Activity of single neurons in the monkey amygdala during performance of a visual discrimination task.

JOURNALOFNEUROPHYSIOLOGY Vol. 67, No. 6, June 1992. Printed

in U.S.A.

Activity of Single Neurons in the Monkey Amygdala During Performance of a Visual Discrimination Task KATSUKI

NAKAMURA,

AKICHIKA

MIKAMI,

AND

KISOU

KUBOTA

Department of Neurophysiology, Primate Research Institute, Kyoto University, Inuyama, Aichi 484, Japan relatedto the recognitionand/ or the evaluation of complex visual stimuli. Selectivevisualand delay neuronsmay be associated with short-term storage of visual information. However, nonselective from the monkey amygdala while monkeys performed a visual discrimination task. The monkeys were trained to remembera visual neurons,aswell asnonselectivedelay neurons,may be revisualstimulusduring a delay period(0.5-3.0 s), to discriminatea lated to the anticipation of a visual stimulus or may reflect the newvisual stimulusfrom the stimulus,and to releasea lever when monkey’s level of attention. Our data suggestthat the monkey the new stimuluswas presented.Colored photographs(human amygdalamay be involved in the recognition and/or evaluation faces,monkeys, foods, and nonfood objects)or computer-gener- of complex stimuli, and it may play a role, though relatively ated two-dimensionalshapes(a yellow triangle, a red circle, etc.) minor, in the short-term storageof complex visual stimuli. were usedasvisual stimuli. 2. The activity of 160 task-related neurons was studied. Of these, 144 (90%) respondedto visual stimuli, 13 ( 8%) showed INTRODUCTION firing during the delay period, and 9 (6%) respondedto the reIn contrast to the earlier view that the monkey amygdala ward. is involved in emotional or autonomic responses (Goddard 3. Task-relatedneuronswerecategorizedaccordingto the way in which various stimuli activated the neurons.First, to evaluate 1964; MacLean 1949, 1952), several sets of behavioral obthe proportion of all testedstimuli that elicited changesin activity servations suggest that the primate amygdala is involved in of a neuron, selectivity index 1 (SI 1) was employed. Second,to higher cognitive functions (Andersen 1978; Gloor et al. 1982; Sarter and Markowitsch 1985). In evaluatethe ability of a neuron to discriminate a stimulusfrom 198 1; Mishkin anotherstimulus,S12wasemployed.On the basisof the calculated particular, it is claimed that neurons in the amygdala envalues of SIl and S12,neurons were classifiedas selectiveand code the biological value of sensory stimuli from the externonselective.Most visual neurons were categorized as selective nal world and from within the body ( LeDoux 1987 ) . Bilat( 131/ 144)) and a few were characterized as nonselective( 13/ eral removal of the monkey amygdala leads to a variety of 144). Neurons active during the delay period were alsocatego- behavioral changes, such as hyperemotionality, meat eatrized asselectivevisualand delay neurons( 6/ 13) and asnonselecing, coprophagia, excessive exploration, psychic blindness, tive delay neurons( 7 / 13) . 4. Responses of selectivevisual neuronshad various temporal etc. (Aggleton and Passingham 198 1; Dicks et al. 1969; and stimulus-selectiveproperties.Latenciesrangedwidely from Goddard 1964; Horel et al. 1975; Kling and Steklis 1976; 60 to 300 ms. Responsedurations alsorangedwidely from 20 to Rosvold et al. 1954; Thompson et al. 1977; Weiskrantz 870 ms. When the naturesof the various effective stimuli were 1956). These behavioral changes can be explained for the studiedfor eachneuron, one-fourth of the responses of theseneu- most part by the hypothesis that such lesions interrupt the ronswereconsideredto reflect somecategoricalaspectof the stim- connections between the inferotemporal cortex and the uli, such as human, monkey, food, or nonfood object. Further- amygdala (Geschwind 1965; Weiskrantz 1956). more, the responses of someneuronsapparentlyreflecteda certain Previous single-neuron studies in the monkey showed behavioral significanceof the stimuli that was separatefrom that rates of discharges from amygdalar neurons changed in the task, such asthe face of a particular person,smiling human response to simple as well as complex visual stimuli, such as faces,etc. simple colored lights (Fuster and Uyeda 197 1 ), human 5. Nonselectivevisual neuronsrespondedto a visual stimulus, regardlessof its nature. They also respondedin the absenceof a faces (Leonard et al. 1985; Rolls 1984), and real foods and visual stimuluswhen the monkey anticipated the appearanceof objects (Nishijo et al. 1988a,b; Ono et al. 1983; Sanghera et al. 1979 ) . All these studies used relatively limited kinds and the next stimulus. 6. Selectivevisualand delay neuronsfired in response to partic- numbers of visual stimuli, and all these visual stimuli were ular stimuli and throughout the subsequentdelay periods.Nonse- shown to monkeys under conditions such that each stimulective delay neuronsincreasedtheir dischargeratesgraduallydur- lus had a particular behavioral significance. For example, a ing the delay period, and the dischargerate decreasedafter the food was a positive discriminative stimulus and the monnext stimuluswaspresented. key was rewarded when he responded to the stimulus, 7. Task-relatedneuronswereidentified in six histologicallydis- whereas a syringe was a negative discriminative stimulus tinct nuclei of the amygdala.Selectivevisual neuronsweremainly located in the dorsalpart of both the lateral and the lateral basal and a response to it was not rewarded. Therefore it was nuclei, which receiveafferent projectionsfrom the inferotemporal unclear whether the changes in activity were caused by the visual stimulus itself or were due to the behavioral significortex. 8. Probably, selectivevisual neuronscan receive visual infor- cance of the stimulus in the tasks that the monkeys permation from the inferotemporal cortex, and theseneuronsmay be formed. To examine the properties of visual responses of SUMMARY

AND

CONCLUSIONS

1. The activity of singleneuronswasrecordedextracellularly

0022-3077/92 $2.00Copyright 0 1992The AmericanPhysiological Society

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A. MIKAMI,

single amygdala neurons, we considered it necessary to survey stimulus-selective properties of amygdalar neurons during responses to a variety of visual stimuli that have little behavioral significance within a task. Recent studies of lesioned monkeys during performance of delayed nonmatching-to-sample tasks have led to the hypothesis that the functions of the monkey amygdala are related to learning and short-term memory (Mishkin 1982; Murray 1990). Combined lesions of the bilateral amygdala and hippocampus (Mishkin 1978; Saunders et al. 1984) or of the bilateral amygdala and rhinal cortex (Murray and Mishkin 1986) produced severe deficits in the performance of the task. By contrast, Zola-Morgan et al. ( 1989) recently reported that lesions of the amygdala alone, without damage to the adjacent cortex, did not impair performance of the task, suggesting that the monkey amygdala does not contribute to short-term storage of visual information. Lesion studies do not, however, provide information about the function of the intact amygdala. Because there have been, to our knowledge, no recording studies aimed at examining the role, if any, of the amygdala in visual shortterm memory, we chose to study the activity of amygdalar neurons in the context of short-term memory. In the present study, we recorded the activity of single neurons in the amygdalas of three rhesus monkeys during the performance of a visual discrimination task, a modified version of a delayed nonmatching-to-sample task that required remembering a visual sample stimulus that was presented repeatedly on a display during a delay period, and then discriminating a new stimulus from the sample stimulus. With this task, designated as a sequential visual discrimination task with a time delay, we found that some amygdalar neurons selectively responded to particular stimuli that had a certain behavioral significance outside the task. A preliminary version of this work has been presented elsewhere (Nakamura et al. 1989a,b, 1990).

AND K. KUBOTA

eating the monkey’s correct response.The task wasdesignateda sequentialvisual discrimination task with a time delay. The experimentalsetupusedin this study isillustratedin Fig. 2. Each componentis describedin the numerical order given by the numbersin circlesin the figure. 1) A coloredphotographstoredin a videodisc player (LV-200; TEAC, Tokyo, Japan) or a two-dimensionalshapegeneratedby personalcomputerB ( PC9801VM; NEC, Tokyo, Japan) was presentedas a visual stimulus on the monitor. Only l-3 mswere necessaryfor presentationof a stimulus on the screenafter a commandwasgiven to the computer. 2) Neuronal activity wasamplified with a homemadepreamplifier and an amplifier (R5 103N;Tektronix, Beaverton, OR, USA) and wasconverted into pulseswith a window discriminator (DIS- 1; Bak Electronics,Germantown, MD, USA). Then the timing of eachpulsewasstoredon a floppy disk by computerB. 3) Timing of task-relatedevents, such asdelivery of the reward and the monkey’spressingand releasingthe lever, werealsostoredon the same floppy disk. 4) For on-line analyses,the neuronalactivity wassent to personal computerA (PC9801VM; NEC, Tokyo, Japan) to monitor dischargepatternsthat were representedasperistimulus time histogramson a display.5) The monkey’seyepositionswere measuredwith a magnetic search-coilunit (MEL-20; Enzanshi, Tokyo, Japan) and were monitored on the samedisplay. 6) Eye positionswere superimposedon the visual stimulusat which the monkey waslooking and were storedon the videotapeof a video recorder( NV-DS 1; Matsushita, Osaka,Japan). The monkey wastrained for 1-2 mo to perform the task at a correct performance level of 90%. The monkey repeatedtrials 600-1,200 times a day. The mean reaction times (the time between the onsetof the R and the releaseof the lever by the monkey) in daily sessions rangedfrom 350to 600 ms.The monkey was returned to his own cageafter the day’straining or recording sessions. Each monkey washousedindividually in his home cageand suppliedwith food ad libitum. He wasdeprived of water in his cageand obtained water asa reward during training or recording sessions. Supplementalwater and fruit weregiven asneededafter eachday’s session.To maintain the monkey’s health, his weight wasroutinely monitored. This experiment wasperformed under

Sl

Sn

s2

R

METHODS

Behavioral task and experimental setup Three young male rhesusmonkeys(Macaca mulatta), weighing 4.5-6.5 kg, were used.The monkey sat in a primate chair, facing a 2l-in. multiscan TV monitor (PC-TV47 1; NEC, Tokyo, Japan). He performed a visual discrimination task by manipulating a lever (6 11T; Tateishi, Kyoto, Japan) attachedto the chair in front of him at lumbar level. When the monkey pressedthe lever, a trial was started. The monkey kept pressingthe lever throughout a trial. Figure 1 illustrates schematicallythe temporal sequenceof events in a single trial. After a waiting period (W) of 1.Os,the first samplestimulus ( S1) waspresentedfor 0.5 or 1.Os (St, fixed in eachsession)on the screenof the monitor. After a delay period (D, fixed within each session)of 0.5-3.0 s,the samesamplestimulus(S2) waspresented again.This stimulus-delaysequencewasrepeated.The number of repetitions of the samplestimulus( 1-4; Sn) wasselectedquasirandomly from trial to trial to avoid habituation to the task on the part of the monkey and to lower the chancelevel of performance. Then a new R waspresented.A liquid reward was given to the monkey when he releasedthe lever within 1.Os of the presentation of the R. The delivery of a reward wasaccompaniedby a slight soundof a solenoidand a sound from a personalcomputer indi-

Sample stimulus Response stimulus Reward

Lever

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III

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1

I i I1 i

..I

-1

I

i W iSt! D I i i i i

Abbreviations: W, Waiting D, Delay

period period

:Rw i

(1.0 s); St, Stimulus-on (variable,

0.5-3.0

period

s); Rw, Reward

(variable,

0.5-1.0

s);

period

FIG. 1. Temporal sequence of a trial of the sequential visual discrimination task with a time delay (a modified version of the delayed nonmatching-to-sample task). Each trial was started by the monkey’s pressing a lever. The monkey kept pressing the lever until a R was presented. After a waiting period (W) of 1.0 s, the first sample stimulus (Sl ) with a delay period (D) of 0.5-3.0 s was presented on the screen of a TV monitor. The same sample stimulus was repeatedly presented between 1 and 4 times (Sn), then a new R was presented. If the monkey released the lever within 1.0 s of the onset of the R, a liquid reward was administered into his mouth. “Lever” means that the monkey pressed the lever.


VISUAL

0

I ’ Personal

computer

A

AC/DC

Personal

7

Converter

Search-coil

63 Superimposing

Video Videodisc

RESPONSE PROPERTIES

unit

board

NEURONS

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anesthesia(30 mg/kg iv). A stainlesssteelcylinder for recording ( 19 mm diam) and a head-holdingdevice wereimplanted on the skull. An eyecoil (Judgeet al. 1980)wasalsoimplantedbelowthe conjunctiva of oneeye.Postoperatively,antibioticswereadministered for > 1wk intramuscularlyto protect the monkey from bacterial infections. After a recovery period of > 1 wk, recording sessionswere started.

recorder

Recording and analysis of data

player

computer

OF AMYGDALAR

B

Parallel

I/D

discriminator

2. Schematic drawing of the experimental setup. The monkey sat in a primate chair facing the screen of a TV monitor. Numbers in circles ( l-6) indicate the passage of information through the lines. 1: visual stimuli-a colored photograph or a 2-dimensional shape was presented on the screen as a visual stimulus. 2: neuronal spike activity-neuronal activity was amplified, converted into pulses, and stored on the floppy --_ disk of personal computer B. 3: task event signals-signals corresponding to delivery of the reward, pressing of the lever, and release of the lever were also stored on the floppy disk. 4: neuronal activity-neuronal activity was sent to personal computer A for on-line analysis.- 5: monkey’s eye positionseye positions were measured with a search-coil system and were monitored on a display. 6: visual stimuli and eye positions-visual stimuli and eye positions were superimposed and were stored on a videotape. The arrowhead on the monkey’s head indicates a microelectrode. FIG.

the “Guidelines for Care and Use of Laboratory Animals” from the National Institutes of Health ( 1985) and with referenceto the “Guide for Care and Use of Laboratory Primates” publishedby our Institute ( 1986).

Visual stimuli Sampleand R were selectedfrom -800 color photographs (facesof membersin our Institute, facesand bodiesof monkeys within and outsideour Institute, foods,and nonfood objects)and from - 100 two-dimensionalshapes(a yellow triangle, a green square,a white circle, etc.). All photographs,except for thoseof monkeysin an open field, had a uniform background (sky-blue screen).Eight pairsof sampleand R constituteda stimulussetand were presentedto the monkey while the neuronal activity was recorded.The eight pairsin a setwerepresentedin quasi-random orderand wereusedmorethan four times,sothat >32 trials could be recordedfor eachstimulusset.A block consistingof >32 trials with a stimulusset wascalled a session.We classifiedthe photographsinto four stimulus categories,namely human face, monkey, food, and nonfood object. In total, 45 stimulus setswere prepared:human faces(yt = 18 stimulussets), such asthe front view of a face, the sideview of a face, faceswith various facial expressions,and variousviews of the faceof one person;monkeys (y1= 16), suchasmonkeysin a field, the front view of a monkey’s face, a monkey’sfacewith various facial expressions,and various views of the face of a particular monkey and a chimpanzee; various objects(yt = 7)) namely, various foods(an apple, an orange,a sweetpotato, etc.), various nonfood objects (a primate chair, a water bottle, a camera,nuts and bolts, a syringe,etc.), and various coloredtwo-dimensionalshapes( YI= 4).

Surgical procedures When a monkey reacheda criterion of >90% correct responses for >l wk, surgery was performed under pentobarbital sodium

During recordingsessions, the monkey wasseatedin a primate chair with his head tightly fixed to the chair frame. A hydraulic microdrive (MO-g; Narishige,Tokyo, Japan) wasattachedto the recordingcylinder and wasadvanced.The activity of singleneuronswasrecordedwith a glass-coated cobalt-nickelalloy (Elgiloy) microelectrode( 5-7 MQ, 1.O-1.2 mm diam) or a polyurethanecoatedtungstenmicroelectrode( 5-7 MQ, 0.3 mm diam). To insert a tungsten microelectrodethrough the dura matter without distortion, a stainlesssteelguidetube ( 1.1 mm diam) waslowered to - 15mm belowthe surfaceof the dura. Approximate locations of microelectrodesrelative to the bony landmark were measured from radiographstaken during selectedexperimental sessions. The posterior tip of the sphenoidbone was usedas a landmark situatedat a constant anterior-posteriordistancefrom the amygdala ( Aggleton and Passingham1981) . We sampledthe neuronal activity only if the height of the peak of the spikewasthree times greater than the noiselevel ( 150-400 pV). The spike of a single neuronwasisolatedfrom thoseof other neuronsby its magnitude and negative shape.In most cases,the largestneuronalspikewas isolatedwith the window discriminator by its size. Occasionally, spikesof two neurons were of similar magnitude, and in those caseswe isolatedone from the other by referenceto the waveforms. While we were penetrating an electrodeand searchinga responsiveneuron, we continuously presentedone of three basic stimulussetsconsistingof eight pairsof stimuli, that is, one “human face” set, one “monkey” set or one “object” set. When a neuron respondedto one of the three sets,we extensively tested other stimulussetsconsistingof stimuli of the samecategory. If the testedneuron appearedto showchangesin activity that were related to the task event, asjudged from the dischargepatterns representedasperistimulustime histogramson the display (personalcomputerA in Fig. 2) that wasusedfor on-line analysisand from listeningto the spikeoutput on a speaker,the activity of the neuron wasextensively testedand wasincorporatedinto the data base;neuronsfound to be unresponsiveto three or four setsof stimuli during preliminary testswere not further testedand were not included in the data base.The spikewassampledat intervals of 1ms.Throughout recordingsessions, the shapesof the neuronal spikeswere monitored with a dual-beam display unit (D12, R5 103N; Tektronix, Beaverton, OR, USA) to confirm that only the activity of a given singleneuron wasbeing sampledand recorded. At selectedsiteson selectedrecording tracks, an anodal current (0.5-10 PA, 15-120 s) waspassedthrough the microelectrode (Elgiloy or tungsten)to makean electrolytic microlesion. Off-line analyseswere performed with the personalcomputers designatedA and B in Fig. 2. Averaged perievent time histograms and raster displays were made from the data stored on floppy disks.The averagerate of discharges during the latter half (0.5 s) of the waiting periodbeforethe first samplestimulus(S 1)) definedas the control period, wascalculatedand taken asthe control rate. Perievent time histogramstriggered by the various task events (onsetsof sampleand R, releaseof the lever, and delivery of the reward) were computed(binwidth 10 ms). Then the ratesof dischargesduring variousperiodsof the taskwerecomparedwith the control rate. We analyzedchangesin activity during the stimulus-onperiod asfollows.Averagedperistimulustime histogramswerecomputed


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K. NAKAMURA,

A. MIISAMI,

with respectto the onset of the first stimulus (S 1) for all tested stimuli for eachneuron. From the histogramsfor eachneuron, the histogramwith the highestpeak value waschosen.In the highestpeak histogramderived from the responses to the most effective stimulus,the startingpoint of the changein activity (time at which the 1st of consecutivebinsdiffered from the control rate by 22 SD; normal distribution, P < 0.05) and the end point (time of the last bin) were measured.If a neuron wasassociatedwith changesin activity throughout the stimulus-onperiod, and if thesechanges continued during the delay period, the end of the stimulus-on period ( 1.Os after the onsetof the stimulus)wastaken asthe end point of changesin activity in responseto a visual stimulus.The time from the onset of the stimulus to the starting point of the changein activity wastaken asthe onsetlatency. During performanceof the task, we allowedthe monkey to move his eyesfreely so that he could look at various parts of eachstimulus.Thus the latenciesmeasuredhere were relative and not absolute,that is, they weremeasuredfrom the onsetof the visual stimulusand not from the time of monkey’slooking at the stimulus,suchasfoveation. The time from the starting point to the end point of changes in activity was regardedas the time during which the changes continued and was designatedthe responseduration. Then the distribution of the number of spikesper lo-ms bin, but not the numberof spikesitself, from the start point to the end point were comparedwith the distribution of the number of spikesper lo-ms bin during the control period by a statisticalmethod(Mann-Whitney’s U test). If the two distributions were significantly different (P < 0.05), we concluded that the stimulus elicited changesin activity of the neuron and that the neuron wasa visually responsiveneuron. Furthermore, in many cases,a singleamygdalarneuron showedthe responses of different magnitudesto different visualstimuli. For eachneuron, we attemptedto evaluatethe differential property of the changesin activity with two indexes (selectivity indexes)to indicatethe extent to which a given neuron wasselectively associatedwith changesin activity in responseto visualstimuli, i.e., stimulusselectivity. First, we attemptedto evaluatewhat proportion of all testedstimuli elicited changesin activity of a neuron. For eachstimulus,the distribution of the number of spikesper IO-ms bin from the start point to the end point, measuredfrom the responses to the most effective stimulus,was comparedwith the distribution of the numberof spikesduring the control period, and a decisionwasmadeasto whether the stimuluselicited changesin activity of the neuron or not. Then a value of selectivity index 1 (SI 1) wascalculatedfor each neuron SI 1 = 1 - ( number of effective stimuli/ number of tested stimuli)

In this equation, “effective stimuli” meansthe stimuli that elicited changesin activity of the neuron. If a neuron showedchangesin activity in responseto all visual stimuli tested, SIl waszero. If a neuron showedchangesin activity in responseto only a few stimuli, SIl was- 1. We calculatedthe valuesof SI1 for the first samplestimuli ( S1) and the responsestimuli (R) separately.However, mostneuronsshowedonly smalldifferencesbetweenthe two values.Then SI1 wascalculatedfrom the responses to S1. Second,to evaluatethe ability of a neuron to discriminatea stimulus from another stimulus,we calculated selectivity index 2 (SI2), which wasbasedon comparisonsof the magnitudeof the responses to the mosteffective stimuluswith the magnitudeof the responses to the remainingstimuli. If the responses to a stimulusweresignificantly weakerthan the responses to the most effective stimulus(MannWhitney’s U test, P < 0.05), the neuron wasconsideredto have the ability to distinguishthe stimulusfrom the most effective stimulus and the stimuluswasregardedasa distinguishablestimulus. To evaluatethis ability of a neuron, we adoptedthe next equation S12 = ( number of distinguishable stimuli)/ (number of the remaining. stimuli)

AND K. KUBOTA

If S12was 1, the neuron was consideredto have the ability to discriminatethe most effective stimulus from all the remaining stimuli. Such a neuron wasdesignateda discriminating neuron. By contrast, if S12was near zero, the ability of the neuron to discriminatethe mosteffective stimulusfrom the remainingstimuli can be regardedasvery low. Furthermore, to examinewhether or not an amygdalarneuron tendedto changeits rate of discharge in responseto oneparticular categoryof stimulus,the nature (category) of the most effective stimulus and that of the stimuli that wereindistinguishablefrom the mosteffective stimuluswerestudied for eachneuron that we could test with all four categoriesof stimulus( human face, monkey, food, and nonfood object). If all indistinguishablestimuli werein the samesinglecategory asthat of the most effective stimulus,the responses of the neuron might be consideredto representsomecategoricalaspectof the stimuli. Such a neuron wasdesignateda categoricalneuron. We studied the categoriesof the most effective stimuli of all the designated discriminatingneuronsand categoricalneurons. To studythe effectsof repetitive presentationsof the samestimulus on the magnitude of neuronal dischargesin responseto the visual stimulus, we also comparedthe magnitudesof neuronal responses to Sl or to the second,third and fourth samplestimuli by the samestatisticalmethod. For analysisof the changesin activity during the delay period, we comparedthe distribution of the number of spikesper lo-ms bin during the delay period after eachstimuluswith the distribution of the number of spikesduring the control period. To minimize the effect of afterdischargesdue to strong stimulations,the data from the first 500msof the delay periodwerenot usedfor this analysis.If the distributions of the number of spikesduring all delay periods(the first, second,third, and fourth delay periods) were significantly different from the distribution during the control period (Mann-Whitney’s U test, P < 0.05) and if the average rates were higher than the control rate, we concluded that the neuron fired during the delay periods. The changesin activity during the reward period werealsoanalyzedin a similarmanner. During recordingsessions, the monkeyssometimesmadeerroneousresponses.There were two types of erroneousresponse:a monkey occasionallyreleasedthe lever beforethe presentationof R (these errors included releaseof the lever in responseto the samplestimulus), and occasionallyhe failed to releasethe lever within 1.Os of the onsetof R. The data in theseerror trials were analyzed as needed,for example, to examine whether the given changesin activity were related to visual stimuli, the monkey’s releaseof the lever, or the reward. For two of three monkeys,patternsof fixation on visual stimuli during the performanceof the task were measuredfor 2-3 wk during the latter part of the experiment. For the calibration of the systemfor eye measurements,the monkeyswere trained to perform a visual fixation task, which wasa modified version of the visual fixation taskdevelopedby Wurtz ( 1969). In the task, when the monkey presseda lever, a pair of vertical lines (0.225” in length, with 0.075” of separation)appearedat various locations on the monitor screento adjust the gain and the offset of the search-coilsystem.After 0.5-4.0 s, the two lines changedtheir orientation from vertical to horizontal. If the monkey releasedthe lever within 0.6 s, he wasrewarded.The primate chair wasplaced in a high-frequencymagneticfield for measurements of the monkey’s eye positions (the measurementwas accurate to within 0.1”). The location of the center of the monkey’s pupil was recordedfrom its position on the screenat intervalsof 1/ 30 sduring the performanceof the task. We analyzed the monkey’sfixation patterns from the data storedon the videotapesof the video recorder(cf. Fig. 2). When the eyepositionsfell insidea circle with a diameterof 2Ofor >6 / 30 s (200 ms), we concludedthat the monkey had fixed his eyeson the position of the circle. An exampleof the natterns of a monkev’s fixation during a trial is illustrated in


VISUAL

RESPONSE PROPERTIES

Sl

s2

“I‘5 Q

Q

OF AMYGDALAR

NEURONS

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02

3. An example of monkey’s fixation patterns in response to visual stimuli in a trial. Each small dot represents a fixation point. The monkev fixated on each point for >200 ms during-. nresentation of the stimulus. The monkey fixated on points in the order that the dots are numbered ( 1, 2). FlG.

fixated on the regionsof the stimulusin the numerical order shown. In this trial, the patterns during the responsesto the first, second,and third samplestimuli were very similar. Usually, the monkey waited for a visual stimuluswith his eyesfixated nearthe center of the monitor screen,and he almost never looked away from the screenwhen a visual stimuluswas presented.

Fig. 3. The monkey

the stimulus-off period between stimuli. 3) Nine neurons

showed changes in activity during the reward period, when the monkey was rewarded after he appropriately released the lever. The remaining 248 neurons were classified as unresponsive neurons on the basis of statistical analyses. In the following sections, the discharge properties of task-related neurons are described on the basis of the timing of changes in the activity of the neurons.

Histology After all the recording sessions had beencompleted,the monkeysweredeeply anesthetizedwith pentobarbitalsodium(35 mg/ kg iv), and the brainswereperfusedwith Ringer solutionandthen with a solution of 10% Formalin or 2% paraformaldehydethat contained2% ferrocyanide for coloring the iron depositionsfrom Elgiloy microelectrodesvia the Prussianblue reaction (Suzuki and Azuma 1979). The brains were removed and cut coronally into 100~ymserialsections.Sectionswere stainedwith cresyl violet. Locations of sitesof recordingswere determined under the light microscopewith the microlesionsservingasreferencepoints. We divided the amygdalainto sevennuclei and one area,namely, the accessorybasal,the central, the cortical, the lateral, the lateral basal,the medialand the medialbasalnuclei, and the periamygdaloid area. The nuclear classificationof Crosby and Humphrey ( 1941), with the modifications derived from Price ( 1981), Amaral and Price (1984), and Iwai and Yukie (1987), was adoptedin this study. An exampleof microlesionsis given in Fig. 4, which showsa microlesionlocatedin the central nucleusof the amygdala. To study the distribution of each type of task-relatedneuron amongthe nuclei of the amygdala,the ratio of the numberof each type of neuronto the total number of the other types of neuron in eachnucleuswascomparedwith the sameratio calculatedfor the other nuclei. The x2 test was used to determine

the significance

of

differencesin this analysis. RESULTS

In total, 190 electrode penetrations

were made, and the

activity of 408 neurons was recorded from the histologically

identified amygdala of five hemispheres of three monkeys. For each neuron, on the average, 64 different stimuli were tested during the recording and four to five trials were made with each stimulus. Of these neurons, a total of 160 showed various changes in activity during three different periods of the task (task-related neurons). 2 ) One hundred forty-four neurons showed changes in activity during the stimulus-on period, when a visual stimulus was presented. 2) Thirteen neurons showed changes in activity during the delay period,

F’IG.4. An cxamplc of an electrolytic nncrolcston (4 ). The microlesion shown was made by passing an anodal current ( 10 PA, 90 ms) and was in the central nucleus of the amygdala. The 6 arrowheads indicate tracks of microelectrodes. Scale bar, 2 mm.


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A. MIKAMI,

Changes in activity during the stimulus-on period During recording sessions, we tested 114 neurons with stimuli of human faces, 118 neurons with stimuli of monkeys, 8 1 neurons with stimuli of foods and nonfood objects, and 19 neurons with stimuli of two-dimensional patterns. We successfully tested 69 neurons with all four categories of stimulus, namely, human faces, monkeys, foods, and nonfood objects. These neurons showed changes in activity of different magnitudes in response to different visual stimuli. To provide an indication of the differential property of the responses to different visual stimuli, two measures, SI 1 and S12 were employed. On the basis of the values of these two indexes, the neurons were divided into two groups: 1) one group of neurons (n = 13 1) with differential changes in activity, to a greater or lesser extent, in response to particular visual stimuli, that is, the value of SIl or S12 of these neurons was not equal to zero; and 2) a second group of neurons (n = 13) with similar (nondifferential) changes in activity in response to all tested visual stimuli, that is, the values of both SIl and S12 of these neurons were equal to zero. The neurons in the first group are designated selective visual neurons, and those in the second group are designated nonselective visual neurons. SELECTIVE VISUAL NEURONS. Of the selective visual neurons, 116 ( 89%) increased their rates of discharges ( excitatory), 7 ( 5%) decreased their rates (inhibitory), and the remaining 8 ( 6%) increased or decreased their rates depending on the visual stimulus. The magnitude of the excitatory response to the most effective stimulus and the control rate ranged, respectively, from 6.2 to 178.0 spikes/s (40.0 t 25.5 spikes/s, mean t SD, n = 117) and from 0.0 to 67.0 spikes/s (6.9 t 9.2 spikes/s). The magnitude of the inhibitory response to the most effective stimulus and the control rate ranged, respectively, from 0.0 to 0.4 spikes/s

AND K. KUBOTA

(0.03 t 0.1 spikes/s, n = 14) and from 6.8 to 47.0 spikes/s (22.3 t 12.8 spikes/s). The responses of selective visual neurons had various temporal properties. Latencies and response durations were different from neuron to neuron. The neuron in Fig. 54 had a relatively short latency ( 130 ms) and a short response duration (90 ms), whereas the neuron in Fig. 5 B had a relatively long latency ( 180 ms), and the firing continued after the stimulus was turned off, the response duration being 820 ms. Because the eyes of the monkey almost never left the monitor screen during the stimulus-on period, the transient responses in Fig. 5A are not attributable to the monkey’s looking away from the stimuli. To determine the temporal properties of visual responses, we surveyed the latency and response duration for each neuron. Figure 6A illustrates the distribution of latencies for all selective visual neurons. Latencies ranged widely from 60 to 300 ms, but 97 neurons (74%) had latencies between 100 and 200 ms ( 167 t 5 1 ms, mean t SD). Figure 6 B shows the distribution of response durations. Response durations also ranged widely from 20 to 870 ms, but those of 103 neurons (79%) were ~400 ms (260 t 242 ms). Discharge rates of 119 neurons (9 1% ) decreased to the control level during 1.O s of visual stimulation, that is, most of the amygdalar neurons showed phasic ( transient ) discharges. Selective visual neurons showed various stimulus-selective properties with respect to changes in activity. Figure 5, A and B, illustrates, for two neurons, examples of the responses to eight different sample stimuli used in one session as a stimulus set. The neuron in Fig. 5A responded to all eight stimuli (photographs of monkeys), i.e., the neuron showed relatively weak stimulus selectivity. In total, 27 out of 32 tested stimuli elicited changes in activity of this neuron. The effective stimuli included photographs of human faces, foods, and nonfood objects ( SI 1 was 0.16 ) . When the

ioosp ,/ S

i FIG. 5. Representative recordings of 2 types of discharge from selective visual neurons are shown as averaged peristimulus time histograms. A : changes in activity of a neuron with a relatively short latency ( 130 ms) and a short response duration (90 ms). All 8 stimuli elicited such changes in neuronal activity. B: changes in activity of another neuron with a relatively long latency ( 180 ms) and a long response duration ( 820 ms) . Only 1 of 8 stimuli elicited such a change in neuronal activity. Binwidth 20 ms. Neuronal discharges in response to the 8 sample stimuli used in a session are illustrated for each neuron. For each stimulus, lo- 15 trials were accumulated. A horizontal line under each histogram indicates the stimulus-on period. sPV spikes.


VISUAL

RESPONSE PROPERTIES

OF AMYGDALAR

NEURONS

1453

For each neuron tested with four categories of stimulus, we tried to determine the nature of the most effective visual stimulus, that is, whether the most effective stimulus was a human face, a monkey, food, or a nonfood object (Table 1) . More than half ( 59%) of the most effective stimuli of the discriminating and categorical neurons were photographs of monkeys, whereas the number of stimuli that consisted of a human face, as a proportion of the most effective stimuli of the two groups of neurons, was relatively low (x2 test, x2 = 5.41, P < 0.05). In most neurons, we were unable to detect any common feature among the effective stimuli. However, neuronal discharges from nine neurons ( 7%) tended to occur selectively in response to particular stimuli with a certain behavioral significance. Two neurons responded to various views of

Response

Duration

(ms)

6. The temporal properties of the neuronal responses of all 13 1 selective visual neurons. A : distribution of latencies ( 167 t 5 1 ms, mean k SD). B: distribution of response durations (260 t 242 ms). FIG.

-0 d

magnitude of the responses to the most effective stimulus (a photograph of food pellets) was compared with the magnitudes of the responses to all the remaining stimuli, the magnitude of the greatest responses could be distinguished from the magnitudes of the responses to 24 out of 3 1 stimuli (S12 was 0.8 ) . By contrast, the neuron in Fig. 5 B responded only to one out of eight stimuli (a photograph of a monkey in an open field). This neuron responded to 3 out of 64 tested sample stimuli (photographs of the monkey, a water bottle, and a camera), and the SIl value of this neuron was 0.95. The responses of this neuron to the most effective stimulus (the monkey) differed from the responses to all the remaining stimuli, that is, the S12 value of this neuron was 1.OO (this neuron was regarded as a discriminating neuron). We surveyed the SI 1 and S12 values of all selective visual neurons, and the distributions of the values of two indexes are shown in Fig. 7, A and B. As can be seen in Fig. 7A, the SI 1 values of neurons varied widely from neuron to neuron (0.60 t 0.27, mean t SD), whereas there are two peaks in Fig. 7 B, that is, the S12 values of 3 1% of neurons (4 1 / 13 1) were ~0.2, and those of 4 1% of neurons (53/ 13 1) were >0.8 (0.54 t 0.39). For 65 neurons tested with four categories of stimulus, the categories of the most effective stimulus and of stimuli that were indistinguishable from the most effective stimulus were examined to determine whether or not the neuron was a “categorical” neuron. Twenty-seven neurons were regarded as categorical neurons (including 8 discriminating neurons). These stimulus-selective properties are summarized in Fig. 7C. The SIl values of more than half of the discriminating neurons ( l ) were very high ( SI 1 > 0.8 ) , and the values of SI 1 or S12 of all categorical neurons except one (0) were very high (SI 1 > 0.8 or S12 > 0.8).

a

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Selectivity

Index

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Selectivity Index 2 FIG. 7. The stimulus-selective properties of the responses of selective visual neurons. A: distribution of selectivity index 1 (SI 1 0.60 + 0.27, mean f SD). B: distribution of selectivity index 2 (SI2,0.54 f 0.39). C: relationship between the 2 indexes. The data from 65 neurons tested with 4 categories of stimulus are presented. Each circle represents a neuron ( l , a discriminating neuron; o, a categorical neuron; o, other selective visual neuron).


1454

K. NAKAMURA,

A. MIKAMI,

AND K. KUBOTA

1. Stimuli eliciting maximal responses ,from selective caused the discharges from this neuron. The neuron was tested with photographs of various views of the bearded visual neurons

TABLE

Category of Stimulus Type of Neuron

n

Discriminating Categorical Other selective visual Total

8 19 38 65

Human 2 I 14* 17

Monkey 5 11 :i

Food 0 3 5 8

Nonfood 1 4 5 10

* Ratio of the number of the given type of neuron to the number of task-related neurons was significantly high (x2 test, P < 0.05).

the face of a particular person, one neuron responded to smiling human faces, one neuron responded to openmouth threatening faces of monkeys, one neuron responded to food pellets, one neuron responded to a human hand or a glove, one neuron responded to various views of the face of a particular monkey, one neuron responded to monkeys in an open enclosure of our Institute, and one neuron responded to a banana. All these neurons were the discriminating or categorical neurons. An example of data from a particular neuron is illustrated in Fig. 8. This neuron showed changes in activity in response only to photographs of the face of a particular human, a member of our department, but not in response to photographs of any other human faces (Fig. 8, top), monkeys, foods, or other complex objects. Some of the stimuli that failed to elicit changes in activity of this neuron were human faces with glasses or a mustache. If we look at the photographs of the various individuals, it seems unlikely that either glasses or a mustache

man’s face. This neuron changed its rates of discharges in response to all photographs of the man’s face, regardless of his orientation and facial expression (Fig. 8, bottom), and only a photograph of his back view failed to elicit the changes in activity (not illustrated). The most effective stimulus of this neuron was the man’s full face, and only the responses to his side view were indistinguishable from the responses to the most effective stimulus (32 was 0.98). This neuron responded only to seven out of 64 tested stimuli (SI 1 was 0.89), and all seven stimuli were photographs of the bearded man. Thus it is unlikely that the changes in activity of the neuron were due to some simple feature of the stimulus, such as a certain shape, color, brightness, or texture. This neuron seemed to change its rate of discharge selectively in response to the face of the bearded man. Another example is shown in Fig. 9. This neuron showed changes in activity only in response to photographs of smiling human faces. In the initial session with a stimulus set of various faces of a person, a member of our department, this neuron responded only to his smiling face. His openmouthed face was not effective. Other stimulus sets of three different people were also tested, and the neuron showed firing only in response to the smiling faces of these people. Some noneffective stimuli had a view of teeth. It is unlikely that only an “open-mouth” or “visible teeth” stimulus caused the firing of this neuron. Other stimuli, such as monkeys, foods, and nonfood objects, were also tested, but none of them generated a response from this neuron. The most effective stimulus of this neuron was the smiling face

4

ioosp, H-ii IS

FIG. 8. The responses of a categorical neuron that changed its rate ofdischarge selectively in response to views of the face of one particular person, shown as averaged peristimulus time histograms. The photograph above each histogram shows the respective stimulus. Top: comparison among neuronal responses to facesof4 different people. Bottom:comparison between responses to a single face with different orientations and facial expressions. SI 1 was 0.89, and SI2 was 0.98. For each stimulus, lo- I5 trials were accumulated. See legend to Fig. 5 for details.


VISUAL

RESPONSE PROPERTIES

OF AMYGDALAR

1455

NEURONS

IS FIG. 9. Responses ofa discriminating neuron that changed its rate ofdischarge selectively in response to a smiling human face exclusively. Comparison among neuronal responses to various facial expressions of a particular person. SI 1 was 0.98, and S12 was 1.OO.See legend to Fig. 5 for details.

in Fig. 9, and the responses to the stimulus were significantly greater than those to smiling faces of other individuals (S12 was 1.OO, namely, a discriminating neuron). This neuron appeared to change its activity selectively in response to smiling human faces. The effects of repetitive presentations of the same stimulus on the magnitude of neuronal discharges were studied. Figure 10 illustrates examples of changes in activity of three selective visual neurons. As shown in Fig. 10, A and B, the

magnitudes of the changes in activity of these neurons were similar and independent of repetitive presentations of the same sample stimulus (S 1 or the second, third, or fourth sample stimulus). However, the magnitude of the changes in activity of the neuron in Fig. 1OCdid change. The magnitude of the changes in activity of this neuron was larger in response to S 1 than the magnitudes of those in response to the other three sample stimuli (S2, S3, and S4; Mann-Whitney’s U test, P < 0.0 1). Nineteen selective visual neurons

FIG. 10. Effect of repetitive presentations of the same sample stimulus on the magnitudes of changes in activity of selective visual neurons. A and B: changes in activity of excitatory and inhibitory neurons that showed similar discharges in response to all sample stimuli (Sl, S2, S3, and S4). These neurons also showed similar discharges in response to R. C: changes in activity of a neuron that showed larger discharges in response to S 1 than in response to the other sample stimuli (S2, S3, and S4). The magnitude of discharges in response to S 1 was also larger than the magnitude ofdischarges in response to R. For each neuron, 32 trials were accumulated. See legend to Fig. 5 for details.


1456

K. NAKAMURA,

Sl

A. MIKAMI,

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b

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I

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nonselective visual neuron. a: neuronal discharges in trials with an 0.5-s stimulus-on neuron responded with similar discharges to all stimuli (Sl, S2, S3, S4, and R). The of stimuli. b: neuronal discharges in trials with an 0.5-s stimulus-on period and a 2.5-s started before onsets of stimuli. For each condition, 32 trials were accumulated. See

( 15%) showed larger changes in activity in response to S 1 than to the other sample stimuli. To confirm that the difference between the magnitudes of changes in activity was not due to the monkey’s eye fixation patterns, the monkey’s eye positions during the performance of this task were monitored. Fixation patterns did not depend on whether the stimulus was the first, second, third or fourth sample stimulus ( for example, see Fig. 3). Therefore, the difference between the magnitude of neuronal discharges in response to S1 and those in response to the other sample stimuli was not due to differences in the monkey’s eye fixation patterns. The data indicated that, in some selective visual neurons, the magnitude of changes in activity was modified by repetitive presentations of a stimulus. NONSELECTIVE VISUAL NEURONS. Thirteen neurons increased their discharge rates when a visual stimulus was presented, regardless of the nature of the stimulus and also regardless of the sample or the R. Latencies of these neurons ranged from 20 to 2 10 ms ( 124 t 52 ms, mean t SD) and were shorter than those of selective visual neurons (Mann-Whitney’s U test, P < 0.05). Response durations ranged from 30 to 620 ms ( 189 t 167 ms). There was no significant difference between response durations of these neurons and those of selective visual neurons. However, unlike selective visual neurons, none of these neurons showed relatively long response durations of >700 ms. When SI 1 and S12 values were calculated, they were zero in every case. Hence, these neurons were designated nonselective visual neurons. Figure 11 shows an example of the activity of a nonselective visual neuron. This neuron increased its firing rate when a visual stimulus was presented, and no clear effect of repetitive presentations of the same sample stimulus on the changes in activity of this neuron was detected (Fig. 11 A ). The remaining neurons showed similar patterns of changes in activity. In the case of 11 of 13 neurons, when the monkey failed to release the lever within 1.0 s of the onset of R, these neurons showed changes in activity, without presentation of a visual stimulus, after the end of a delay period that extended from the offset of R to the time at which the next stimulus would normally have been presented (Fig. 12A ) . We tested the neuron under conditions where R was not presented, i.e., only sample stimuli were presented. The neuron consistently changed its rate of discharges as if a subsequent visual stimulus had been presented (Fig. 12 B).

In the initial session, we tested this neuron under conditions where the duration of the stimulus-on period was 0.5 s and the duration of the delay period was 1.5 s ( Fig. 11 A ) . As illustrated in Fig. 11 A, the changes in activity started after the onset of the stimulus. When the delay period was longer, the changes in activity started sooner and the timing of the onset of the changes in activity became variable with respect to the onset of the visual stimulus. As illustrated in Fig. 11 B, the changes in activity of this neuron started before the onset of the stimulus in trials with a 2.5-s delay period. This property was detected in 5 of 13 nonselective visual neurons. Thus the temporal properties of these neurons, their latencies and response durations, changed depending on changes of the experimental conditions. Changes in activity during the delay period A total of 13 neurons showed changes in activity during the delay period. Of these, six selectively fired in response to particular visual stimuli during the stimulus-on period, and the firing continued throughout the subsequent delay period. These neurons were, therefore, selective visual neurons with selective activity during the delay period, and they were designated selective visual and delay neurons. The remaining seven neurons gradually increased their rates of discharge only during the delay period and did not have the stimulus-selective property; they were designated nonselective delay neurons.

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1s 12. Neuronal discharges of the same neuron as that used to generate Fig. 11. a: neuronal discharges of the neuron in a trial when the monkey failed to release the lever within 1.O s of the onset of R. b: neuronal discharges in a trial when no R was presented. Vertical bars: spike discharge from the neuron. Horizontal bars under headings: stimulus-on period. Horizontal dashed bars: anticipated stimulus. FIG.


VISUAL

RESPONSE PROPERTIES

Anexampleoffiring of a selective visual and delay neuron is illustrated in Fig. 13. The sustained firing was recorded from this neuron in response to a photograph of a human hand (Fig. 13A). As illustrated, the firing did not decline throughout the 3.0 s of the delay period. This neuron did not change its rate of discharges in response to a photograph of a syringe and during the delay period (Fig. 13B). This neuron showed changes in activity in response to four out of eight stimuli (SI 1 was 0.50), and only one out of the four stimuli elicited sustained firing during the delay period. The responses to the most effective stimulus (a photograph of a human hand) were greater than the responses to all other stimuli (S12 was 1.00, a discriminating neuron). The remaining five neurons also showed highly stimulus-selective properties (SIl values were 0.95, 0.92, 0.75, 0.75, and 0.48; S12 values were 1.00, 0.98, 1.00, 0.87, and 0.98, respectively). All but one of the selective visual and delay neurons were discriminating neurons ( YI = 3) or categorical neurons (n = 2)) and only one or two of the effective stimuli elicited sustained firing during the delay period. In five neurons, a total of six stimuli elicited sustained firing, namely, photographs of a Japanese monkey in an open field, a Japanese monkey in an open enclosure at our Institute, a chimpanzee, a man’s face unfamiliar to the monkey, an author’s face, and a human hand (see Fig. 13). The one remaining neuron showed sustained firing during the delay period in response to about one half of the tested stimuli, which ineluded human faces, monkeys, foods, and nonfood objects. NONSELECTIVE DELAY NEURONS. The rates of discharge from nonselective delay neurons gradually increased during the delay period and then decreased to the control level after the succeeding sample stimulus or R had been presented. An example of the changes in activity of a nonselecSELECTIVEVISUALANDDELAYNEURONS.

OF AMYGDALAR

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14. Activity of a nonselective delay neuron. A : neuronal responses illustrated as raster displays and the averaged peristimulus time histogram. Binwidth 20 ms. Discharge rates from this neuron gradually increased during delay periods. Thirteen trials were accumulated. Vertical lines: onsets of stimuli. Top: event chart illustrating stimulus-on and delay periods. See legend to Fig. 13 for details. B: activity of the same neuron when the monkey failed to release the lever within 1.O s of the onset of R. See legend to Fig. 12 for details. FIG.

tive delay neuron is illustrated in Fig. 14. As illustrated, the rate of discharges of this neuron changed, in particular during the latter half of the delay period, and a slight suppression was seen after the presentation of the succeeding stimulus (Fig. 14A ) . Five neurons ( 7 1% ) showed an increase in their discharge rates after the offset of the R when the monkey failed to release the lever within 1.O s of the onset of the R, just as nonselective visual neurons did (Fig. 14B). These nonselective delay neurons did not show increases in discharge rates during the waiting period. Therefore the increase occurred during the delay period rather than before presentation of a visual stimulus. Changes in activity during the reward period

FIG. 13. Stimulus-selective, sustained firing during the delay period of a selective visual and delay neuron, illustrated as raster displays and averaged peristimulus time histograms. A: neuronal discharges in trials in which the sample stimulus was a photograph ofa human hand. The firing contin ued during the entire delay period and did not decl ine. B : neuronal discharges in trials in which the sample stimulus was a photograph of a syringe. No change in activity was seen throughout the trials. Vertical lines: onsets of stimuli. Binwidth 50 ms. Eight trials were accumulated. Raster displays were sorted according to the number of sa.mple stimulus repetitions. Top: event chart illustrating stimulus-on and delay periods.

Nine neurons showed changes in activity during the reward period after an appropriate release of the lever. Seven of them also showed changes in activity in response to a drop of water administered independently of the task, and they were designated task-independent reward neurons; the remaining two neurons did not show such changes in activity and were designated task-dependent reward neurons. Figure 15, A and B, illustrates examples of the discharges of both types of neuron. The onsets of these neuronal discharges were time-locked more closely to the onset of the reward (Fig. 15, Ah and Bb) than to the onset of the R (Fig. 15, Aa and Ba). Under standard conditions, when the monkey performed the task correctly, a sound from personal computer B indicated his correct response. We also tested all these neurons under soundless conditions to study the effect of the sound on the neuronal responses, but the responses did not change. When a drop of water was administered independently of the task (when, of course, the monkey did not release the lever), the task-independent reward neuron also showed firing (Fig. 15Ac), whereas the task-dependent reward neuron did not (Fig. 15 Be). None of the reward neurons showed changes in activity when the monkey released the lever in error trials. Therefore it is unlikely that the changes in activity were related to monkey’s leverreleasing movements.


1458

K. NAKAMURA,

a *J Bk

A. MIKAMI,

AND K. KUBOTA

b

C

w

h

1.

I

1oosp / S

L 1s

FIG. 15. Changes in activity of 2 types of reward neuron, shown as perievent time histograms. A : responses of a task-independent reward neuron. Aa: neuronal discharges were aligned to the onset of the R. Ab: the same discharges were aligned to the delivery of the reward. AC: neuronal discharges of the same neuron when a liquid reward was administered independently of the task. B: responses of a task-dependent reward neuron. Thirty-two trials were accumulated. Binwidth 20 ms. Vertical bar under each histogram: onset of the event.

Distribution

of task-related neurons

One hundred thirty-four penetrations were made toward the lateral amygdala (mainly the lateral and the lateral basal nuclei), and task-related neuronal activity was recorded in 52 penetrations. We also made 56 penetrations medially (mainly toward the accessory basal nucleus), and task-related neurons were found in 15 penetrations. Although there was a sampling bias for the dorsolateral region, recordings from only 16 responsive neurons were obtained in the medial part of the amygdala, and many neurons were unresponsive. In this experiment, the medial region of the amygdala was apparently unresponsive. Figure 16 shows the locations of task-related neurons. Neurons that showed changes in activity during the stimulus-on period are illustrated in Fig. 16A, and locations of other task-related neu-

rons are shown in Fig. 16 B. One hundred twenty-one ( 92%) selective visual neurons (circles) were found in the lateral, the lateral basal and the central nuclei. Locations of selective visual neurons are summarized in Table 2. In the lateral nucleus, a relatively larger number of discriminating (filled circles) and categorical (circles with a dot) neurons (20 / 32) and a relatively smaller number of other selective visual neurons were found than in other nuclei (x2 test, x2 = 6.2 1, P < 0.05 ), and, in particular, more categorical neurons (x2 test, x2 = 7.00, P < 0.01) were found in the lateral nucleus. All neurons that selectively responded to particular stimuli with a certain significance were in the lateral nucleus; one was a categorical neuron at Al 8, one was a discriminating neuron at A 17, two were discriminating neurons, four were categorical neurons at A 16, and one

Al7 Al5 A14 Al6 16. Distribution of task-related neurons. A : locations of selective (circles) and nonselective ( * ) visual neurons. Filled circles, discriminating neurons; circles with a dot, categorical neurons; open circles, other selective visual neurons. Arrows: selective visual and delay neurons. B: locations of nonselective delay neurons ( A ), task-independent reward neurons ( w ), and task-dependent reward neurons ( EI) . Classification of nuclei in the amygdala is shown in A 18 in the bottom YOW (B). AB, the accessory basal nucleus; Ce, the central nucleus; Co, the cortical nucleus; Hip, the hippocampus; L, the lateral nucleus; LB, the lateral basal nucleus; LV, the lateral ventricle; MB, the medial basal nucleus; Me, the medial nucleus; OT, the optic tract; PAM, the periamygdaloid area. FIG.


VISUAL TABLE 2.

RESPONSE PROPERTIES

Nucleus of the Amygdala Type of Neuron

n

L

LB

Ce

MB

AB

Me

Discriminating Categorical Other selective visual Total

14 18 99 131

7 13*

3 2 35s 40

2 3 19 24

2 0 2 4

0 0 4 4

0 0 2 2

57

L, lateral nucleus; LB, lateral basal nucleus; Ce, central nucleus; MB, medial basal nucleus; AB, accessory basal nucleus; Me, medial nucleus. *The ratio of the number of the given type of neuron to the number of task-related neurons was significantly high (x2 test, P < 0.0 1). tThe ratio was significantly low (x2 test, P < 0.05). *The ratio was significantly high (x2test, P < 0.05).

was a categorical neuron at A 14. By contrast, in the lateral basal nucleus, the relative proportion of these two types of neuron was lower and that of other selective visual neurons was higher than in other nuclei (x 2 test, x2 = 4.44, P < 0.05). Each selective visual and delay neuron is indicated by an arrow. They were located in the relatively anterior part of the amygdala. Six of 13 nonselective delay neurons ( A ) and five of seven nonselective visual neurons ( * ) were located in the lateral basal nucleus. Eight of nine reward neurons were located in the posterior part of the amygdala (A 14- 16 ) . The distributions of all types of task-related neuron among the nuclei of the amygdala are summarized in Table 3. As shown in the table, 90% of the task-related neurons were located in the lateral ( y1 = 63 ) , the lateral basal (~2 = 55) and the central (~2 = 26) nuclei. Hence, to study the difference in the distribution of task-related neurons among the nuclei, the ratio of the number of each type of neuron to the number of the other types of task-related neurons was examined for three nuclei, namely, the lateral, the lateral basal, and the central nuclei. In the lateral nucleus, selective visual neurons were dominant (x 2 test, x 2 = 5.18, P < 0.05 ). By contrast, in the lateral basal nucleus, the proportion of selective visual neurons was low (x2 test, x 2 = 4.73, P < 0.05) and the proportion of nonselective delay neurons was high (x2 test, x2 = 4.46, P < 0.05). TABLE

NEURONS

1459

DISCUSSION

Locationsof selectivevisual neurons

37t

OF AMYGDALAR

In the present study, various patterns of changes in activity were recorded during the performance of a visual discrimination task. Most of the task-related neurons showed changes in activity during the stimulus-on period in response to various visual stimuli, and some of them showed changes in activity during the delay period and during the reward period. Quantijication

of stimulus selectivity

Many task-related amygdalar neurons showed different magnitudes of responses to different stimuli. To evaluate the differential properties of the responses, two selectivity indexes were employed in this experiment. One (SI 1) was employed to evaluate the proportion of all tested stimuli that elicited responses from a neuron. In this respect, visually responsive neurons showed various values of SIl, that is, some amygdalar neurons responded to almost all visual stimuli, but some other neurons responded only to a few stimuli. However, this index was unsatisfactory for evaluating the ability of a neuron to discriminate one stimulus from another. As a measure of this ability, the second index (SI2), based on relative magnitude of responses to different stimuli, was employed. Some visually responsive amygdalar neurons had very high values of S12, that is, these neurons responded more to a few stimuli than to the other stimuli. By contrast, other neurons had very low values, that is, these neurons showed similar responses to all stimuli. The natures of the various effective stimuli were studied for each neuron. Most of the neurons with high values of S12 tended to respond to stimuli that had a behavioral significance outside the task, such as a human face, a monkey, food, and a nonfood object. Therefore, as a consequence, S12 was more useful and meaningful than SIl for evaluation of the differential properties of the responses of amygdalar neurons. In this study, the neuron was regarded as nonselective if both SI 1 and S12 values were equal to zero. If either the SI 1 value or the S12 value was not equal to zero, the neuron responded, to a greater or lesser extent, differentially to different stimuli and was regarded as selective.

3. Summary of task-relatedneuronsin the amygdala Nucleus of the Amygdala Type of Neuron

Visual Selective visual Nonselective visual Delay Selective visual and delay* Nonselective delay Reward Task-independent reward Task-dependent reward Total

n

L

LB

Ce

MB

AB

Me

131 13

57* 4

40-t 6

24 1

4 0

4 0

2 2

6 7

2 0

2 5*

1 0

1 0

0 1

0 1

7 2 160

1 1 63

0 1 26

0 0 4

2 0 7

0 0 5

4 0 55

On the basis of the values of SI 1 and S12, neurons were classified as selective and nonselective. L, lateral nucleus; LB, lateral basal nucleus; Ce, central nucleus; MB, medial basal nucleus; AB, accessory basal nucleus; Me, medial nucleus. *The ratio of the number of the given type of neuron to the number of task-related neurons was significantly high (x2 test, P< 0.05). tThe ratio was significantly low (x2 test, P < 0.05). $A11selective visual and delay neurons belonged to the class of selective visual neurons. Recordings from fewer than 10 task-related neurons were obtained from the MB, the AB, and the Me. Therefore the statistical method was used to analyze data from the neurons in the L, the LB, and the Ce.


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Selective visual neurons One fourth of selective visual neurons were regarded as discriminating or categorical neurons. The responses of these neurons apparently reflected to some categorical aspects of the stimuli, such as a human, a monkey, food, or a nonfood object. It is of interest that the most effective stimuli of about one half of the neurons were images of monkeys. We also used two-dimensional colored shapes as visual stimuli during recordings from some neurons, but none of them gave maximal responses to such two-dimensional shapes. These data suggest that some behavioral significance of the stimulus may be important for the amygdalar neurons. Some neurons responded only to particular stimuli with a certain behavioral significance outside the task, such as a particular person, smiling human faces, threatening monkey faces, food pellets, etc. Stimulus-selective visual neurons have been reported in the inferotemporal cortex and the superior temporal sulcus (Baylis et al. 1985; Bruce et al. 1981; Desimone et al. 1984; Gross et al. 1972; Mikami and Nakamura 1988; Perret et al. 1982; Sato et al. 1980; Schwartz et al. 1983). In the cited studies, there are many reports of visual neurons that were selective for complex stimuli, such as a face or a hand. The majority of face-selective neurons in the inferotemporal cortex and the superior temporal sulcus showed changes in activity in response to both human and monkey faces, and the changes in activity of these neurons were sensitive to the orientation of the head or to parts of faces. By contrast, in the present study, amygdalar neurons showed changes in activity in response to a variety of views of the face of a particular individual, almost regardless of the orientation of the face and the facial expression. It is unlikely that these neurons were selective for some simple feature of the stimulus, such as a color, a region of brightness, a texture, or a shape. Because the effective stimuli differed from neuron to neuron, it is also unlikely that the differential responses were related only to more the general state of the animals, such as their attention or arousal level. Therefore these neurons seemed to be involved in the recognition or evaluation of the behavioral significance of complex stimuli. This hypothesis is consistent with the notion that the amygdala is involved in stimulus evaluation ( LeDoux 1987 ) . Selective visual neurons were located mainly in the dorsolateral part of the amygdala, especially in the dorsal part of the lateral and the lateral basal nuclei. This result is consistent with results from other single-neuron recording studies (Nishijo et al. 1988a,b; Sanghera et al. 1979). The medial half of the amygdala was apparently unresponsive in this experiment, perhaps because only two-dimensional stimuli, namely colored photographs, were used as visual stimuli and, as in other experiments (Nishijo et al. 1988a,b), real three-dimensional stimuli. Anatomically, the dorsal part of the lateral and lateral basal nuclei receives projections from the inferotemporal cortex and the superior temporal sulcus (Aggleton et al. 1980; Herzog and Van Hoesen 1976; Iwai and Yukie 1987; Iwai et al. 1987; Jones and Powell 1970; Turner et al. 1980), regions that are thought to be involved in higher visual processing. Fukuda et al. ( 1987) reported that cooling of the inferotemporal cortex modulated changes in activity of amygdalar neurons in re-

AND K. KUBOTA

sponse to visual stimuli. Selective visual neurons may receive visual input from the inferotemporal cortex. In 15% of selective visual neurons, the magnitude of discharges in response to Sl was larger than the magnitudes of discharges in response to the second, third and fourth sample stimuli. Nishijo et al. ( 1988a,b) reported that amygdalar neurons changed their rates of discharges on the basis of whether or not the stimulus was novel (or familiar) to the monkey. Therefore it is possible that the difference in the magnitudes of discharges between the response to Sl and responses to the other sample stimuli might be due to the novelty (or familiarity) of the stimulus. However, the visual stimuli used in this experiment were presented repeatedly to the monkey during training and recording sessions, and, therefore, none of the visual stimuli were new to the monkey. Furthermore, not only Sl but also R were novel within trials. However, in the case of these neurons, the magnitudes of changes in activity in response to R were not larger than those to the second, third or fourth sample stimuli. One explanation for this result is that a difference in the monkey’s level of attention may bring about the difference in the magnitudes of discharges, that is, during recording sessions for these neurons, the monkey might be more attentive to Sl than to the other visual stimuli, and the monkey’s level of attention could modulate the magnitude of discharges. Selective visual and delay neurons A small portion of neurons showed sustained firing in response to particul .ar sample sti muli while the monkey was memorizing the stimuli. Therefore the sustained firing during the delay period might be related to short-term storage of information of complex visual stimuli. In our task situation, it is also difficult to rule out the possibility that the sustained firing was due to attention or anticipation. However, the firing was highly stimulus-dependent and depended not on R but on the sample stimuli. Therefore, we consider that the possibility is unlikely. The relatively low ratio of the number of these neurons to that of selective visual neurons ( 5%) corresponds to the observation that the sustained firing was highly stimulus selective. It is probable that some of the remaining neurons showed sustained firing in response to stimuli that we failed to test. Stimulus-selective, sustained firing during the delay period of memory tasks has been recorded from various structures related to memory function, such as the prefrontal cortex (Funahashi et al. 1989; Fuster 1973; Kojima and Goldman-Rakic 1982; Kubota and Niki 197 1; Niki 1974)) the cingulate cortex (Niki and Watanabe 1976), the dorsomedial thalamus (Fuster and Alexander 1973 ), the ventral part of the inferotemporal cortex ( Miyashita and Chan 1988 ) , and the superior temporal sulcus (Fuster and Jervey 1982; Mikami 1987) of monkeys, and the firing is considered to represent the short-term storage of sensory information. We also found the sustained firing of single neurons in the anteroventral tip of the inferotemporal cortex (the temporal pole) of monkeys under the same task condition (Nakamura et al. 199 1, 1992). The ratio of the number of neurons that exhibited the sustained firing during the delay period to the number of selective visual neurons in the temporal pole


VISUAL

RESPONSE PROPERTIES

(2 l/92) was significantly higher than that in the amygdala (6/131; x2 test, x2 = 16.9, P < 0.01). The present data suggest that the monkey amygdala is involved in the shortterm storage of visual information to some extent, but the contribution of the amygdala to short-term memory seems relatively small based on the smaller percentage of the neurons exhibiting the sustained firing during the delay period. Zola-Morgan et al. ( 1989) recently reported that lesions of the amygdala alone, which spared the adjacent cortex, did not impair performance of a delayed nonmatching-tosample task, suggesting that the monkey amygdala does not contribute to short-term storage of complex visual stimuli. The difference between their results and ours may be due to the fact that several of the experimental conditions were different between the two studies, for example, the visual stimuli used ( 3-dimensional in their experiment as distinct from 2-dimensional in our experiment), presentation of the stimulus (trial-unique in their experiment and repetitive in our experiment), and pretraining in performance of the behavioral task (no training in their experiment and training in our experiment). In addition, our present data indicate that the amygdala could contribute to the recognition for specific types of stimuli, such as faces and food. These stimuli were not employed by Zola-Morgan et al. Probably our results are likely consistent with the data of Zola-Morgan et al., that is, the results of lesion studies were probably due to the relatively small contribution of the amygdala to short-term memory. Nonselective neurons Nonselective visual neurons showed changes in activity when a visual stimulus was presented, regardless of the nature of the stimulus and regardless of sample stimulus or R. Latencies of these neurons were shorter than those of selective visual neurons. Furthermore, these neurons showed changes in activity in the absence of a visual stimulus when the monkey failed to release the lever in response to R, probably because he was unable to discriminate R from the sample stimulus, and, therefore, he was waiting for the arrival of the next stimulus. These changes were not considered to be involved in the direct analysis of visual stimuli, but they might be related to the anticipation of visual stimuli and/or to the monkey’s level of attention or arousal. Nonselective delay neurons gradually increased their discharge rates during the delay period, regardless of the stimuli, and the rates of discharges decreased to the control level after the next stimulus was presented. When the monkey failed to respond to R, these neurons, like nonselective visual neurons, showed changes in activity after the offset of R. These neurons might also be related to the anticipation of visual stimuli and/or to the monkey’s level of attention. In this task, for correct performances, it was necessary for the monkey to release the lever within 1.O s of the onset of R. The monkey may have anticipated the appearance of a visual stimulus beforehand and changed his level of attention. Anatomically, the amygdala receives projections from the nonspecific nuclei of the thalamus (Aggleton et al. 1980) and the locus coeruleus (Mehler 1980; Norita and Kawamura 1980), which are considered to be related to attention or arousal, and projections terminate more fre-

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quently in the lateral basal nucleus than in the lateral nucleus. Nonselective neurons were more numerous in the lateral basal nucleus than in the lateral nucleus. The data suggest that nonselective neurons may receive afferent projections from the nonspecific nuclei of the thalamus and/ or the locus coeruleus and might be related to the attention. Reward neurons Some neurons responded when the monkey was rewarded. Task-independent reward neurons responded when a drop of water was administered independently of the task. In the present study, the delivery of a reward was accompanied by a small sound of a solenoid, which was masked by sounds of spikes during recordings. It is unlikely that these neurons responded to the sound of the solenoid. Probably, the responses of the neurons were related to oral sensation and/ or movements or to gustatory stimuli. These data are consistent with results of previous recording studies (Nakano et al. 1987; Nishijo et al. 1988a,b) and with those of an anatomic study (Turner et al. 1980). However, task-dependent reward neurons responded only when the monkey was rewarded after his correct responses. It could be said that the responses of these neurons were related to the monkey’s correct responses. Roles of the monkey amygdala The present study demonstrates that amygdalar neurons in the monkey show various patterns of changes in activity during the performance of the visual discrimination task. Selective visual neurons located in the dorsolateral part of the amygdala, probably receiving visual information from the inferotemporal cortex, may be involved in recognition of complex visual stimuli or in the evaluation of certain behavioral significance of the stimuli outside the task. Selective visual and delay neurons may store the information temporarily, but the contribution of the amygdala to shortterm storage of sensory information may be small. Probably, a small portion of amygdalar neurons store visual information temporarily, and they will be capable of contributing to the short-term memory function cooperatively with other structures, such as the inferotemporal cortex and the hippocampus. In addition, nonselective visual neurons located relatively medially in the amygdala, receiving inputs from the nonspecific nuclei of the thalamus, may provide background activities for visual processing, such as anticipation of visual stimuli or direction of attention to visual stimuli. Nonselective delay neurons may contribute to sustain the monkey’s level of attention, supporting other functions such as memory function. Lastly, some of the neurons, located relatively more frequently in the posterior part of the amygdala, showed changes in activity in response to the reward or to the receipt of water. All these data together show that the monkey’s amygdala is actively involved in the visual recognition and/ or evaluation of complex stimuli, leading to the production of an appropriate emotional or social behavior by sending the information to the hypothalamus.


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A. MIKAMI,

The authors thank T. Miwa for technical assistance. The authors are also grateful to Dr. Takao Oishi for valuable suggestions on statistical treatments. This work was partly supported by Grants-in-Aid for Scientific Research (No. 01570063, in 1989 and 1990, and No. 02255212, in 1990) from the Ministry of Education, Science and Culture, Japan. This work was also supported by funds provided by Nippon Telegraph and Telephone Corporation (NTT) Human Interface Laboratories as part of a research agreement between Kyoto University and NTT. Address for reprint requests: K. Kubota, Dept. of Neurophysiology, Primate Research Institute, Kyoto University, Inuyama, Aichi 484, Japan. Received 22 April 199 1; accepted in final form 16 January 1992. REFERENCES J. P., BURTON, M. J., AND PASSINGHAM, R. E. Cortical and subcortical afferents to the amygdala of the rhesus monkey (Macaca mulatta). Brain Res. 190: 347-368, 1980. AGGLETON, J. P. AND PASSINGHAM, R. E. Syndrome produced by lesions of the amygdala in monkeys (Macaca mulatta). J. Comp. Physiol. Psychol. 95: 96 I-977, 198 1. AGGLETON, J. P. AND PASSINGHAM, R. E. Stereotaxic surgery under x-ray guidance in the rhesus monkey, with special reference to the amygdala. Exp. Brain Res. 44: 27 I-276, 198 1. AMARAL, D. G. AND PRICE, J. L. Amygdalo-cortical projections in the monkey (Macaca fascicularis). J. Comp. Neurol. 230: 465-496, 1984. ANDERSEN, R. Cognitive changes after amygdalotomy. Neuropsychologia 16: 439-451, 1978. BAYLIS, G. C., ROLLS, E. T., AND LEONARD, C. M. Selectivity between faces in the responses of a population of neurons in the cortex in the superior temporal sulcus of the monkey. Brain Res. 342: 9 I- 102, 1985. BRUCE, C., DESIMONE, R., AND GROSS, C. G. Visual properties of neurons in a polysensory area in superior temporal sulcus of the macaque. J. Neurophysiol. 46: 369-384, 198 1. CROSBY, E. C. AND HUMPHREY, T. Studies of the vertebrate telencephalon. II. The nuclear pattern of the anterior olfactory nucleus, tuberculum olfactrium and the amygdaloid complex in adult man. J. Comp. Neurol. 74: 309-352, 194 1. DESIMONE, R., ALBRIGHT, T. D., GROSS, C. G., AND BRUCE, C. Stimulusselective properties of inferior temporal neurons in the macaque. J. Neurosci. 4: 205 l-2062, 1984. DICKS, D., MYERS, R. E., AND KLING, A. Uncus and amygdala lesions: effects on social behavior in the free-ranging rhesus monkey. Science Wash. DC 165: 69-7 1, 1969. FUKUDA, M., ONO, T., AND NAKAMURA, K. Functional relations among inferotemporal cortex, amygdala, and lateral hypothalamus in monkey operant feeding behavior. J. Neurophysiol. 57: 1060-1077, 1987. FUNAHASHI, S., BRUCE, C. J., AND GOLDMAN-RAKE, P. S. Mnemonic coding of visual space in the monkey’s dorsolateral prefrontal cortex. J. Neurophysiol. 6 1: 33 l-349, 1989. FUSTER, J. M. Unit activity in prefrontal cortex during delayed-response performance: neuronal correlates of transient memory. J. Neurophysiol. 36: 61-78, 1973. FUSTER, J. M. AND ALEXANDER, G. E. Firing changes in cells of the nucleus medialis dorsalis associated with delayed response behavior. Brain Res. 61: 79-91, 1973. FUSTER, J. M. AND JERVEY, J. P. Neuronal firing in the inferotemporal cortex of the monkey in a visual memory task. J. Neurosci. 2: 36 l-375, 1982. FUSTER, J. M. AND UYEDA, A. A. Reactivity of limbic neurons of the monkey to appetitive and aversive signals. Electroencephalogr. Clin. Neurophysiol. 30: 28 I-293, 197 1. GESCHWIND, N. Disconnexion syndromes in animals and man. Brain 88: 237-294. 1965. GLOOR, P., OLIVER, A., AND QUESNEY, L. F. The role of the amygdala in the expression of psychic phenomena in temporal lobe seizures. In: The Amygdaloid Complex, edited by Y. Ben-Ari. Amsterdam: Elsevier, 198 1, p. 409-420. GODDARD, G. V. Functions of the amygdala. Psychol. Bull. 62: 89- 109, 1964. GROSS, C. G., ROCHA-MIRANDA, C. E., AND BENDER, D. B. Visual properties of neurons in inferotemporal cortex of the macaque. J. Neurophysiol. 35: 96-111, 1972. AGGLETON,

AND K. KUBOTA

A. G. AND VAN HOESEN, G. W. Temporal neocortical afferent connections to the amygdala in the rhesus monkey. Brain Res. 115: 57-69, 1976. HOREL, J. A., KEATING, E. G., AND MISANTONE, L. J. Partial Kluver-Bucy syndrome produced by destroying temporal neocortex or amygdala. Brain Res. 94: 347-359, 1975. IWAI, E. AND YUKIE, M. Amygdalofugal and amygdalopetal connections with modality-specific visual cortical areas in macaques (Macaca fuscata, A4. mulatta, A4. fascicularis). J. Comp. Neural. 26 1: 362-387, 1987. IWAI, E., YUKIE, M., SUYAMA, H., AND SHIRAKAWA, S. Amygdalar connections with middle and inferior temporal gyri of the monkey. Neurosci. Lett. 83: 25-29, 1987. JONES, E. G. AND POWELL, T. P. S. An anatomical study of converging sensory pathways within the cerebral cortex of the monkey. Brain 93: 793-820, 1970. JUDGE, S. J., RICHMOND, B. J., AND CHU, F. C. Implantation of magnetic search coils for measurement of eye position: an improved method. Vision Res. 20: 535-538, 1980. KLING, A. AND STEIUIS, H. D. A neural substrate for affiliative behavior in nonhuman primates. Brain Behav. Evol. 13: 2 16-238, 1976. KOJIMA, S. AND GOLDMAN-RAIUC, P. S. Delay-related activity of prefrontal neurons in rhesus monkeys performing delayed response. Brain Res. 248: 43-49, 1982. KUBOTA, K. AND NW, H. Prefrontal cortical unit activity and delayed alternation performance in monkeys. J. Neurophysiol. 3: 337-347, 1971. LEDOUX, J. E. Emotion. In: Handbook of Physiology. The Nervous System. Higher Functions ofthe Brain. Washington, DC: Am. Physiol. Sot., 1987, sect. 1, vol. V, chapt. 10, p. 4 19-460. LEONARD, C. M., ROLLS, E. T., WILSON, F. A. W., AND BAYLIS, G. C. Neurons in the amygdala of the monkey with responses selective for faces. Behav. Brain Res. 15: 159-176, 1985. MACLEAN, P. D. Psychosomatic disease and the “visceral brain.” Recent developments bearing on the Papez theory of emotion. Psychosom. Med. 11: 338-353, 1949. MACLEAN, P. D. Some psychiatric implications of physiological studies on frontotemporal portion of limbic system (visceral brain). Electroencephalogr. Clin. Neurophysiol. 4: 407-4 18, 1952. MEHLER, W. Subcortical afferent connections of the amygdala in the monkey. J. Comp. Neurol. 190: 733-762, 1980. MIKAMI, A. Neuron activities in the macaque superior temporal sulcus during the sequential discrimination of faces(Abstract). J. Physiol. Sot. Jpn. S49, 1987. MIKAMI, A. AND NAKAMURA, K. Behavioral role of stimulus selective neuronal activities in the superior temporal sulcus of macaque monkeys. Sot. Neurosci. Abstr. 14: 10, 1988. MISHKIN, M. Memory in monkeys severely impaired by combined but not by separate removal of amygdala and hippocampus. Nature Lond. 273: 297-298, 1978. MISHKIN, M. A memory system in the monkey. Philos. Trans. R. Sot. Land. B Biol. Sci. 298: 85-95, 1982. MIYASHITA, Y. AND CHAN, H. S. Neuronal correlate of pictorial shortterm memory in the primate temporal cortex. Nature Lond. 33 1: 68-70, 1988. MURRAY, E. A. Representational memory in nonhuman primates. In: Neurobiology of Comparative Cognition, edited by R. P. Kenser and D. S. Olton. Hillsdale, NJ: Erlbaum, 1990, p. 127- 155. MURRAY, E. A. AND MISHKIN, M. Visual recognition in monkeys following rhinal cortical ablations combined with either amygdalectomy or hippocampectomy. J. Neurosci. 6: 199 l-2003, 1986. NAKAMURA, K., MIKAMI, A., AND KUBOTA, K. Neuronal activities in the amygdala of rhesus monkey during a sequential visual discrimination task with delay (Abstract). Neurosci. Res. 9, Suppl.: S79, 1989a. NAKAMURA, K., MIKAMI, A., AND KUBOTA, K. Stimulus selective neuronal responses to colored photographs in the amygdala of the rhesus monkey (Abstract). Jpn. J. Physiol. 39, Suppl.: S 166, 1989b. NAKAMURA, K., MIKAMI, A., AND KUBOTA, K. Stimulus selectivity correlated with temporal characteristics in amygdala visual neurons of the rhesus monkey (Abstract). Jpn. J. Physiol. 40, Suppl.: S 184, 1990. NAKAMURA, K., MIKAMI, A., AND KUBOTA, K. Oscillatory activity related to short-term memory in the temporal pole of monkeys. Sot. Neurosci. Abstr. 17: 660, 199 1. HERZOG,


VISUAL

RESPONSE PROPERTIES

NAKAMURA,K.,MIKAMI, A., ANDKUBOTA, KOscillatoryneuronalactivity related to visual short-term memory in monkey temporal pole. Neuroreport 3: 117-120, 1992. NAKANO, Y., LENARD, L., OOMURA, Y., NISHINO, H., Aou, S., AND YAMAMOTO, T. Functional involvement of catecholamines in reward-related neuronal activity of the monkey amygdala. J. Neurophysiol. 57: 72-91, 1987. NIKI, H. Differential activity of prefrontal units during right and left delayed response trials. Brain Res. 70: 346-349, 1974. NW, H. AND WATANABE, M. Cingulate unit activity and delayed response. Brain Res. 110: 381-386, 1976. NISHIJO, H., ONO, T., AND NISHINO, H. Topographic distribution of modality-specific amygdalar neurons in alert monkey. J. Neurosci. 8: 3556-3569, 1988a. NISHIJO, H., ONO, T., AND NISHINO, H. Single neuron responses in amygdala of alert monkey during complex sensory stimulation with affective significance. J. Neurosci. 8: 3570-3583, 1988b. NORITA, M. AND KAWAMURA, K. Subcortical afferents to the monkey amygdala: an HRP study. Brain Res. 190: 225-230, 1980. ONO, T., FUKUDA, M., NISHINO, H., SASAKI, K., AND MURAMOTO, K. Amygdaloid neuronal responses to complex visual stimuli in an operant feeding situation in the monkey. Brain Res. Bull. 11: 5 15-5 18, 1983. PERRET, D. I., ROLLS, E. T., AND CAAN, W. Visual neurones responsive to faces in the monkey temporal cortex. Exp. Brain Res. 47: 329-342, 1982. PRICE, J. L. Toward a consistent terminology for the amygdaloid complex. In: The Amygdaloid Complex, edited by Y. Ben-Ari. Amsterdam: Elsevier, 1981, p. 13-18. ROLLS, E. T. Neurons in the cortex of the temporal lobe and in the amygdala of the monkey with responses selective for faces. Hum. Neuro~ioZ. 3: 209-222, 1984. ROSVOLD, H. E., MIRSKY, A. F., AND PRIBRAM, K. H. Influence of amygdalectomy on social behavior in monkeys. J. Camp. Physiol. Psychol. 47: 173-178, 1954.

OF AMYGDALAR

NEURONS

1463

M. K., ROLLS, E. T., AND ROPER-HALL, A. Visual responses of neurons in the dorsolateral amygdala of the alert monkey. Exp. Neural. 63: 610-626, 1979. SARTER, M. AND MARKOWITSCH, H. J. Involvement of the amygdala in learning and memory: a critical review, with emphasis on anatomical relations. Behav. Neurosci. 99: 342-380, 1985. SATO, T., KAWAMURA, T., AND IWAI, E. Responsiveness of inferotemporal single units to visual pattern stimuli in monkeys performing discrimination. Exp. Brain Res. 38: 3 13-3 19, 1980. SAUNDERS, R. C., MURRAY, E. A., AND MISHKIN, M. Further evidence that amygdala and hippocampus contribute equally to recognition memory. Neuropsychologia 22: 785-796, 1984. SCHWARTZ, E. L., DESIMONE, R., ALBRIGHT, T. D., AND GROSS, C. G. Shape recognition and inferior temporal neurons. Proc. NatZ. Acad. Sci. USA 80: 5776-5778, 1983. SUZUKI, H. AND AZUMA, M. A method for the accurate localization of recording sites in chronic monkey experiments. In: Integrative Control Function of the Brain, edited by M. Ito et al. Amsterdam: Elsevier, 1979, vol. 2, p. 405-407. THOMPSON, C. I., BERGLUND, R. M., AND TOWFIGHI, J. T. Social and nonsocial behaviors of adult rhesus monkeys after amygdalectomy in infancy or adulthood. J. Comp. Physiol. Psychol. 9 1: 533-548, 1977. TURNER, B. H., MISHKIN, M., AND KNAPP, M. Organization ofthe amygdalopetal projections from modality-specific cortical association areas in the monkey. J. Comp. NeuroZ. 19 1: 5 15-543, 1980. WEISKRANTZ, L. Behavioral changes associated with ablations of the amygdaloid complex in monkeys. J. Comp. Physiol. Psychol. 49: 38 l391, 1956. WURTZ, R. H. Response of striate cortex neurons to stimuli during rapid eye movements in the monkey. J. NeurophysioZ. 32: 975-986, 1969. ZOLA-MORGAN, S., SQUIRE, L. R., AND AMARAL, D. G. Lesions of the amygdala that spare adjacent cortical regions do not impair memory or exacerbate the impairment following lesions of the hippocampal formation J. Neurosci. 9: 1922-1936, 1989. SANGHERA,


Visual responses of neurons in the dorsolateral amygdala of the alert monkey.

Neuronal activity in visual, auditory and polysensory areas in the monkey temporal cortex during visual fixation task.

Effects of LSD-25 on performance of a visual discrimination task in brain-damaged rats.

Effects of spatial congruency on saccade and visual discrimination performance in a dual-task paradigm.

Responses of monkey midbrain dopamine neurons during delayed alternation performance.

Neurons in the monkey amygdala detect eye contact during naturalistic social interactions.

Visual discrimination in the monkey: distinguishing the incorrect response.

Activity of human hippocampal formation and amygdala neurons during sleep.

Visual discrimination in monkey with removal of inferotemporal cortex.

Monkey Prefrontal Neurons Reflect Logical Operations for Cognitive Control in a Variant of the AX Continuous Performance Task (AX-CPT).

Dynamic information flow analysis in Vascular Dementia patients during the performance of a visual oddball task.

Activity of neurons in the region of the substantia nigra during feeding in the monkey.

Residual sensory capacities of the deaf: a signal detection analysis of a visual discrimination task.

A pencil rescues impaired performance on a visual discrimination task in patients with medial temporal lobe lesions.

Activity of identified wrist-related pallidal neurons during step and ramp wrist movements in the monkey.

Stimulus similarity determines the prevalence of behavioral laterality in a visual discrimination task for mice.

Single unit activity in the lateral amygdala of the cat during sleep and waking.

Involvement of the human medial temporal lobe in a visual discrimination task.

Maintained activity of single neurons in the cat visual cortex at different levels of retinal adaptation.

Cortical configuration by stimulus onset visual evoked potentials (SO-VEPs) predicts performance on a motion direction discrimination task.

Attentional Mechanisms during the Performance of a Subsecond Timing Task.

Changes in activity of fast-spiking interneurons of the monkey striatum during reaching at a visual target.

Basal forebrain dynamics during a tactile discrimination task.

Movement-Related Activity of Human Subthalamic Neurons during a Reach-to-Grasp Task.