Topographic studies on visual neurons in the dorsolateral prefrontal cortex of the monkey
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Exp Brain Res (1983) 53:47-58 E . _mental Brain Research 9 Springer-Verlag 1983
Topographic Studies on Visual Neurons in the Dorsolateral Prefrontal Cortex of the Monkey*
H. Suzuki and M. Azuma
Dept. of Physiology, Hirosaki University Faculty of Medicine, Hirosaki 036, Japan
Summary. The topographic distribution and organi- zation of visual neurons in the prefrontal cortex was examined in alert monkeys. The animal was trained to fixate straight ahead onto a tinty, dim light spot. While he was fixating, we presented a stationary second light spot (RF spot) at various locations in the visual field and examined unit responses of the prefrontal neurons to the RF-spot stimulus. Many prefrontal neurons, especially those located in the relatively superficial layers of the cortex, responded with a phasic and/or tonic activation to the RF spot illuminating a limited extent of the visual field, a receptive field (RF) being so determined. The visual neurons were found to be widely distributed in the prearcuate and inferior dorsolateral areas. One hemisphere mainly represented the contralateral vis- ual field. According to the location of the neurons in these areas, their visual properties varied with re- spect to RF eccentricity from the fovea and in size. The neurons located in the lateral part of the areas and close to the inferior arcuate sulcus had relatively small RFs representing the foveal and parafoveal regions. When the recording site was moved medially, the RFs became eccentric from the fovea and were larger. Then, the neurons located between the caudal end of the principal sulcus and the arcuate sulcus had RFs with a considerable eccentricity. The size of the RF became progressively larger for anteriorly located neurons and this occurred gener- ally without a change in RF eccentricity. The visual neurons were not organized on a regular pattern in the cortex with regard to their RF direction (vector angle) from the foveal region. From these observa- tions, we conclude, first, that the prearcuate and inferior dorsolateral areas of the prefrontal cortex
* Supported by Grant-in-aid for Scientific Research 444022, 587030 and Special Project Research Grant 56121-- [ from the Ministry of Education, Science and Culture of Japan
Offprint requests to: Hisao Suzuki, MD (address see above)
are functionally differentiated so that the lateral area's function is related to central vision, while that of the medial area to ambient vision. Second, the RF representation on the cortex with loss of the vector relation may generate an interaction between sepa- rate objects in visual space and may subserve the control of attention ]performance.
Key words: Visual neuron - Prefrontal cortex - Alert monkey - Visual representation - Visual receptive field
In a previous paper', we showed that the inferior dorsolateral and inferior prearcuate areas (IDL) of the prefrontal cortex contain many neurons which increase their discharge rate during foveal fixation on a light spot (Suzuki and Azuma 1977). Further investigation revealed that the activation includes several visual processes including an intentional one (Suzuki et al. 1979). These cortical regions may mediate functions concerned with central vision such as visual foveation to an object or visual attention in a broad sense. On the other hand, the prearcuate area posterior to the end of the principal sulcus seems to mediate processes relating to ambient vision. Using alert monkeys, Mohler et al. (1973) found neurons in the area that had a relatively large receptive field (RF) often located in the peripheral visual field contralateral to the recording hemi- sphere. The neurons did not show activation during fixation to a visual stimulus per se, indicating that they had rather peripheral RFs, sparing the fovea. These neurons frequently showed an enhancement of their visual response when the animal made a saccade to a stimulus in the RF (Wurtz and Mohler 1976;
48 H. Suzuki and M. Azuma: Topography of Prefrontal Neurons
Goldberg and Bushnell 1981). Such a functional differentiation within the prefrontal cortex in terms of neuronal location was also described by Pigarev et al. (1979). Neurons anteriorly located in the ar- cuate region required more complex visual stimuli for their activation as compared to posteriorly located neurons.
Thus, it is expected that a wide area of the prefrontal cortex is concerned with the processing of visual information, and may further be differentiated with respect to specific visual functions. Recently, Mikami et al. (1982) found visual neurons over a wide area of prefrontal cortex, but they did not mention the areal differences of their neuronal properties. In this paper, we report the investigation of a neuron population widely located in the periprin- cipal and periarcuate areas of the prefrontal cortex in order to elucidate their different visual properties with particular reference to properties of visual RF. A preliminary report has appeared elsewhere (Azuma and Suzuki 1981).
Training of Fixation Behavior
Six male monkeys (Macaca rnulatta) weighing 5.0-8.4 kg were used. The monkeys were first trained to gaze steadily at a tiny, dim light spot (Wurtz 1969; Suzuki and Azuma 1977; Suzuki et al. 1979; Mikami et al. 1982). Each animal was seated in a primate chair facing a translucent screen 1.5 x 1.5 m square, illuminated diffusely at 1 cd/m 2 and placed 58 cm away from his eyes. After an intertrial interval of 4--6 s, a tiny, faint spot appeared on the center of the screen. By pressing a lever in front of him, the center spot stayed on for a duration of multiples of 0.5 s from 1 to 4 s, and then it slightly brightened for 0.5 s. A rapid lever-release within this bright period (except for the first 0.2 s) resulted in the delivery of 0.1-0.2 ml of orange-flavored sweet juice with the turning off of the light spot. The light spot was as small as 0.1 ~ in visual angle and the level of brightening was near-threshold for detection. There- fore, the monkey could not detect the brightening unless he gazed directly at the spot. Thus, a continuous gaze behavior was elicited during the light-spot presentation.
The training method for this fixation task was described in detail in other papers (Suzuki and Azuma 1977; Suzuki et al. 1979). In this training for fixation, it was essential that very early in the training period the animal was taught to select the center spot as the only cue for getting the reward. Otherwise, various kinds of timing behavior were elicited which remained for long periods and led to long periods of training. It took 2 weeks - 1 month to establish the fixation behavior.
After the above training was completed, a cylinder (20 mm diameter) for attaching a microelectrode positioner was implanted in the skull under Sernylan (phencyclidine hydrochloride) anes- thesia. Bolts and nuts specially designed for restraining the monkey's head were also anchored to .the skull. These implants
were all made of Ni-Co-Mo alloy (Nippon Kinzoku, 22A) which was formed for orthopedic use to elicit negligible reactions by the animal's tissue.
The experiments to examine the visual properties of prefron- tal neurons were started 2 weeks or more after the surgery when any damage of the brain due to surgery had been virtually recovered from. To control infection, Kanamycin sulfate (Banyu) was injected into the animal once a day.
Presentation of Receptive Field Stimulus
In the experimental sessions, the monkey was seated in a primate chair with his head immobilized by the implanted bolts, perform- ing the fixation task. During maintained fixation of the center spot, a second light (RF spot) was projected via a double galvanometer mirror system onto various parts of screen (90 x 90~ The second light was used to define the RF of neurons under study. It was usually a round spot, presented 0.5 s after a lever- press and lasting for 1 s. Its rise time was reduced to 5 ms by a feed-back circuit. Neutral density filters were used so that its intensity level was kept at 1.0-1.5 log units above background.
While the center spot remained on, the monkey usually maintained fixation until the brightened, and made no eye movements toward the second spot. The eye position was moni- tored as horizontal and vertical electroculograms (EOGs). Inap- propriate eye movements occurring during the fixation period were detected by means of EOGs, and the trial was terminated automatically by an interposed 3 s time-out, a 5 ~ red-spot appear- ing in the center of the screen.
Stimulus generation, sequential control of the manipulandum during the trials and the presentation of RF light were carried out by a programmable controller developed in our laboratory.
Unit Recording and Data Processing
For recording unit activity, a microelectrode positioner (Narishige, MO-9) was attached to the implanted cylinder. With this device we could insert a glass-insulated Elgiloy microelectrode (Suzuki and Azuma 1976, 1979) through the intact dura into a desired location of the prefrontal cortex. The electrode had a sharp tip which was exposed 15-25 Ixm from the electrode insulation. Care was taken to sterilize the electrode, instruments and wound area. Typically, one penetration of the microelectrode into the cortex was under- taketi dally with a series of penetrations made at 1 mm intervals.
Unit activities were conventionally amplified and passed through a window discriminator. The converted pulses, together with EOGs and event signals, were fed into an interface led into a Nippon Data General 01 computer. Signals were processed on-line and shown on a computer display terminal (Tektronix, 4010-1) as raster patterns and peristimulus time histogram with respect to behavioral or stimulus events. A printed copy of this display was made by means of a Tektronix 4361 hard copy unit. Signals were also monitored on an oscilloscope and stored on a seven-channel FM tape recorder (Shinko, RCD-926H) for later analysis when necessary. Statistical analysis was made using a Nova 3 computer system.
When the dura was thickened after the lapse of time following surgery and the microelectrode could not readily penetrate it anymore, the monkey was reanesthetized and the granulation tissue on the dura was surgically removed under a binocular microscope. Granulation tissue could be almost completely removed leaving the dura intact. When all penetrations were finished at one cylinder site, the cylinder was sometimes moved to an adjacent part of the skull for exploring a new penetration area, or another cylinder implanted over the opposite hemisphere.
H. Suzuki and M. Azuma: Topography of Prefrontal Neurons 49
After the experiments were finished, the animal was killed with Nembutal injection. Then, the brain surface was marked by electrolytic deposition of iron at four selected points near the rim and the center of the recording cylinder. The brain was perfused through the heart with saline, followed by formalin solution containing ferrocyanide, and then removed. The iron-marked places were colored by the Prussian blue reaction. The sites were plotted as point of known coordinates on a photograph of the brain surface. Using these landmarks, the electrode penetrations on the cortical surface were transfered into the corresponding points on the photograph. The sulcus was also used as a landmark because it was recognized by the depth of the first appearing unit activity on electrode penetration.
Some of unit recording sites were marked by electrolytic deposits of iron from the tip of the glass-insulated Elgiloy microelectrode (Suzuki and Azuma 1976, 1979). The removed brain was further hardened in the formalin solution, frozen and cut into 50 ~m thick sections. The marked recording site was evi- denced by the approximately 150 pJn blue spot that was also sometimes surrounded by a proliferation of glial cells. Sections were stained with cresyl violet for identification of the marked sites.
Sampling of Visual Responses
While the monkey was actively fixating on a small, dim center spot, the microelectrodes were inserted 0 ~ for a total of 757 times into ten prefrontal cortices. This was done while monitoring background neu- ronal noise with an audio-amplif ier and speaker as well as making observations on the oscilloscope. When the noise changed due to RF-spot stimulation, we moved the electrode up-and-down very carefully to isolate unit activities that responded to the RF- spot stimulus. When isolating multiunit activity from a cluster of a few neurons, the largest one was selected by means of the window discriminator. By this means we were able to isolate 304 visual neurons that showed clear responses to the RF-spot stimulus. The micrometer measure of the electrode drive indicated that such visually-responding neurons were located in the superficial layers of the cortex. This corresponded to the findings that the majority of marked visual neurons was found to be located in the second and upper third layers (Fig. 1). Since we usually marked the first encountered visual neurons on electrode penetrat ion from the surface, the occurrence of units in our data might be biased to superficial layers of the cortex. The following obser- vation may, however, further support our finding. Sometimes the electrical activity of the superficial layers was depressed, probably as a result of damage due to electrode penetration. In such cases, we hardly obtained any neurons showing visual re- sponses.
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I II IV V ~I
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Fig. 1A, B. Laminar distribution of marked visual neurons in the prefrontal cortex. A Examples of electrode mark sites where visual neurons were recorded. Short bar, 0.4 mm. B Laminar distribu- tion of visual neurons which were identified by electrode marking. Notice the large portion of visual neurons distributed in the upper cortical layers
In the course of recording neuronal activity, we often found two or more units responding to the visual stimuli. Thus, the visual neurons seemed to discharge to some degree in common in this area of the cortex. However, the present method of unit recording did not offer a means to assess the exact percentage of visual neurons discharging within the whole of the neuron population of the area.
Figure 2A, B gives an example of the responses of the visual neurons ,of the prefrontal cortex. This particular neuron showed virtually no change in discharge rate during active fixation of the small center spot (Fig. 2A). In contrast, it was vigorously activated by the RF stimulus illuminating the appro- priate locus in the visual field (Fig. 2B). Thus, we
50 H. Suzuki and M. Azuma: Topography of Prefrontal Neurons
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