Polysensory responses and sensory interaction in pulvinar and related postero-lateral thalamic nuclei in cat

265

Electroencephalography and Clinical Neurophysiology, 1973, 34 : 265-280 © Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands

POLYSENSORY PULVINAR

AND

RESPONSES RELATED

AND

SENSORY

INTERACTION

POSTERO-LATERAL

THALAMIC

IN NUCLEI

IN CAT 1 CHUONG C. HUANG 2 AND DONALD B. LINDSLEY

Departments of Psychology and Physiology, and Brain Research Institute, University of California, Los Angeles, Calif. 90024 (U.S.A.) (Accepted for publication: June 30, 1972)

In the course of the progressive encephalization of the brain the pulvinar and the other posterior associational nuclei have shown markedly increased growth. Partly because of its size in monkey and man and partly because of the importance of the cortical regions to which it projects, the pulvinar has been hypothesized to have a very important integrative role (Walker 1938, 1955; Hassler 1955). Its magnitude in man parallels the extent of encephalization in occipital, parietal and temporal lobes and, more specifically, its central focus of projection is to the region of the supramarginal and angular gyri where these three lobes meet and where lesions are known to give rise to deficits in man's highest cognitive and elaborative functions, namely, the symbolic formulation of speech, language and thought. The functional role of the pulvinar and related postero-lateral thalamic association nuclei has not been investigated extensively and is not well understood. However, responses have been recorded in some of these nuclei to somatosensory stimuli (Mountcastle and Henneman 1949, 1952; Albe-Fessard and Bowsher 1965), to photic stimuli (Battersby and Osterreich 1963; Hotta and Terashima 1965; Godfraind et al. 1969; Koenig and i Supported by grants from the Office of Naval Research (N00014-69-A-0200-4024), National Aeronautics and Space Administration (NASA NGL 05-007-049) and U.S. Public Health Service (NS-8552). Aided by National Institutes of Mental Health Training Grant 5 T1 MH-6415. 2 Present address: Missouri Institute of Psychiatry, 5400 Arsenal Street, St. Louis, Mo. 63139 (U.S.A.)

Frazier 1969; Suzuki and Kato 1969), and to auditory stimuli (Buser et al. 1959; Buser and Bruner 1960; Hotta and Kameda 1963). The possible integrative role of these nuclei has been further suggested by their polysensory responses to visual, auditory and somatosensory stimuli (Buser et al. 1959; Bruner 1965; Calma 1965; Kreindler et al. 1968). Chow (1954) has studied the behavioral effects of lesions. In order to clarify the sensory projection of visual, auditory and somatosensory modalities to the posterior part of the lateral thalamic nuclear group in cats, it was considered desirable to do a systematic mapping of these areas. Accordingly electrophysiological responses to visual, auditory and somatosensory stimuli were recorded under two conditions: chloralose, and in the unanesthetized brain (Flaxedil). Responses were also recorded under barbiturate anesthesia but were generally less satisfactory and will not be discussed. Data on onset latencies, recovery cycles of evoked responses for each of the sensory modes and intermodality interactions are presented. Preliminary micro-electrode observations are reported. MATERIAL AND METHODS

Following extensive pilot investigations, 36 cats were used in the final studies. Surgery, including tracheal cannulation, was done under deep ether anesthesia. After placement in a Johnson stereotaxic instrument the marginal and suprasylvian gyri were exposed bilaterally. A pool of warm mineral oil was maintained

266 over the exposed brain. Screw electrodes were embedded in the skull over auditory and somatosensory cortex; a silver ball-tipped electrode was employed for recording from exposed visual cortex. Upon completion of surgery, all wound margins and pressure points were infiltrated carefully with 1 ~ procaine hydrochloride (repeated every 2 h), ether anesthesia was discontinued, and the animal was immobilized with a suitable infusion of gallamine triethiodide (Flaxedil) via a catheter in a foreleg vein. Supplementary infusions were given at hourly intervals. Artificial respiration was used throughout the experiment and body temperature was maintained by a heating pad. For the chloralose condition, alpha chloralose (70 mg/kg) dissolved in saline was infused and the remaining procedures were the same as for the Flaxedil condition, including light flaxedilization. The animal was placed in a light-tight chamber and al.lowed to dark-adapt. The pupil of the eye to be stimulated was fully dilated with 2~o homatropine sulfate and mydriasis was maintained throughout. The lids of the eye stimulated were retracted and the other eye was covered with an opaque shield. A 0.5 mm in diameter stainless-steel concentric electrode probe, insulated except for a 1 mm protruding inner shaft and the bared edge of the outer shaft was used to record in posterior thalamic regions the responses to flash, click, and mild electric shock to the contralateral forepaw. Stimulating and recording procedures. A Grass PS-I photostimulator, provided light flashes of 20 psec duration. The flash lamp was mounted on the outside of an optical box, adjacent to the light-tight box containing the animal, 1 m distant from the eye of the cat. At this distance with the walls of two boxes intervening no audible click from the photostimulator could be heard inside the light-tight box. The optical system permitted the focussing of an 8 mm diameter circular spot on the cornea of the eye stimulated. The intensity of the light flash was approximately 4 log units above the darkadapted electrophysiological threshold response at visual cortex. Auditory stimulation consisted of sharp clicks

C. C. H U A N G AND D. B. LINDSLEY

produced by a 3 in. loudspeaker mounted near the cat's ear. Clicks occurred once every 7 sec. Somatosensory stimulation was delivered by a Grass S4-B physiological stimulator and a Grass SIU-4 stimulus isolation unit through needle electrodes inserted in the forepaw; pulse duration was 0.25 msec at 4 6 V and repetition rate was 1 every 7 sec. Electrical responses were recorded on a Grass Model IIID electroencephalograph with an effective bandwidth from 1 to 100 c/sec and on a Tektronix 502 oscilloscope coupled to Grass P5 pre-amplifiers with a bandwidth of 1.5 c/se~10 kc/sec. Photographs of single and superimposed responses were obtained with a Grass C-4 Kymograph Camera. A stimulus pip appears on each trace shortly after the start of the oscilloscope sweep. Procedures for mapping evoked responses in pulvinar and adjacent regions, and procedures for recovery cycle and intermodality interaction tests are described in detail in their respective subsections under Results. Micro-electrode recordings in the pulvinar were made under the Flaxedil condition only using visual stimuli. Tungsten micro-electrodes were used. At the conclusion of each experiment the brain was perfused with 1 0 ~ formalin and removed after identification of surface recording sites. After a period of fixation the location of thalamic recording sites was determined carefully from photographs of frozen sections (Guzman-Flores et al. 1958) and from thionin stained sections. RESULTS

I. Mapping of evoked responses in the regions of the pulvinar A systematic mapping of evoked responses to visual, auditory and somatosensory stimuli in a region encompassing the pulvinar and adjacent nuclei was carried out under chloralose anesthesia and in the unanesthetized brain (Flaxedil). The region of the mapping, as shown in Fig. 1, is demarcated by a square in each of the three frontal planes, A4, A6 and A8. It includes horizontal planes H + 8 to H + 2 and lateral planes L4 to L10. A complete mapping

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Fig. 1. Regions of the postero-lateral thalamus, including pulvinar and other association nuclei of the lateral group, systematically mapped and studied electrophysiologically. Square defines regions on three frontal plane sections, A4, A6 and A8. Histology from Atlas of Snider and Niemer (1961); diagrams from Jasper and Ajmone Marsan (1954). Abbreviations: Aq, Aqueduct ; CC, N. centralis centralis; C.C., corpus callosum; CM, N. centralis medialis; Fx, fornix; GL or LG, lateral geniculate body; GM or MG, medial geniculate body; Hb, N. habenulae lateralis; Hp, hippoeampus; LD, N. lateralis dorsalis; Lim, N. limitans; LP, N. lateralis posterior; MD, N. medialis dorsalis; P, N. posterior; Prt, pretectal area; Pul, pulvinar; R, N. reticularis; r.f., reticular formation; SG, N. suprageniculatus; TO, optic tract; VPL, N. ventralis posterior lateralis; VPM, N. ventralis posterior medialis.

of this region in the right or left thalamus in a particular cat, with electrode tracks spaced 2 mm apart, would require 12 electrode penetrations. In order to avoid a "pincushion effect" only two electrode penetrations, at least 4 mm apart, were made in each thalamus. Each of the evoked potential maps shown is a composite based upon recordings from 6 cats whose records were technically good and representative in configuration and location. All of the evoked potentials in a given vertical column were made with the same electrodes in the same cat. Each vertical column of responses was selected from among as many as 6 cats with penetrations at that location. Along a given electrode probe track the sequences of stimulation (visual, auditory and somatosensory) were changed with each lowering of the recording electrodes. After each electrode shift the background electrical activity from each recording site, monitored continuously by EEG, was allowed to stabilize before

sensory stimulation was begun. A. Responses under chloralose In appropriate dosages, chloralose anesthesia depressed background electrical activity but enhanced both primary and secondary responses. Thus it proved efficacious for the study of evoked responses in posterior association nuclei. Fig. 2 shows the distribution of evoked responses to visual, auditory and somatosensory stimuli under chloralose anesthesia. All regions of the pulvinar, N. lateralis posterior, N. posterior, N. suprageniculatus and the posterior part of N. lateralis dorsalis gave responses to visual, auditory and somatosensory stimuli but the magnitude of these responses differed greatly in the different regions. The characteristic response was usually a long-latency, shortduration, positive wave followed by a larger and longer-duration negative wave. The distribution of the responses for the three individual sense modes, though widespread throughout these structures, tended to

268

C. C. HUANG AND D. B. LINDSLEY

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Fig. 2. Composite distribution of visual, auditory and somatic evoked responses in pulvinar and associated posterior thalamic nuclei in frontal planes A4, A6 and A8 under chloralose anesthesia. Height in millimeters at left ; laterality in millimeters at bottom. Concentric electrodes: negativity at tip gives upward deflection. Calibrations: 50/~V, 40 msec. (See legend Fig. ! for abbreviations.)

show amplitude differences and regional clustering. For example, good visual responses were more highly concentrated in the postero-lateral region (A4 and A6, L6 to L10) which corresponded roughly with the extent of the pulvinar, N. posterior, N. suprageniculatus and the posterior part of N. lateralis posterior. In contrast, visual responses were of small amplitude in the anterior part of N. lateralis posterior (A8, L4 and L6). It is of interest to note that in the A4, L4 column

only one locus at H4 showed a good response to visual stimulation and that was in the pretectal region adjacent to N. suprageniculatus and the pulvinar (this also was true under Flaxedil). Visual responses from the region of the optic tract and lateral geniculate body (A4 to A8, L10) were more complicated in pattern and of shorter latency. In contrast to visual responses which were more prominent postero-laterally, the largest

EVOKED POLYSENSORY RESPONSES IN PULVINAR

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Fig. 3. Composite distribution of visual, auditory and somatic evoked responses in pulvinar and associated posterior thalamic nuclei in frontal planes A4, A6 and A8 in unanesthetized brain (Flaxedil). (For other details and abbreviations see legends for Figs. 1 and 2.)

somatosensory responses occurred predominantly in antero-ventro-medial regions (A6 to A8, L4 to L8). Thus just as a clustering of good visual responses was found in regions bordering the lateral geniculate nucleus, the most prominent somatosensory responses tended to cluster around N. ventralis posterior lateralis (VPL) and N. ventralis posterior medialis (VPM). Auditory responses were more diffusely distributed than either visual or somatosensory

responses, however, the more prominent auditory responses tended to be located in posteroventro-lateral regions, near the medial geniculate nucleus. Although visual responses were expected in visual structures such as optic tract and lateral geniculate body, it is of interest to note that responses to auditory and somatosensory stimuli also appeared there. This is not due, however, to chloralose anesthesia since similar but smaller

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H U A N G AND D. B. LINDSLEY

TABLE 1 Means and standard deviations of onset latencies for visual, auditory and somatosensory responses in specific relay nuclei, and in postero-lateral thalamic nuclei. Chloralose anesthesia. Stimuli

Visual Auditory Somatosensory

Mean S.D. Mean S.D. Mean S.D.

Specific thalamic relay nuclei*

Pulvinar

N. lat. post.

N. suprageniculatus

N. posterior

N. lat. dorsalis

23.38 LG 0.99 9.86 M G m 0.71 7.03 VB 0.30

27.59 1.09 10.56 0.52 18.04 1.79

29.01 1.33 11.28 0.40 17.57 2.25

26.90 3.87 9.75 0.78 13.38 1.77

23.25 0.92 12.30 0.42 21.45 0.50

29.57 3.65 9.70 2.16 21.20 6.86

* LG, lateral geniculate; M G m , medial geniculate, magnocellular; VB, ventrobasal nuclei, VPM or VPL.

responses occurred there also in the unanesthetized brain (Flaxedil). B. Responses in the unanesthetized brain Fig. 3 shows the distribution of evoked responses to visual, auditory and somatosensory stimuli in postero-lateral thalamic association nuclei in unanesthetized brain preparations under Flaxedil. There was more spontaneous background activity than under chloralose, but the evoked responses were of smaller amplitude and of shorter latency. The characteristic response consisted of a positive wave, usually followed by a longer duration negative wave. As was found under chloralose anesthesia, most regions of the pulvinar, N. lateralis posterior, N. posterior and N. suprageniculatus yielded responses to visual and auditory stimulation in the preparations without general anesthesia. In general, however, the responses were not as diffusely distributed. In unanesthetized brain preparations there was a better regional differentiation of responsiveness for the individual sense modes and less widespread overlapping than under chloralose anesthesia. Somatosensory stimulation elicited almost no response in those regions which were responsive to visual and auditory stimuli, and only the ventral region of the posterior associational nuclei (A4 to A8, L4 to L8) showed somatosensory responses of small amplitude. It was clear that visual stimulation showed more prominent responses in the postero-lateral regions, especially in the pulvinar and N. lateralis

posterior (A4 and A6, L6 and L8). Auditory responses were of largest amplitude in posteroventral regions (A4 and A6, L6 to L10); auditory responsivity was generally poor in the more anterior regions (A8, L4 to L10). II. Response latencies in thalamic nuclei Onset latencies of evoked responses were measured for each recording site. The total number of responses from which latency measures were obtained at each site was approximately 80-90 and involved from 3 to 6 cats. Table I shows the mean onset latencies for visual, auditory and somatosensory responses in specific thalamic relay nuclei and in nuclei of the postero-lateral associational group. In most of the latter the mean latencies were longer than those of responses in specific relay nuclei and also those recorded in primary sensory cortical areas (not included in Table I). Cortical latencies were recorded from only one site and did not include dispersed non-specific or association areas from which longer latencies are typically obtained. In the case of visual stimulation, except for N. posterior, which had a latency similar to that of the lateral geniculate nucleus, the response latencies of the postero-lateral associational nuclei ranged from about 4 to 6 msec longer than those of the lateral geniculate nucleus. With respect to auditory stimulation, the latencies in the postero-lateral association nuclei were only slightly longer than those of the medial geniculate nucleus, the differences

EVOKED POLYSENSORY RESPONSES IN PULV1NAR TABLE I1 Means and standard deviations of onset latencies for visual, auditory and somatosensory stimuli at recording sites in different frontal planes of the pulvinar. Chloralose anesthesia. Pulvinar

Stimuli

A 4.0*

Visual Auditory Somatosensory

Mean S.D. Mean S.D. Mean S.D.

27.50 0.70 10.25 0.21 14.85 0.25

A 6.0*

A 8.0*

Lat.

Med.

25.03 1.99 12.07 1.97 26.43 3.13

29.63 2.90 10.03 1.35 18.23 0.89

28.20 2.70 9.90 1.41 12.65 0.65

* Horsley-Clarke coordinates: A 4.0, L 6.0, H + 6 . 0 ; A 6.0, L 8.5 and L 5.5, H + 7 ; A 8.0, L 7.5, H+6.0.

ranged from about 1 to 3 msec, except for N. suprageniculatus and N. lateralis dorsalis which had latencies similar to those of the medial geniculate. In contrast to auditory and visual responses, the somatosensory response latencies in postero-lateral association nuclei were much longer than in the specific relay nuclei, VPM and VPL (referred to in the table as ventrobasal nuclei, VB). The latencies of somatosensory responses in the associational nuclei ranged from 2 to 3 times longer than in VB nuclei. Table II presents a regional distribution of latencies in the pulvinar for visual, auditory and somatosensory stimuli. In general, visual latencies were the longest and auditory latencies were the shortest, with somatosensory latencies intermediate. Regional differences (A4 to A8) in latency within the pulvinar were statistically significant for only the somatosensory modality. Somatosensory latencies within the pulvinar were shortest in its most anterior region (A8), adjacent to VPM and VPL. Regional differences for visual and auditory stimuli, while not significant statistically, tended to show shorter latencies in those regions of the pulvinar nearer their respective specific relay nuclei, i.e., in the postero-lateral region of the pulvinar for vision and in the postero-ventro-lateral region for audition. A detailed comparison of the mean onset

271 latencies under chloralose anesthesia and under the Flaxedil condition (unanesthetized brain) was made for visual stimuli. In the unanesthetized brain the latencies were consistently 4-8 msec less in the optic tract, lateral geniculate body, optic radiations, pulvinar and other postero-lateral association nuclei. Reductions in latency in non-anesthetized animals versus chloralose preparations were observed also for auditory and somatosensory stimuli although these were not studied in detail. IlL Recovery cycle tests In order to determine the physiological characteristics of responses from particular areas, successive recovery cycle tests were carried out under chloralose anesthesia. The method employed was as follows: trains of 10 stimuli were presented at rates of 0.5, 1, 2, 3/sec etc. to 10/sec followed by repeated series at 1/sec and 0.5/sec. The peak-to-peak amplitude for initial positive and negative waves was measured. The amplitude of the 5th or 6th response in a series at 0.5/sec (1 stimulus per 2 sec) was taken as a base measure (100~) and the amplitude of the 5th or 6th response in all other frequency series was plotted as a percentage of it. Thus"fatiguability" or successive recovery cycles were measured in terms of relative amplitude percent as a function of the inter-stimulus interval (ISI). Fig. 4 presents six graphs of recovery cycle functions for the three sense modes: visual, auditory and somatosensory. The upper three are for specific (primary) sensory pathways and structures and the lower three are for the nonspecific, polysensory, postero-lateral thalamic association nuclei. In genera[ the primary or specific sensory pathways and structures show recovery functions of similar nature, i.e., from the control or base level measure at an ISI of 2.0 sec there is slight enhancement of the test response at 1.0 or 0.5 sec, with a drop in amplitude occurring from an ISI of 0.5-0.1 sec. In contrast the non-specific, postero-lateral thalamic nuclei follow a linear trend downward from an ISI of 2.0 sec, with the exception of N. suprageniculatus (lower right graph) whose function resembles more that of the primary specific sensory structures. In summary of recovery cycle functions, it

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may be noted that there were three levels of speed of recovery exhibited: fast, intermediate and slow. Primary or specific sensory pathways (optic tract and radiations) and structures (relay nuclei M G (medial geniculate), LG (lateral geniculate) and VPL) showed relatively fast recovery, in the main showing marked response decrement only at the upper frequency limits of the range tested (ISis of 0.1 and 0.2 sec). Primary sensory cortex for all three modalities, and also N. suprageniculatus, showed an intermediate speed of recovery with considerable decrement of response at ISis of 0.5 sec and marked decrement at ISis below that value. The nonspecific or associational nuclei of the posterolateral thalamus, specifically the pulvinar and N. lateralis posterior, showed steady decrements of the response from an ISI of 2.0 sec downward and nearly zero response at an ISI of 0.1 sec.

The pattern of recovery for these thalamic associational structures was similar to that described by Thompson et al. (1963) for cortical association areas. The regional differences in recovery cycle functions for the posterior association nuclei corresponded generally to the predominant focus of responsiveness for each modality revealed in the mapping of their evoked potentials, i.e., those regions showing greater amplitude and shorter latency of response in the case of each sense mode had the best recovery functions. Of special interest is the fact that N. suprageniculatus, which showed shorter latencies for all modalities (see Table I) than did the pulvinar or N. lateralis posterior, also exhibited faster recovery cycles for all three modalities (see lower right graph, Fig. 4).

273

EVOKED POLYSENSORY RESPONSES IN PULVINAR

IV. Intermodality interaction Intermodality interaction has been studied in terms of the effect of a response to a stimulus in one sensory mode upon the response to a stimulus in a different mode which follows at varying ISis ranging from + 900 to - 1 0 msec. Intermodality interactions were recorded in specific sensory relay nuclei of the thalamus and in non-specific association nuclei of the posterolateral thalamus. Visual, auditory and somatosensory stimuli were paired in various combinations: V-A, S-V, V-A, A V, S-A and A-S. In each case the amplitude of the response to the second stimulus was determined as ISis decreased. Amplitude was measured from peakto-peak for the first positive and negative waves only, and does not include any later secondary components which are often variable and affected by a preceding stimulus at much greater ISls. For comparative and graphical purposes the amplitude of the response to the second stimulus, when presented alone, was used as a control and

A

B

taken as 100%. The amplitude of the response to the second stimulus, when preceded by a response to a stimulus of another modality, was expressed as a percentage of the control response and plotted as a function of the ISI. Figs. 5 and 6 show typical results when a predominantly visual responsive site in the postero-lateral pulvinar (A 4.5, L 7.0, H+6.0) was studied using various combinations of stimulus pairs separated by varied ISis. It may be noted that there is a distinctive evoked potential form and amplitude for each modality from the recording site in the pulvinar. The response to the somatic stimulus, when preceded by the response to a visual stimulus (Fig. 5, A), maintained its amplitude fairly well until an ISI of 430 msec was reached; thereafter its amplitude diminished sharply to about 40 % at an ISI of 130 msec (see also left graph of Fig. 6, solid triangles). In contrast, the response to the visual stimulus, when it followed the somatic stimulus (Fig. 5, B), showed only a

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MSEC Fig. 6. Intermodalityinteractionsfor paired stimuluscombinationsinvolvingvisual,auditoryand somaticstimuli.Graphical presentation of data from Fig. 5. See text for explanationand details. 10-20~o attenuation even at an ISI of 130 msec (see Fig. 6, left graph, open triangles). Similarly, Fig. 5, C and D show that the visual stimulus interfered more with the response to a following auditory stimulus than vice versa (see also middle graph of Fig. 6). Thus in this postero-lateral region of the pulvinar the visual stimulus and its response had a more dominant suppressing influence upon the responses to succeeding stimuli of the other sense modes than did auditory or somatosensory responses have upon succeeding visual responses. Fig. 5, E and F illustrate that both somatic and auditory stimuli have an effect upon the responses of the other, but the auditory had a more profound influence upon somatic responses than vice versa (see also right graph of Fig. 6). The intermodality interactions were studied also in some parts of specific relay nuclei of the thalamus (lateral and medial geniculate), other non-specific association nuclei (N. lateralis and N. suprageniculatus) and other regions of the pulvinar (antero-medial; A 7.5, L 7.8, H + 6.0). In regions where mapping revealed a strong response site for a given modality (for example in the postero-lateral pulvinar for visual stimuli), a stimulus of that modality preceding one of another modality had a marked suppressive effect upon the latter and in turn was more resistant to suppression by other sensory stimuli. Auditory stimuli tended to have a larger response than visual or somatic stimuli in regions surrounding the principal part of the medial geniculate nucleus (magnocellular part and N. suprageniculatus) and in general the auditory responses were less suppressed by intermodality

interaction than in more remote regions. In specific relay nuclei themselves (MG and LG), under chloralose anesthesia, the primary evoked response to stimuli of the corresponding modality predominated and was affected very little by a preceding stimulus of another modality; furthermore, the stimulus specific to that relay nucleus tended to suppress markedly the responses to stimuli of the other modalities which followed it. V. Micro-electrode recordings .from posterolateral thalamic nuclei

In the unanesthetized brain of 12 cats under Flaxedil and local anesthesia single unit responses to visual flash stimuli were recorded from representative regions of the pulvinar, N. posterior, N. lateralis posterior and N. suprageniculatus. These were preliminary investigations for the purpose of sampling activity in certain regions where gross electrode mapping had been done. Another purpose was to relate the onset, duration and pattern of unit discharge to the components of the evoked response in the primary visual cortex. Several types of unit responses were discovered in more than twenty regions examined. Although by no means a definitive study, some of the types of unit or grouped unit discharges are shown in Fig. 7. Figs. 7, A and B, respectively, illustrate unit responses from postero-lateral (A 4.0, L 7.6, H 7.2) and postero-medial (A 4.0, L 5.3, H 4.9) pulvinar together with evoked responses from visual cortex (A 2, L 4). Fig. 7, A shows a multiple spike discharge with an onset latency of 25-35 msec and a duration of about 50 msec. The

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Fig. 7. Micro-electrode recordings from pulvinar and adjacent regions of postero-lateral thalamic association nuclei in unanesthetized brain {Flaxedil). Responses evoked by single photoflash stimuli at 7 sec intervals. Recording sites : A : posterolateral pulvinar; B: postero-medial pulvinar; C: antero-lateral pulvinar; D: antero-medial pulvinar; E: N. posterior; F and G : margin of pulvinar and N. suprageniculatus--G, one-tenth m m lower. Upper trace in records A, B and E is from visual cortex. See text for details. Stimulus at upward or downward stimulus artifact deflection. Calibrations: 100/~V, 100 m sec.

latency and duration of the discharge corresponded well with the initial positive wave of the pulvinar response recorded with macroelectrodes from this region. The initial positive wave of the evoked response on the visual cortex occurred before the onset of the unit burst, but the secondary components corresponded in time with the unit discharge in the pulvinar. Unlike the unit discharge of the postero-lateral pulvinar in Fig. 7, A which has a short latency and long duration, the unit response from the postero-medial pulvinar (Fig. 7, B) showed only a long latency, brief burst of

3 6 spikes, The onset latency of 140-150 msec corresponded essentially with the peak of the negative after-potential recorded in this region of the pulvinar with macro-electrodes. The entire unit discharge occurred during the descending phase of the negative after-potential of the response on the visual cortex. Fig. 7, C and D present unit responses from antero-lateral (A 6.5, L 8.1, H 6.2) and anteromedial (A 7.0, L 6.3, H 6.9) pulvinar, respectively. The interesting feature of the unit responses in these two locations, where grossly recorded responses were less prominent to visual flash

276 stimuli than in the postero-lateral region, is that there were two brief bursts of spikes as a rule, one of short latency (50-60 msec) and one of long latency (325 msec) in the antero-lateral region and of 40-50 msec and 430 msec in the antero-medial region. Fig. 7, E shows single unit recordings from N. posterior (A 6.0, L 8.4, H 5.0) to a singlc flash, together with the visual cortical response. The unit always responded with a single spikc of long latency (110-140 msec). It occurred just before the peak of the positive response on the cortex and its latency corresponded to the peak of a long and late positive component of the macro-electrode response in N. posterior. Fig. 7, F shows rhythmic bursts of unit discharges recorded in N. suprageniculatus (A 4.5, L 6.3, H 4.3); Fig. 7, G was recorded from a different type of unit 0.1 mm lower in the same region. The periodic bursts of Fig. 7, F suggest a rhythmically recurring process of excitation and inhibition at a rate of about 6/sec. The unit shown in Fig. 7, G had a moderately high rate of firing prior to stimulation, was inhibited by the flash, then gave a short burst and was again inhibited, after which it began to fire continuously at a rate higher than prior to stimulation and with some tendency for periodic interruptions. Obviously much more extensive study by micro-electrode methods will be required to define and characterize the types of unit activity found throughout the postero-lateral thalamic association nuclei. However, the samples presented indicate considerable diversification. The periodic bursts found in the region of N. suprageniculat us suggest that it may be a synchronizing system of the type postulated by Andersen and Andersson (1968). DISCUSSION

Systematic mapping of evoked responses in the pulvinar and related postero-lateral thalamic nuclei has revealed widespread responsiveness to visual, auditory and somatosensory stimuli in the unanesthetized brain as well as under chloralose anesthesia. The responses vary regionally in magnitude, latency, recovery cycle time and intermodality interaction, both within the pulvinar and in the

C. C. HUANG AND D. B. LINDSLEY

broader region of the postero-lateral nuclei. A micro-electrode sampling of units to visual stimulation only, though only preliminary in nature, confirmed that there were regional differences in the types of unit responses encountered in different areas. The fact that all three stimuli produced widespread responses in the area, and particularly in the pulvinar, suggests that it is a polysensory convergence center, as are certain other thalamic nuclei such as N. centrum medianum (Albe-Fessard and Rougeul 1958). However, the centrum medianum appears to be concerned with integration of sensorimotor activities, whereas the pulvinar and related nuclei seem to be more involved in sensorysensory integrative activity. The latter is suggested partly by the intermodality interaction results and partly by the regions of the cortex to which the pulvinar and related nuclei project and from which they are believed to receive projections. It seems clear that the convergent but widespread responses in the pulvinar and associated nuclei are not due to electrical spread or volume conduction from the relay nuclei themselves. The responses were different in pattern and time course from those recorded in specific relay nuclei and latencies were considerably shorter in the specific relay nuclei. Furthermore, the recovery cycle and intermodality interaction results indicate that in, or near, specific relay nuclei there was a more rapid recovery and less suppressive intermodality interaction than in the association nuclei proper. The polysensory responses observed in relay nuclei, e.g., auditory and somatosensory in lateral geniculate, and visual and somatosensory in medial geniculate are not due to chloralose for they also occur in the unanesthetized brain. Such responses are different from those evoked by the sense mode appropriate to the relay nucleus concerned and they are different in form and polarity from those in the pulvinar and related association nuclei. Cross modality influences of this sort have been observed by others (Hotta and Kameda 1963; Papaioannou 1969; Skrebitsky 1969) and are believed to be of non-specific, reticular origin. The mapping, recovery cycle and intermodali-

EVOKED POLYSENSORY RESPONSES IN PULVINAR

ty experiments all provide evidence that the visual modality was more effective and its responses more dominant throughout these association nuclei than were those of the auditory and somatosensory modalities; this was particularly true with respect to the pulvinar. In this connection Bental and Bihari (1963) noted that visual stimuli were more effective than auditory stimuli in eliciting unit responses in the middle suprasylvian gyrus of unrestrained, unanesthetized cats, and Bruner (1965) found "nonprimary" or non-specific visual projections from pulvinar and N. lateralis posterior to this region of the cortex. Recent years have revealed much more widespread representation of sensory responses, both specific and non-specific, over the cortex and elsewhere in the brain. Albe-Fessard and Rougeul (1958), Buser et at. (1959), Buser and Imbert (1961), Thompson et al. (!963), and others have demonstrated further evidence of diffuse representation of sensory modalities upon the cortex far beyond classical boundaries. The pathways for such influences are uncertain but Buser and Bignall (1967), have discussed this extensively in a recent review and have emphasized the importanoe of the pulvinar and lateralis posterior nuclei in the relay of photic input to visual association cortex. In agreement with this are observations on photic response enhancement in visual cortex following tetanization in the pulvinar lateralis posterior complex (gong 1959; Battersby and Oesterreich 1963; Brown and Marco 1967). Rose and Lindsley (1965, 1968), have shown in the kitten that a long latency response to light flash of non-specific cortical representation is not abolished by lateral geniculate lesion, but is abolished by lesion of the brachium of the superior colliculus or lesion of the pretedtal area and superior colliculus. Among the possible pathways mediating this non-specific response are fibers from superior colliculus and pretectal nuclei to these very association nuclei of the posterior thalamus (Altman and Carpenter 1961) whose polysensory responses have been reported here. Chalupa et al. (1972) have also dealt with sources of visual input to the pulvinar. Finally, comment should be made about the pulvinar and its related postero-lateral associa-

277 tion nuclei as sensory convergence and interaction centers and the potential role that such centers may have with respect to attention and discrimination functions. Bental and Bihari (1963) contrasted the relative absence of convergence of sensory inputs upon units in the primary somatic sensory area of the cat's cortex (Mountcastle 1957) with the high degree of convergence they found on single units in the middle suprasylvian association cortex in the cat. They suggested that this functional difference between primary cortex units and association cortex units might permit modality discrimination by the former and only interaction between modalities in the latter. In connection with the results of the present study, macro-electrode recording revealed regional differentiation with respect to visual, auditory and somatosensory stimulation, although in general all regions of the pulvinar were in some degree responsive to each sense mode. Perhaps more importantly, intermodality interaction tests revealed differences also. In regions of the pulvinar where a given modality evoked a larger amplitude and shorter latency response, the response to a stimulus of that mode dominated in the intermodality interaction tests. For example, in the postero-lateral region of the pulvinar visual responses dominated. A visual stimulus preceding an auditory or somatosensory stimulus had a more profound effect upon either than vice versa. Although dominated by visual stimuli, auditory stimuli were dominant over somatosensory stimuli. These regional and intermodality interaction differences would seem to provide a potential code for attention and discrimination so that in the visual region of the pulvinar the hierarchy of precedence would be in the order visual, auditory and somatosensory. In the auditory region the order of dominance would be auditory, visual and somatosensory. Although all three stimuli may have access to a given region, an order of dominance would favor selective attention and discrimination. On the other hand such regional or spatial codes might be superceded by temporal codes imposed by influences from other systems, either specific or nonspecific sensory systems, whose pacemaker or synchronizing influences might shift the action

278 from one region to another and in so doing shift the balance of influence of the pulvinar (and possibly other association nuclei of the lateral nuclear group) upon the cortical area to which it projects. In man this would be the critically important integrative center at the junction of the occipital, parietal and temporal lobes, usually designated as the supramarginal and angular gyri and sometimes identified as part of Wernicke's area. SUMMARY

Mapping of evoked responses in the pulvinar and adjacent nuclei of the thalamus in the cat under chloralose anesthesia and in the unanesthetized brain (Flaxedil and local anesthesia) was carried out for visual, auditory and somatosensory stimuli. Results have revealed that this region is a polysensory convergence center since all three sense modes produced responses which were widely distributed, although in a regionally differentiated fashion. Visual responses were more prominent in the postero-lateral region than in other regions of the pulvinar or than in other association nuclei. Similarly auditory and somatosensory responses, though overlapping in their spatial distributions, showed a magnitude differential in certain regions, usually those closest to the specific relay nucleus of the particular modality concerned. The nature and distribution of the responses under chloralose and in the absence of general anesthesia (Flaxedil and local anesthesia) were similar but the responses were larger and of longer latency under chloralose. In addition to the mapping of responses a comparison of the latencies was carried out, as well as recovery cycle and intermodality interaction tests. The latency and recovery cycle results tended to confirm the regional differentiation observed in the mapping studies. In the intermodality interaction tests visual stimuli were found to be dominant over auditory and somatosensory stimuli in postero-lateral pulvinar, and auditory stimuli were dominant over somatosensory stimuli. This latter result is discussed in terms of its implications for attentional and discrimination coding of sensory stimuli.

C. C. H U A N G AND D. B. LINDSLEY

Preliminary micro-electrode studies revealed certain temporal correspondences between unit discharges and evoked potentials in the pulvinar, as well as with the secondary or late waves recorded in the visual cortex. RESUME REPONSES POLYSENSORIELLES ET INTERACTION SENSORIELLE DANS

LE

PULVINAR

ET

LES

NOYAUX

THALAMIQUES POSTERO-LATERAUX DU C H A T

L'6tablissement de la carte des r6ponses 6voqu6es dans le pulvinar et les noyaux adj acents du thalamus chez le chat sous anesth6sie au chloralose et darts le cerveau non anesth6si6 (Flax6dil et anesth6sie locale) a 6t6 effectu6e pour les stimuli visuels, auditifs et somato-sensitifs. Les r6sultats ont montr6 que cette r6gion est un centre de convergence polysensorielle puisque ces trois modalit6s sensorielles provoquent des r6ponses qui sont largement distribu6es, bien que d'une mani6re r6gionalement diff6renci6e. Les r6ponses visuelles sont plus pr6dominantes dans la r6gion post6ro-lat6rale que dans les autres r6gions du pulvinar ou que dans les autres noyaux d'association. De m~me les r6ponses auditives et somato-sensitives, bien que se chevauchant dans leur distribution spatiale, montrent une diff6rence d'amplitude dans certaines r6gions, habituellement celles qui sont les plus proches du noyau de relai sp6cifique de la modalit6 sensorielle concern6. La nature et la distribution de ces r6ponses sont similaires sous chloralose et en l'absence d'anesth6sie g6n6rale (Flax6dil et anesth6sie locale), mais les r6ponses sont plus grandes et de plus longue latence sous chloralose. Outre la carte des r6ponses, il a 6t6 proc6d6 une comparaison des latences, de m~me qu"fi des tests de cycle de r6cup6ration et d'interaction intermodalit& Les r6sultats concernant la latence et le cycle de r6cup6ration tendent ~ confirmer la diff6renciation r6gionale observ6e dans les &udes topographiques. Dans les tests d'interactionintermodalit6, les stimuli visuels se sont r6v616s ~tre pr6dominants sur les stimuli auditifs et somato-sensoriels au niveau du pulvinar post6rolat6ral, et les stimuli auditifs ~tre pr6dominants sur les stimuli somato-sensitifs. Ce dernier r6sultat est discut6 en fonction de ses implications en

EVOKED POLYSENSORY RESPONSES IN PULVINAR

ce qui concerne le codage d'attention et de discrimination des stimuli sensoriels. Des 6tudes pr61iminaires par micro-61ectrodes montrent certaines correspondances temporelles entre les d6charges unitaires et les potentiels 6voqu6s dans le pulvinar de m~me qu'avec les ondes secondaires ou tardives enregistr6es dans le cortex visuel.

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WALKER s A.