thank the Functional Neuroimaging Division
of the Medical University of South Carolina, Solvay Pharmaceuticals,
and National Institute of Health Grant No. R01 NS 40259 for supporting
the current project.

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