1Cognitive Neuroscience and Schizophrenia Program, Nathan Kline Institute for Psychiatric Research, Orangeburg 10962; 2Department of Neuroscience, 3Department of Neurology, and 4Department of Neurosurgery, Albert Einstein College of Medicine, Bronx 10461; and 5Department of Psychiatry, New York University Medical Center, New York, New York 10003
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ABSTRACT |
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Schroeder, Charles E., Robert W. Lindsley, Colleen Specht, Alvin Marcovici, John F. Smiley, and Daniel C. Javitt. Somatosensory Input to Auditory Association Cortex in the Macaque Monkey. J. Neurophysiol. 85: 1322-1327, 2001. We investigated the convergence of somatosensory and auditory inputs in within subregions of macaque auditory cortex. Laminar current source density and multiunit activity profiles were sampled with linear array multielectrodes during penetrations of the posterior superior temporal plane in three macaque monkeys. At each recording site, auditory responses to binaural clicks, pure tones, and band-passed noise, all presented by earphones, were compared with somatosensory responses evoked by contralateral median nerve stimulation. Subjects were awake but were not required to discriminate the stimuli. Borders between A1 and surrounding belt regions were identified by mapping best frequency and stimulus preferences and by subsequent histological analysis. Regions immediately caudomedial to A1 had robust somatosensory responses co-represented with auditory responses. In these regions, both somatosensory and auditory response profiles had "feedforward" patterns; initial excitation beginning in Lamina 4 and spreading to extragranular laminae. Auditory and somatosensory responses displayed a high degree of temporal overlap. Anatomical reconstruction indicated that the somatosensory input region includes, but may not be restricted to, the caudomedial auditory association cortex. As was earlier reported for this region, auditory frequency tuning curves were broad and band-passed noise responses were larger than pure tone responses. No somatosensory responses were observed in A1. These findings suggest a potential neural substrate for multisensory integration at an early stage of auditory cortical processing.
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INTRODUCTION |
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The brain's ability to
combine inputs from different sensory modalities yields an enriched
description of objects as well as converging evidence concerning their
position, movement, and identity. For such "multisensory
integration" to occur, requires that at some point in sensory
processing, excitatory signals arising from different sense modalities
converge onto either single neurons or interconnected ensembles of
neurons. In the first case, single neurons would be directly excitable
through each modality. In the second case, single neurons would be
excitable through one modality and might also be subject to more subtle
modulatory influences (excitatory and/or inhibitory) from the other.
Although neither type of convergence guarantees occurrence of
multisensory interactions (Stein and Meredith 1993),
they collectively provide the necessary anatomical substrates for such
interactions. Definition of the brain areas in which convergence occurs
is therefore fundamental to our understanding of the brain mechanisms
of multisensory processing and integration.
Prior studies in primates have demonstrated multisensory convergence in
parietal (e.g., Duhamel et al. 1998; Hyvarinen
and Shelepin 1979
), temporal (e.g., Benevento et al.
1977
; Bruce et al. 1981
; Leinonen et al.
1980
), and frontal regions of neocortex (e.g., Graziano
et al. 1994
; Rizzolatti et al. 1981
). It is
noteworthy that these studies typically find both "multisensory"
neurons with clear excitatory inputs from two or more modalities (i.e., convergence at the neuronal level) and, in the same cortical area, intermingled populations of apparently "unimodal" neurons with different input sources (i.e., convergence at the areal/ensemble level).
The present study expands on a preliminary finding of a somatosensory
input to auditory association cortex. Our methods entail analysis of
current source density (CSD) and multiunit action potential profiles
sampled with linear array multielectrodes in awake monkeys. CSD
analysis provides an estimate of transmembrane current flow, which is
the first-order response to synaptic input. Analysis of concomitant
multiunit activity reveals the degree to which synaptic activity
generates a net change in local action potentials. Collection of these
measures with a linear array electrode enables us to gauge the laminar
activation sequence, which helps to differentiate feedforward from
feedback and lateral input patterns (Schroeder et al. 1995,
1998
). While these methods do not address convergence at the
single neuron level, they provide for an efficient, well-controlled
evaluation of multisensory convergence at the neuronal ensemble level.
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METHODS |
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One rhesus and two cynomologus macaques (Maccaca
mulatta and M. fascicularis), weighing 5-8 kg, were
prepared for chronic awake recording used aseptic techniques, under
general anesthesia (pentobarbital sodium, 25-35 mg/kg iv)
(Schroeder et al. 1998). During recording, animals were
monitored continuously using electroencephalography (EEG) and video
displays and were maintained in an alert state but were not required to
attend or discriminate stimuli in any sensory modality. Laminar CSD and
multiunit activity (MUA) profiles were collected bilaterally from sites
in A1 and the adjacent regions posterior to A1, concentrating on
caudomedial (CM) auditory cortex. CSD profiles were calculated from
field potential profiles using a three-point formula for estimation of
the second spatial derivative of voltage (Freeman and Nicholson
1975
; Nicholson and Freeman 1975
). MUA was
obtained from the signal at each contact by high-pass filtering the
amplifier output at 500 Hz to isolate action potential-frequency activity, full-wave rectifying the high-frequency activity, and averaging the single sweep responses together. With the rectification step, each averaged MUA tracing (see e.g., Fig.
1) is in effect an action potential
histogram; upward deflection represents activity increase and downward
deflection represents activity decrease relative to the prestimulus
baseline. See Schroeder et al. (1998)
for further
details and illustration of these methods.
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Figure 1 illustrates the positioning of the electrode array for laminar profile analyses. For quantification, CSD profiles were full-wave rectified, then averaged into a single waveform (AVREC; see Fig. 1), and grand mean responses were computed across subjects.
Auditory stimuli were delivered at 65 dB (SPL) binaurally through
Sennheisser HD565 headphones coupled with 50-ml tubes placed against
the external auditory canal (Javitt et al. 1996). A
combination of 100-µs clicks and 100-ms pure tones and band-passed
noise (5 ms on/off ramps) was used to characterize best frequency and
to optimize stimulation at each recording site. For routine assessment of the best frequency at each site, we analyzed responses to pure tones
presented at 2/s (Steinschneider et al. 1998
).
Specifically we measured the peak of the MUA onset, in a window of
0-50 ms poststimulus, at the Lamina 3-4 border. At each site, a first approximation of the tuning curve was derived by taking this
measurement from responses to 0.5, 1, 2, 4, 8, 16, 20, and 30 kHz. In
some cases, the tuning estimate was further refined as indicated by the
first approximation, but the first approximation was the only measure
available for all recording sites.
Averaged responses to optimized stimuli were obtained at each recording
site. Co-located somatosensory responses were quantified using
electrical stimulation of peripheral nerves from the hand; 100-µs
square-wave (constant current) electrical pulses were delivered with
gold cup EEG electrodes to the skin over the median nerve in the
forearm contralateral to the recording site (Peterson et al.
1995; Schroeder et al. 1995
, 1997
) and constant
80-dB white noise masked any co-incident auditory stimulation. It was
established earlier that repetitive electrical stimulation of the
median nerve at the wrist produces an averaged response in
somatosensory cortex, extremely similar to that produced by repetitive
cutaneous stimulation of the appropriate (radial) half of the glabrous
hand surface. Specifically, Schroeder et al. (1995)
showed that in "median nerve territory in primate Area 3b, the timing
and distribution of action potentials and CSD components evoked by
electrical stimulation of median nerve and by stimulation of the volar
surface of digit 1, were equivalent" (see Schroeder et al.
1995
, Fig. 1 vs. 3A). In the same recording site,
neither electrical stimulation of the ulnar nerve nor cutaneous
stimulation of the volar surface of digit 5 produced a measurable
response (Schroeder et al. 1995
, Figs. 2B and
3C). Thus median nerve electrical stimulation clearly produces a specific "somatosensory" response. In the present study, the definition of the median nerve-evoked response as a somatosensory response is supported by the specificity of its cortical distribution (see following text).
Recording sites were confirmed by histological analyses. Serial
sections were made and every third one was stained for Nissl substance,
acetylcholine esterase (AchE) or parvalbumin (PV) to help determine the
borders between A1 and surrounding regions (Hackett et al.
1998; Kosaki et al. 1997
; Morel et al.
1993
).
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RESULTS |
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Areal convergence of somatosensory and auditory inputs, as
illustrated in Fig. 1, was found in 10/18 sites we examined that were
in auditory cortex, immediately posterior to A1. As detailed in the
following text, somato-auditory convergence sites were concentrated in
the caudomedial (CM) belt region of auditory association cortex. The
laminar profiles of co-represented auditory and somatosensory responses
describe a characteristic activation sequence triggered by ascending
synaptic inputs in sensory cortex (Schroeder et al. 1995,
1998
; Steinschneider et al. 1998
): initial
depolarization of input terminals in and near Lamina 4, along with
discharge of stellate cells, producing a current sink over source
configuration (lower boxes) and associated action potentials, followed
by excitation of supra- and infragranular pyramidal cells. To allow
better visualization of the temporal pattern of synaptic activation in
Lamina 4 and lower Lamina 3, data from an additional somatosensory
input site in auditory cortex are presented on an expanded scale in
Fig. 2. The excitatory CSD configuration
in supragranular pyramidal cells is typically source/sink (upper boxes,
Fig. 1), with associated action potentials displaced below this to the
base of Lamina 3. With the stimuli used here, only the initial phase of
excitation in the pyramidal cell ensemble is reflected in action
potentials.
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Under the present conditions, somatosensory and auditory responses in CM begin at nearly the same time and have similar amplitude at the first response peak; however, the former tend to have larger amplitude during the later time course of the response. This is shown by representative patterns of auditory and somatosensory response from single penetration sites in each of the three monkeys (Fig. 3A) and the grand mean data for the same conditions, across subjects, in CM (Fig. 3B).
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A1 penetrations, as distinguished by anatomical location (see
penetration 1, Fig. 4A),
demonstrated no somatosensory responsiveness (Fig. 3C). This
fact supports the sensory specificity of the median nerve-evoked
response (Schroeder et al. 1995). Sites displaying somato-auditory co-representation were located in the caudal
belt/parabelt regions. Reconstruction of three penetrations through
this region is illustrated in Fig. 4B. Two of these were in
medial sites (3 and 4) and showed clear somatosensory responsiveness,
while the penetration through a more lateral site (2) showed none. All
sites discussed in this report had robust auditory responses. The
overall distribution of auditory alone and somato-auditory convergence sites is represented in Fig. 4C. As illustrated there,
somato-auditory convergence sites appeared concentrated in the CM but
may extend posterior to CM into the adjacent parabelt.
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As reported earlier (Merzenich and Brugge 1973;
Rauschecker et al. 1995
, 1997
; Recanzone et al.
2000a
), frequency tuning in posterior sites (Fig.
5, B and C) was
broad relative to that in A1 (Fig. 5A). This is apparent
even with the approximation methods used in this study. With the same
methods, the sharpness of best frequency tuning in sites showing
somatosensory input in the regions posterior to A1 (Fig. 5B)
cannot be distinguished from that in sites unresponsive to median nerve
stimulation (Fig. 5C). We would not rule out the possibility
that more precise testing in a larger sample would show such a
distinction.
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DISCUSSION |
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The present study demonstrates areal convergence of somatosensory
and auditory inputs within posterior auditory association cortex in the
macaque monkey. The convergence appeared concentrated in Area CM but
may not be confined to this area. Because CM represents an early stage
of cortical auditory processing, only one step removed from A1
(Kaas et al. 1999; Rauschecker et al.
1997
; Recanzone et al. 2000b
; Romanski et
al. 1999
), the somatosensory input is unexpected. The only
functional indications of somato-auditory convergence in this region
are indirect and come from human experiments. Magnetoencephalographic
recordings (Levanen et al. 1998
) have localized
vibration-induced activation within auditory cortex in congenitally
deaf humans. Although it should be emphasized that this result has not
been shown in subjects with normal hearing, event-related potential
(ERP) studies in normal humans have observed short-latency
somato-auditory integration effects having a time course and voltage
topography consistent with an ERP generator source in the superior
temporal plane (Foxe et al. 2000
).
Both the auditory and somatosensory activation profiles in CM have a
characteristic "feedforward" pattern, predicted by the anatomy of
feedforward projections (Rockland and Pandya 1979); excitation begins in Lamina 4 and spreads to the extragranular layers
(Fig. 2). Although spatially overlapping neuronal populations in CM are
clearly activated by each modality (areal convergence), the proportion
of local neurons that exhibit excitatory somato-auditory convergence
relative to those with unisensory excitatory input remains to be determined.
Even assuming that there is excitatory convergence in a high proportion of single neurons, the strength and nature of any resulting multisensory interactions is an open question, which we are presently unable to resolve. We regard the actual integration of somatosensory and auditory input within CM neurons as a likely possibility, although alternatives are equally interesting. Independent use of single neurons (or intermingled populations of neurons) by separate sensory modalities, for example, would represent a novel and intriguing use of cortical architecture.
An earlier study observed somato-auditory convergence within single
units in area Tpt (Leinonen et al. 1980), but Tpt is
within the "parabelt" region of auditory cortex (Hackett et
al. 1998
), whereas our recordings were mainly in CM, which
corresponds to a part of the "belt" region of auditory cortex
(Hackett et al. 1998
). Several studies have suggested
that body maps exist in the region caudolateral to the insula and
SII/PV cortices (Burton and Robinson 1981
;
Krubitzer et al. 1995
; Leinonen 1980
;
Robinson and Burton 1980
). However, because none of
these investigated somato-auditory convergence, the degree of
correspondence, if any, between the somatosensory inputs we describe
and those defined earlier is not yet clear.
In the present study, somatosensory stimulation was confined to the
afferents from the hand, and thus we cannot comment on the nature of
the body map in CM. Krubitzer et al. (1995) reported one
or more partial body maps that abut the SII/PV body maps in the fundus
of the lateral sulcus and extend out onto the superior temporal plane;
that is, into a region that very likely includes CM. This finding
clearly predicts the somato-auditory convergence we report here but
does not tell us whether CM contains a full body map or a
representation that is biased toward a particular surface(s), similar
to the "hand-" and "face-biases" found for somatic input to
visual areas MIP and VIP (Duhamel et al. 1998
). This question is a specific target of our ongoing studies.
The functional significance of somato-auditory convergence in CM may be
related to spatial localization in keeping with the hypothesis that the
caudal auditory cortices in general are specialized for this function
(Kaas 1999; Rauschecker et al. 1995
;
Romanski 2000
). There does appear to be spatial
correspondence between the auditory and somatosensory receptive fields
of Tpt neurons (Leinonen et al. 1980
), but this has not
been investigated in CM. While there are only a few studies of spatial
receptive fields in auditory cortical neurons (Ahissar et al.
1992
; Benson et al. 1981
; Recanzone et
al. 2000
), one of these does suggest a special role for CM in
sound localization (Recanzone et al. 2000
). A related possibility is that caudal auditory regions are part of a network that
combines vestibular with other sensory inputs to compute the position
of the head in space and/or in relation to the other parts of the body
(Gulden and Grusser 1998
). Somato-auditory convergence would be extremely useful in such computations.
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ACKNOWLEDGMENTS |
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We thank Dr. P. Thier for helpful discussion on vestibular system projections and J. J. Foxe, T. McGinnis, E. Dias, and R. Feldman for technical and conceptual assistance.
This work was supported in part by National Institute of Mental Health Grants MH-61989 and MH-55620.
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FOOTNOTES |
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Address for reprint requests: C. E. Schroeder, Cognitive Neuroscience and Schizophrenia Program, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd., Bldg. 37, Orangeburg, NY 10962 (E-mail: schrod{at}nki.rfmh.org).
Received 12 June 2000; accepted in final form 10 October 2000.
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REFERENCES |
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