Central phosphenes in man: A report of three cases

Neuropsychologin,

1973,

Vol.

11, pp.

1 to

19.

Pergamon Press.

Printed in

England.

CENTRAL PHOSPHENES IN MAN: A REPORT OF THREE CASES* N. P. CHAPANIS, S. UEMATSU, B. KONIGSMARKand A. E. WALKER The Johns Hopkins University School of Medicine, Baltimore, Maryland (Received 18 September 1972) Abstract-Chronic thalamic electrodes were implanted via the occipital lobe in three patients for the relief of intractable pain. Electrical stimulation of the electrode tract passing through the visual system led to the production of central phosphenes. These phosphenes were described as round, square, triangular, or rectangular. Some were white, some were patterned in black and white, and others were colored. Good visual angle constancy was demonstrated for one phosphene. Phosphenes were reliably evoked over the period of implantation. The temporal history of stimulation affected the location, brightness and threshold of the phosphene. The type of phosphene evoked by stimulation in the optic radiation area depends on the site of stimulation and the pulse frequency employed. Some phosphenes appear to move away from the fixation point, while others are stable for the duration of stimulation. IN 1968 BRINDLEY [l] reported

on the sensations

produced

by electrical

stimulation

of the

An array of 80 radio receivers was implanted under the patient’s skin and connected through a hole in the patient’s skull to platinum electrodes placed in contact with the occipital pole of the right cerebral hemisphere. With this device Brindley was then able to explore for a period of six months or SO many aspects of the relationship between the electrical stimulus and the resulting sensations. He found that stimulation of a single electrode most often led to the sensation of a single spot of white light at a constant position in the visual field. His most provocative finding was that simultaneous stimulation of several electrodes caused the patient to see predictable simple patterns. On this basis, he argued that it should eventually be possible to build a visual prosthesis that would enable the blind to see. The reports of phosphenes with electrical stimulation of the occipital cortex is certainly not new. One of the first clinical studies of stimulation of the striate area of the occipital cortex was carried out by LOWENSTEINand BORCHARDT [2] as long ago as 19 18. Later KRAUSE [3] observed that when stimulating certain points on the occipital cortex his patient reported a small spot of light ac a fixed position in the appropriate visual field. Over the following years there were sporadic attempts at correlating brain stimulations and sensations, but with the advent of neurosurgical procedures for the treatment of epilepsy, cortical mapping became a mandatory part of the operative procedure itself. In PENFIELDand RASMUSSEN’S [4] summary of their 15 years’ experience in stimulating the cortex of conscious patients during such operative procedures there is mention of the stimulation of occipital and nearby areas and the visual sensations evoked, More recently, MARC and DIERSSEN[5] reported their observations of 20 cases in which the human brain was stimulated with microelectrodes. All of these concern acute stimulation experiments which are seriously

surface

of the visual

cortex

of a recently

blinded

woman.

*This research was supported by Contract No. NIH-70-2277 from NINDS. Some preliminary findings were presented at the Eastern Psychological Association meeting in 1971. A summary of this paper was presented at the American Neurological Association meeting in Chicago 1972. 1

2

N. P. CHAPANTS,S. UEMATSU,B. KONIGSMARKand

A. E. WALKER

by the available time and thus pose difficulties in obtaining quantifiable data. Brindley, of course, avoided some of these problems by using chronically implanted electrodes. WALKER and MARSHALL [6] developed a quite different technique for chronic electrical stimulation and depth recording in man. They took a tress of fine insulated wires, threaded them into a guiding needle, and inserted the needle into the brain via a burr-hole in the skull. When the needle was removed, the wires were left in place for both depth recording and chronic depth stimulation. Over a decade of clinical experience with such a method of implantation and stimulation of epileptic patients indicates that it is a practical, useful, and safe procedure. For some time neurosurgeons have been making lesions in the thalamus for the relief of intractable pain, such as that due to terminal cancer. Thermocoagulation of the thalamus may only be carried out after the location of the thalamic probe has been verified by a series of threshold stimulations. This may be done over a period of some days with the use of chronically implanted depth electrodes. If the thalamic probe is inserted via an occipital drill-hole and if an array of electrodes is attached to the shaft of such a probe, then, while thalamic thresholds are being mapped, sections of the central visual pathway may al’s0 be stimulated in consenting patients. The systematic study of the visual sensations evoked by stimulations of the central visual pathways is the topic of this paper. limited

METHODS Patients with intractable pain were referred to the Johns Hopkins Hospital Neurosurgical Service after more conservative measures failed to relieve pain. They were offered the possibility of a therapeutic thalamic lesion. These patients had the procedure described to them and the experimental aspects defined. Some patients declined this procedure, but four consented and were implanted during the course of one half year. In one patient the el-ctrodes were almost immediately removed for medical reasons, before data could be collected and the case will not be discussed further. _ Case 1 was a 56-vear-old white male who suffered from intractable right-hio 1. oain due to a bladder carcinoma which had metastasized to the pelvis and hip. The depth electrodes remained implanted for eighteen days. Case 2 was a 52-y:ar-old whiie female with constant severe pain of the left side of the chest and shoulder, secondary to breast carcinoma which had metastasized to the cervical spine. The period of electrode iniplantation was twenty days. Case 4 was a 32-year-old white female with involunrary dystonic movements of the neck, trunk and extremities, and marked flexor contraction of all joints. In addition, the patient experienced pain with joint movement and was unable to walk. The electrode tress was removed twenty days after implantation. Operative procedure A thalamic depth electrode proSe was implanted under local anesthesia through an occipital drill-hole just above the inion. For cases 2 and 4 it was inserted 12 mm laterally from the midline, and for case I, 25 mm away. A 14 gauge 22 cm needle was used to guide the insertion of the electrode tress into the brain with X-rays used to monitor the positioning. For cases 1 and 2, the tip of the probe was placed in the centrum medianum; for case 4, in the ventrolateral nucleus of the thalamus. When the tress was correctly posilioned, the guiding needle was removed leaving the wires in place. The drill-hole was closed with gauze and the wires later soldered to a plug located outside of the scalp. The patient wore this plug for the period of implantation without discomfort and in no way impeded in normal daily chores. Psychophysical procedure The patient was generally well recovered from the operative procedure by the second or third day. Testing was carried out in two connecting rooms. The patient sat in a comfortable chair in an electrically shielded room with the electrode tress hooked up and passed via a cable to an outside room which contained the stimulator and 16-channel EEG recording equipment. There were four experimenters: two inside with the patient and two outside with the equipment. The patient sat with his back to a small glass window located

CENTRAL

PHOSPHENES

IN MAN

3

in one wall of the testing room. A built-in microphone inside the testing room relayed all verbal communication to those outside, while the glass window permitted two-way visual communication. In addition, all proceedings were tape recorded. Electrical stimulation was carried out daily for about 7-13 days, with each session lasting about two hours and involving from about 30-60 separate stimulations. Only rarely was a contact pair stimulated more than 10 times in one day. An EEG recording was made from the implanted depth electrodes for a short period of time immediately following each stimulation to monitor possible seizure activity. The patient was tested under two main conditions: In one he sat looking at a black semihemispheric perimeter in which the fixation point and crossbars were indicated with white surgical tape affixed to the black cloth background. In the other condition he sat looking at a pad of white paper on which a fixation point and crossbars had been drawn in black ink; the pad was positioned vertically on a stand within arm’s reach of the patient. The two experimenters in the outside room controlled the onset of stimulation, the contacts being stimulated, and the EEG recording. Of the two experimenters inside with the patient, one kept a log of the behavior of the patient and correlated it with elapsed time and onset of stimulation, while the other was in charge of all communication with the patient. A wall-mounted electric clock with a large second-hand sweep, visible only to the outside experimenters, was used to time the interval between stimulations. An upraised hand was the signal that stimulation was soon to begin, and the experimenter inside alerted the patient by asking him to look at the fixation point. The drop of the hand indicated the onset of stimulation. The patient could not see this visual signalling. Successive stimulations during each day were numbered consecutively and this information was relayed to the inside experimenters by hand signals. The experimenter working with the patient was unaware of the contacts being stimulated. A new order of stimulation of contact pairs was generated for each day. The determination of this order followed standard psychophysical practice with the stipulation that all contacts were to be stimulated before the series was repeated, and that successive contacts be chosen in such a way that there was a maximum spatial separation along the electrode tress. The order of stimulation remained the same for any one day but was reversed and otherwise counterbalanced on subsequent days. A train of pulses was automatically administered for 5 sec. The time interval between successive stimulations was always at least 1 min, and most often closer to 2 min. Stimulation was generally begun at low intensities and increased until a visual response occurred. On the average, a contact pair was stimulated at suprathreshold levels four times during each testing session. Discovering what a patient sees on stimulation is as difficult as trying to determine exactly how a person imagines a scene. Suprathreshold stimulation produced an immediate and clear sensation, so obvious that some patients were sure others in the room could also see it, even though intellectually they knew otherwise. The task, therefore, was to get the patient to describe what was so obvious in as full and detailed a manner as possible without, of course, suggesting anything. This was done in three ways: 1. Verbal report. The patient was asked to begin describing the evoked sensation as soon as it appeared. No questions were asked until he was finished. All verbal communications were tape recorded and verbatim transcripts made. These were correlated with the behavioral log of events. 2. Visual recall. The patient was asked to recall the size, shape and location of the phosphene in visual space. This was accomplished in two ways. In one, he directed the experimenter in the reconstruction of the phosphene; various shapes and sizes of phosphene were cut from surgical tape and attached to the black cloth background according to the patient’s specifications. When the patient was satisfied, the measurements were transcribed into a log. In the other, the patient drew the phosphene himself on the white pad. In some instances, the patient began the drawing before the phosphene had disappeared, but in most cases he relied on immediate memory after the event. Quantification of these data was done at leisure after the stimulation session. 3. Comparison with a standard. When the phosphene was colored, the patient was asked to match the color with one of a series of Munsell color chips. The patient had to make a number of alternative choices for the closest match to the color he saw. This was a comparison based on immediate memory. Depth electrode probe Each probe contained a tress of between 8-20 insulated wires of two types: one for the thermocoagulation of the thalamus (two wires), and a second for electrical stimulation of the visual system (6 to 18 wires). The stimulating electrodes for the visual system were made of no. 38 insulated stainless steel wire (WFormvar, 0.004 in., Johnson Mathy Co.). The insulation on each of these wires was scraped away in a 1 mm ring in such a way that the exposed portions of the wires in the tress were staggered at 7 mm intervals. The wires were tested electrically for leakage before being threaded through a needle and sterilized. The contact points were numbered consecutively with 1 being the deepest, 2 the next deepest and so on, to the surface of the brain. Electrical stimulation Electrical stimulation was provided by a square wave generator producing biphasic signals. This stimulator had built into it an override safety mechanism such that when current was held constant, the voltage

4

N. P. CHAPANIS,S. UEMATSU,B. KONIGSMARKand A. E. WALKER

could not rise beyond 20V and when voltage was held constant, the current could not go beyond about 3 mA. All stimulation was biphasic and was automatically timed to last 5 sec. Monopolar stimulation was attempted but patients complained. They were aware of the onset of each stimulation by a tingling or burning in the area of the skin used as an indifferent electrode. Therefore, bipolar stimulation of adjacent contact points was employed throughout this study. The parameters of stimulation were as follows. Pulse frequency: 80 pps, 160 pps, and 320 pps. Pulse width or duration: 0.25 msec, 0.5 msec, and 1 msec. The interphase interval was set at 0.1 msec except for a few instances in which it was changed to 0.25 msec. Current could be set at 0.25 mA, 05 mA, and 1 mA to 3 mA. Voltage could be varied in 1 V steps from 2 V to 20 V. Neuropathological

procedure

Two of the patients, Cases 1 and 2, had terminal cancer with a short life expectancy. Their brains were made available at autopsy. These were sectioned frontally and one cm thick blocks of occipital lobe were embedded in celloidin and stained with hematoxylin and eosin, cresyl violet, and Loyez myelin methods.

RESULTS The results can be grouped into two main sections. First, the autopsy logical findings ; and second, the psychophysical findings.

and neuropatho-

Autopsy and neuropathological$ndings Case 1 (Autopsy no. 37221) : At auptosy the bladder wall was infiltrated with transitional cell carcinoma. There were multiple bony metastases, particularly in the pelvis, vertebrae, and the base of the skull including the cavernous sinus and orbit. There was an extensive bronchopneumonia with terminal aspiration of gastric contents. The exterior surface of the brain was normal. The point of entry of the electrode tract, in the left posterior occipital lobe, was 25 mm from the midline. The tract, seen in frontally cut histological sections, impinged on the lateral occipital cortex (Fig. 1 (A) a, b). It coursed rostrally, contacting the lateral part of the geniculo-calcarine tract about 30 mm after entry into the brain (Fig. 1 (A) c). Over the next 10 mm it coursed into the lip of the rostra1 calcarine cortex (Fig. 1 (A) d), entering then the posterior horn of the lateral ventricle, and finally ending in the thalamus. Stimulation of contacts 7-8 evoked a visual sensation and these two contacts were located in a portion of the geniculo-calcarine tract (Fig. 1 (A) c, d). A reconstruction of the location of the electrode tress (1) appears in the left hemisphere of the brain in Fig. 2. Case 2 (Autopsy no. 37502): At autopsy there were multiple metastases of breast carcinoma to bones and to liver. There was also a moderate bronchopneumonia, contributing to death. The brain was grossly normal except for minimal atrophy. The electrode tract entered the right occipital pole 12 mm from the midline. At a depth of 15 mm (Fig. 1 (B) a) the tract contacted the midlayers of the lingual cortex, just ventral to the calcarine cortex. About 10 mm rostra1 to this (Fig. 1 (B) b) the tract continued 10 mm ventral to the calcarine cortex, involving the lingual subcortical white matter. Seventeen mm rostra1 to this and 42 mm from the entry point, the tract was found 10 mm below the calcarine cortex, involving the superficial lingual cortex on the tentorium cerebelli (Fig. 1 (B) c), but it could not be identified in the next block. It probably entered the superficial leptomeninges of the rostra1 lingual gyrus, for there were a few macrophages and fibroblasts in the meninges at this level. This electrode passed about 1 cm below the calcarine cortex and geniculo-calcarine tract involving for the most part the lingual gyrus and association areas from the visual cortex. A reconstruction of the location of the electrode tress (2) appears in the right hemisphere of the brain in Fig. 2. Case 4. This patient did not come to autopsy.

CENTRAL

PHOSPHENES

IN MAN

FIG. 2. Schematic reconstruction of the electrode tracts for Case 1 and Case 2, showing (a) lateral, (b) posterior, and (c) dorsal views of a brain. The electrode tract for Case 1 is shown by (1) in the left occipital lobe, coursing to the thalamus. The tract in Case 2 is shown by (2) in the right occipital lobe, coursing to the thalamus. The precise locales are seen in Fig. 1.

Psychophysicnljindings Electrical stimulation of contacts located within the visual system produced a variety of phosphenes which stabilized, after the first days, into reliable reports of sensations. Figure 3 illustrates the main sensations reported by each of the three patients. Case 1 had one active pair of electrodes, contacts 7-8 located in the geniculocalcarine tract (Figs. 1 and 2). Suprathreshold stimulation of this pair of electrodes resulted in the patient reporting a blue rectangle in the upper right quadrant when the surround was black and the ambient illumination weak (Fig. 3). When the surround was white and the ambient illumination relatively bright the color appeared bleached to a very faint bluish white. Case 2 had four active electrode pairs, contacts 4-5, 5-6, 6-7 and 7-8 located in the lingual gyrus and association areas from the visual cortex (Figs. 1 and 2). Individual stimulation of these four contact pairs produced “black and white” square or rectangular patterns appearing on the horizontal axis to the left of the fixation point (Fig. 3). The patient was able to identify consistently those stimulations which involved contacts 4-5 and 5-6, and to differentiate them from those involving contacts 6-7 and 7-8. Case 4 had six active contact pairs, contacts 7-8, 8-9, 9-10, 10-11, 11-12, and 12-13. In general, this patient saw a group of discrete bright white lights which she most often characterized as “Fourth of July fireworks”. This case was not a terminal cancer patient; she is still living, the pain much improved by the thalamic coagulation and she is now able to walk. The best estimate from X-ray studies is that contacts 7, 8 and 9 were in the anterior portion of the optic radiation and contacts 10, 11, 12 and 13 were in the mid-portion of the optic radiation area.

N. P. CHAPANIS, S. UEMATSU, B. KONIGSMARK ad

CASE*1 (CONTACTS

7-8)

A. E. WALKER

Bi(lGHT BLUE RECTANGLE

----I

INDISTINCT BLACK &WHITE PATTERN

CASEf;2 (CONTACTS

4-5)

FIXATION POINT

x

” BRIGHT JULY

CASE*4 (CONTACTS

FOURTH OF FIREWORKS”

9-10)

POINT

FIG. 3.

Main type of phosphene seen by each of the three patients. The phosphene on the side contralateral to the site of electrode implantation.

appeared

A total of about 1,100 stimulations were done on the three patients. Of these stimulations, about 500 involved non-productive contacts; the rest of the stimulations involved active contact pairs and evoked close to 300 phosphenes. The exact breakdown of stimulations for each patient and for each active contact pair is shown in Table 1. The percentage of phosphenes elicited by stimulation of each contact pair varies from 19 to 61 per cent, but this is not to be interpreted as necessarily indicating the sensitivity of each contact pair Table 1. Number of stimulations

Summary of all stimulations Number of phosphenes

for Cases 1, 2 and 4

Location of phosphene

Presumed location of contacts

Case 1 Contacts 7-8 Others Total

76 58 134

39 3 42

Upper right quadrant

Left geniculo-calcarine tract to visual cortex

Case 2 Contacts 4-5 5-6 6-7 7-8 Others Total

35 41 43 34 319 472

8 10 19 13 6 56

Left horizontal axis

Right lingual gyrus and association areas from the visual cortex

Case 4 Contacts 7-8 8-9 9-10 lo-11 11-12 12-13 Others Total

54 79 90 59 64 52 105 503

10

30 51 32 39 26 1 189

Upper left quadrant

Right anterior and mid-portion of the optic radiation area.

1109

287

Grand total

CENTRAL

PHOSPHENES

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IN MAN

since the number of below-threshold stimulations also varied for each of the contact pairs. Thus of the total of 90 stimulations for contacts 9-10 for Case 4, 28 were clearly subthreshold stimulations (at or below 0.25 mA), and 51 phosphenes were elicited by the remaining 62 stimulations. Also indicated in Table 1 is the location of the phosphene in the visual field and the presumed location of the active contacts in the visual system. All phosphenes were evoked on the side contralateral to the site of electrode implantation. Constancy of visual angle It has been hypothesized that evoked images or phosphenes would behave in the same way as after-images, that is, that the visual angle subtended by the phosphene should be constant. Such a hypothesis leads to two separately measurable phenomena. First, the closer the viewing surface to the eye, the smaller should be the size of the reported phosphene. Second, the closer the viewing surface to the eye, the closer should the phosphene appear to the fixation point. Within certain limits, this is indeed what happens. These two phenomena can be demonstrated with reference to the stimulation of Contacts 6-7 for Case 2. This contact pair was chosen for illustrative purposes because the phosphene was a square located along the horizontal axis from the fixation point, a factor which considerably simplified the calculation of the visual angle. Figure 4 summarizes the results of all 16” suprathreshold phosphenes obtained during the implantation period for three viewing distances and encompassing stimulation days 6, 7, 8, and 9. Phosphenes resulting from stimulation at all intensities at 160 pps of biphasic stimulation are included. In this figure, the size of the square (the horizontal width in cm) is plotted against the distance of the viewing surface from the eye (in ems). When the patient saw multiple squares, SIZE FUNCTION

OF

PHOSPHENE OF

VIEWING

AS

A

DISTANCE

CASE +=k 2 CONTACTS

6 - 7

160 pp5 I meeC PULSE BI PHASIC

L

0

80

40 VIEWING

FIG.

4.

120 D I STANCE,

160 cm

Width of square phosphene in Case 2 as a function of the distance of the viewing surface from the eye.

*Table 1 indicates that there were 19 phosphenes recorded for stimulation of contacts 6-7. However. 3 of these came from “double stimulation” by pairing with other inactive contact pairs, and they were therefore excluded from this particular analysis, leaving 16 phosphenes in all.

8

N. P. CHAPANIS,S. UEMATSU, B. KONIGSMARKand A. E. WALKER

only the square closest to the fixation point was utilized for the purpose of this graph. At distance D, the patient drew the phosphenes herself on a pad of paper and these remained as a permanent record of what she saw. For distances D, and D, adhesive tape was cut and attached to the background according to the patient’s specifications. The location and size of these perceived phosphenes were measured and recorded during the stimulation session. Inspection of the graph shows some sort of linear relationship between the size of this particular phosphene and the viewing distance. Figure 5 shows the location of the phosphene on the viewing surface (in terms of cm distance along the horizontal axis from the fixation point to the edge of the phosphene) at three viewing distances. The further away the viewing surface, the greater the distance between the perceived phosphene and the fixation point. There is, however, a great deal of variability in the location of the phosphene along the horizontal axis. Some of this variability may, in part, be a function of the temporal history of stimulation of a particular contact pair, a phenomenon to be described and discussed in the next section. DISTANCE

OF PHOSPHENE

FUNCTION

F.P. AS A

FROM

OF VIEWING

DISTANCE

CASE # 2 CONTACTS 6 -7 160 pps I msec PLJLSE 01 PHASIC

I

A

40 VIEWING

80

-

I

120 DISTANCE,

160 cm

FIG 5. Horizontal distance of the phosphene from the fixation point as a function of the distance of the viewing surface from the eye. The horizontal distance was measured from the center of the ftxation point to the nearest edge of the phosphene, that is, to the point of intersection of the phosphene with the horizontal axis.

The location and size of a phosphene can be used to calculate the visual angle subtended by the horizontal width of a phosphene. When the viewing surface is 41 cm away, the average width of the square is 1.05 cm, subtending an average visual angel of 1’30”, with the range between 1’49” and 1’16”. There is only one phosphene at 102 cm and it subtends a visual angle here of 1’25”. When the viewing surface is 150 cm away, the average width is 3.65 cm corresponding to a visual angle of 1’24”. Considering the apparent crudeness of our techniques the data reveal an extraordinary amount of reliability in the visual angle for this particular phosphene. Our data, therefore, are entirely consistent with the hypothesis that the visual angle subtended by a phosphene is indeed constant.

CENTRAL

PHOSPHENES

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IN MAN

Reliability of phosphene production There are a number of possible ways of estimating reliability of phosphene production. At suprathreshold values, the reliability of the phosphenes can be measured in terms of verbal identification, and, more precisely, by recall of appearance, location and brightness. These measures may be applied to three types of reliability: (a) within-session reliability; (b) stability over a span of days; and (c) reliability on rapid successive stimulation of the same contact pair. All three types will be discussed in turn. a. Within-session reliability. To get an estimate of within-session reliability, contact pairs have to be stimulated at exactly the same electrical parameters at least twice in the one testing session. The results of one such session for all four active contact pairs for Case 2 are presented in Fig. 6. The patient drew these phosphenes herself on a pad of paper held 41 cm away from her eye on the eighth day of stimulation. Tracings were made of the patient’s drawings and transferred to graph paper in such a way that the fixation points coincided on the right. There are two reproductions for each contact pair; these are numbered in the order in which they were stimulated on that particular day. CASE#Z. Day6 pps I m set Pulse 00 msecinierpnose 16 v

;50

++42

-t-

CONTACTS

7 - 6

CONTACTS

6 - 7

CONTACTS

5 -6

CONTACTS

4

lYr---lr--l~ ---.l-dL_.J, #49

-5

FIG. 6. Within-session reliability of phosphene production for Case 2 on Day 8. Tracings were made of the patient’s drawings and the drawings arranged so that the deepest contacts are at the bottom of the page. The drawings are to scale. The phosphenes evoked by contacts 6-7 and 7-8 are smaller and closer to the fixation point than those evoked from the deeper contacts 5-6 and 4-5. There are two examples of a phosphene from each contact pair, numbered in the order of stimulation for that day.

An inspection of the tracings indicates that the phosphenes are reasonably reliable in appearance and location when successive stimulations of the same contacts follow after an interval of not less than 7 min (each numbered stimulation was separated from the next by at least 1 min). The patient clearly distinguishes stimulations involving contact 5 from contact 7, both verbally and in her drawings. Both were “black and white” patterns but the smaller squares she had nicknamed “my picture” and the larger ones as “your

10

N. P. CHAPANTS,S. UEMATSU,B. KONIGSMARKand A. E. WALKER

diagonals”. Here is an excerpt from the tape recording for Day 8 for lations numbered 41-47 and encompassing stimulation of contacts 5-6, 9-10 and 6-7 in that order. Biphasic and bipolar stimulation at pulse duration, with 0.1 msec phase delay, was used in all cases. The taken from the log for that day.

one block of stimu3-4, 7-8, 4-5, 8-9, 160 pps and 1 msec action recorded was

Tape 915

Pt: NPC: Pt:

Is this the last one? No we have just another little one to go. O.K. Well, let’s get them done. Maybe I can hold out long enough, although 1 don’t have too much control. NPC: Alright, let me get myself organized. Here is your pencil. Alright Betty, we’re ready. Stimulation 41, Contacts 3-4: (No awareness of stimulation, no response) Stimulation 42, Contacts 7-g : (Patient begins to draw phosphene) Tape 927

NPC: Pt: NPC: Pt: NPC:

You see something huh? How about that. The black and white picture. Wish I could see what it was. That’s the black and white picture, you can’t tell? Uh huh. Alright, black and white picture. Alright, very good. Here we go. Alright, we’re ready. (Patient’s drawing numbered and replaced with another sheet). Stimulation 43, Contacts 4-5: (Patient begins to draw phosphene). Tape 935 NPC: You saw something

else? This is your thing. This is my thing? How about that. Can you describe it to me in words? What does it look like? Well. it’s black and white sort of diagonal lines, I can see that much. You ‘can see diagonal lines? Uh huh. Which way were they going? They were blocks with diagonals. They were blxks with diagonals? Uh huh, and I could see the black. In the lower right hand corner, 1 think. It sort of wasn’t very black but I could tell there was a difference from the others. NPC: There wasn’t very much of a contrast between them, huh? Right. But I could tell th-,re was a difference. Pt: NPC : Very interesting. How about that. That’s one for the record books, huh? Pt: I don’t know. I’d like to know a lot more about what you are doing. And then I wouldn’t make too good a subject would I? NPC: That’s true. O.K., we’re ready. (Drawing numbered and paper replaced). Stimulation 44, Contacts 8-9: (No awareness of stimulation, no response). Stimulation 45, Contacts 5-6: (Patient begins to draw). Pt: NPC : Pt: NPC: Pt: NPC: Pt: NPC: Pt:

Tape 953

NPC: Pt: NPC:

See something? Uh huh. Your thing. Oh, our thing. Out there, huh? Very good. And that’s the black and white diagonals? Alright, there we go. We’re ready. (Drawing numbered and paper replaced). Stimulation 46, Contacts 9-10: (No awareness of stimulation, no response). Stimulation 47, Contacts 6-7: (Patient begins to draw). Tape 968

NPC: Pt: NPC: Pt: NPC: Pt: NPC:

You see something. Which one is that? That’s the picture. This is the picture you can’t tell? Can’t tell what it is. I see, but it’s a black and white picture? O.K. You should make it bigger so I can tell. Oh, that’s marvellous. O.K. Alright, a little break on that one. Want me to move the ice bag? (short break).

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IN MAN

11

This excerpt illustrates a number of points about the stimulation, The patient’s perception of the phosphene is obvious and immediate. The drawing she makes conveys a lot of information, but so do her comments. Repeat sensations become so commonplace that she does not describe or draw them in great detail but merely identifies them. It is also true she did not give all the information she possessed. Aspects that she wasn’t sure of, she didn’t report. It was only at the end, when the electrodes were about to be removed, that the patient inquired shyly if the “indistinct picture” could have been a picture of a “house”; she wasn’t sure, but sometimes it did seem to her to be like that. She expected us to have the answer. b. Stability qf phospherzes. The first one or two stimulating sessions after threshold was established sometimes led to the production of visual effects that could not again be reproduced. Thus, Case 4 saw a “jagged” zigzag streak of “yellowish light” only on the first day of stimulation; Case 2 reported an ever-widening arc of a jagged zigzag light only on the second day threshold values were reached; and Case 1 reported vertical zigzag black lines superimposed on the blue rectangle only on the first day of stimulation. In addition, phosphenes were sometimes evoked by stimulation of some contact pairs and never again reproduced even when the same parameters and testing conditions were repeated. For example, in Case 2 there were four sets of stimulation of the contacts with the eyes closed or covered by light-resistant black goggles. Only one previously active contact pair produced a phosphene (“my black and white picture” to contacts 7-Q and she reported seeing “Lights, four bulbs, like headlights of a car” to the previously inactive contacts 15-16 when her eyes were both closed and covered by goggles. Those phosphenes evoked by stimulation of some contacts and not again consistently reproduced, are categorized as “others” in Table 1. For most contacts, however, there was generally good day-to-day reliability of phosphene production. It is a little difficult to document this precisely because the viewing distance and stimulus parameters were altered daily in order to test a wide sample of stimulus conditions. Nonetheless, the verbal identification of the various phosphenes remained constant. Summarized in Table 2 are samples of the verbal labels identifying the stimulation of a particular contact pair for each patient. Examples are given from the beginning, middle and end of the implantation period. For Case 1 the color specification remained about the same throughout the whole period of implantation (see Table 2). In Case 4, the patient began characterizing the lights she saw on Day 3 of stimulation as the “Fourth of July fireworks” and she continued to use this verbal description all the way through to Day 13 of stimulation (see Table 2). However, the brightness of the reported phosphene varied. For Case 2, the patient identified the phosphene as a “black and white picture” and this became her “indistinct picture” by the end of the implantation. The best evidence for the stability of this phosphene, however, is the constancy of the visual angle over a four day period of stimulation as described in the previous section. c. Reliability on rapid successive stimulation of the same contact pair. Previous work with depth electrode stimulation of epileptic patients had suggested that the time interval between successive stimulations of the same contact pair was very important. For this reason, the time between stimulation was controlled at the outset. In the first few days of investigation of Case 1 there appeared to be subtle changes in the reported phosphene with successive stimulations. It was therefore decided to carry out an experimental session in which suprathreshold stimulations would be administered in gradually decreasing time periods.

12

N. P.

CHAPANIS, S. UEMATSU, B. KONICSMARK and A. E. WALKER

Table 2. Stability of the verbal description Case 1: Contacts 7-8 Day 3: #6 Blue rectangle Hue 67.5 7 Brightness 4 or Saturation 6 I{

of the phosphenes

Day 5: #24 Blue rectangle 70.0 3 8

Case 2: Contacts 6-7 Day 6: #I9 Black and white picture flashed on momentarily (one square) Case 4: Contacts 9-10 Day 3: #I5 Whew! Where did that come from? Lights all over the place in the left hand corner. Real bright and quick. WhoIe corner full of dots. Bright lights. All contained in a circle. Big round dots of light. About the size of an eraser tip (of a pencil).

Hue Brightness Saturation

67.5 7 6

over the period of implantation

Day 6: #2 Blue rectangle Hue 67.5 Brightness 7 Saturation 6

70.0 716 6

Day 7: #23 Black and white blurred picture. Looks like a picture or something, but it is blurred (one square)

Day 9: #I8 My picture. It disappears as soon as I start talking (three squares)

Day 9: j/9 Fourth of July back with its glare.

Day 13: #20 Fourth of July, fairly bright but not too bright. Bright enough to make me blink but not blinding.

#21 Fourth bright.

#26 Wow! Very bright Fourth of July

of July, medium

The patient in Case 1 reported a blue rectangle located in the upper right quadrant on stimulation of contacts 7-8. At this particular testing session he sat strapped in a wheel chair facing a wall on which a black cloth had been draped and a white fixation point with white cross bars located at eye level. Stimulation was begun at slightly below threshold and after a five minute interval he was re-stimulated at an abovethreshold value. He saw a 6 x 0.4 cm blue rectangle located 1 cm above and 3 cm lateral to the fixation point. He was then told to rest. Seventeen minutes later he was stimulated again, and thereafter stimulated in decreasing time intervals until he was receiving a stimulation every two minutes. The patient was given a “ready” signal at varying short intervals before the stimulation. He reported seeing a phosphene immediately after the onset of stimulation and the phosphene apparently disappeared promptly at the end of stimulation. He directed the experimenter in locating the phosphene on the background, gave its size, and matched its color with the Munsell chips. Before the next stimulation all trace of the location of the previous phosphene was removed from the background on which it had been recorded. At the 9th stimulation, 38 min after the beginning of the experiment, he did not see the usual phosphene but reported “shooting lights” around the fixation point 100 set after stimulation. He saw phosphenes for the next two stimulations, but did not see any thereafter, even though the time interval was increased to 5 min. The experiment was ended after 53 min and after the 15th stimulation.

The size, shape and color of the phosphene did not change appreciably during this period of successive stimulations. What did change, however, was the location of the phosphene. It appeared to move diagonally away from the fixation point. Figure 7 illustrates what happened to this diagonal distance over time and over stimulations. Plotted along the ordinate is the shortest distance between the left-hand bottom corner of the rectangular phosphene and the fixation point. The time span from the beginning of the experiment to the end is indicated along the abscissa; the points of stimulation are shown by arrows. When the patient did not report a phosphene at stimulation, this is shown by an asterisk. The graph suggests that after a number of repeated stimulations some sort of “fatigue” had set in. The patient was completely recovered by the next day. Not only was the phosphene elicited by the same suprathreshold electrical parameters as had been used the previous day but it was also located in about the same original position. The experiment was replicated a week later for Case 1, and the same general effect was observed, that is, a stepwise

CENTRAL

PHOSPHENtS

13

IN MAN

REPEATED STIMULATION CASE NO. I IO

1

9E

u8 _

SHOOTING

LIGHTS

\1

(II -7c 6I :5 z4 : 32 20-J 0 I0

P 0

I L-----DELAYED I VISUAL *** * Xl 5

+

22 TIME

8

IN

27 30 34 40 MINUTES a hab4Ca6+9C

48

EF .FECT

I 53 4

STIMULATION

FIG. 7. Effect of repeated stimulation of contacts 7-8 in Case 1 on the diagonal distance of the phosphene from the fixation point. This graph shows that the temporal history of successive stimulations affects the perceived location and threshold of the phosphene. An asterisk indicates

stimulation but no phosphene. increase in the diagonal distance of the phosphene from the fixation point on rapid successive stimulation followed by a non-response. The same type of experiment using repeated stimulations was carried out with Case 4. when stimulated at contacts 9-10. The This patient saw “Fourth of July Fireworks” phosphene was located in the upper left-hand quadrant, and the patient outlined the area encompassed by these bright lights with a pen on a white paper background. On repeated stimulation, the shortest distance between this outline and the fixation point waxed and waned periodically (Fig. 8). The patient also mentioned that the lights varied in their brightness. Phosphenes which appeared closer to the fixation point tended to be called “bright”, whereas those furthest away were “dim”. For example, the first stimulation produced the following statement: “Fourth of July; like a flashbulb going off in my face”; was “real dim, hit twice”. the one at 15 min was “awful bright”, and the last stimulation It is not clear what is producing this overall effect on the perceived location of the phosphene with repeated stimulation. One possible explanation is that the patient is anticipating the appearance of the phosphene and shifting the eyes away from the fixation point. This is not, however, a very good argument. The patient is not aware of the exact moment of stimulation, nor, moreover, does he know what contact points will be stimulated. Even if the patient were aware, anticipation errors would lead to a random pattern of estimates around some point instead of a regularly fluctuating estimate. Furthermore, there is evidence from our data that all patients showed this fluctuation in distance from the fixation point whenever a contact pair was stimulated successively. It seems more reasonable to accept the patient’s word for the shift in apparent location and to look for some explanation in the interaction of the electrode, the stimulation and the brain tissue. There is no relationship between the length of time an electrode remained implanted in the brain and the shift in location of the phosphene. Nor is there any appreciable change in threshold for phosphene production during the period of implantation (apart from a

N.P.CHAPANIS,S.

UEMATSU, B.KONICSMARK

REPEATED

and A.E. WALKER

STIMULATION

CASE

NO.4

D EFFECT

0

5

IO

TIME 14

9

4

IN 4

15

20

25

MihUTES +

9

z

4

++c++

STIMULATION

FIG. 8. Effect of repeated stimulation of contacts 9-10 in Case 2 on the diagonal distance of the phosphene from the fixation point. This graph shows that the temporal history of successive stimulations affects the perceived location and brightness of the phosphene. In general, the phosphenes appearing closest to the fixation point were called “bright” while those further further away were “dim”.

small rise within the first few days). On the other hand, the shift in location seems to occur only when some critical time interval is exceeded in successive stimulation. If the successive stimulation continues long enough there is apparently a sudden change in threshold so that the phosphene is no longer evoked by the same stimulation parameters. This “fatiguing” effect, however, is reversible. The bulk of the evidence suggests that the apparent shift in location and sudden change in threshold is secondary to the passage of current through the brain tissue. The change for the may be due to neural or electrode “fatigue”, or both. The most likely explanation sudden change in threshold is that repeat stimulation leads to the production of gas bubbles around the electrode and that these bubbles raise the impedance and then slowly diffuse away over the next few hours. In any case, if sufficient time is allowed between successive stimulations, there is reliability in location of the phosphene and a maintenance of sensitivity to stimulation. EfSect of stimulation parameters on phosphene production Three types of stimulation parameters will be considered here: (a) location of electrode contacts; (b) effect of pulse frequency on thresholds; and (c) effect of pulse frequency on the nature of the evoked phosphenes. a. Location of electrode contacts. The active contacts in Case 4 pass through the anterior and midportion of the optic radiation area. Verbally and in drawings the patient made a a “cluster” of stationary lights, and a distinction between “Fourth of July Fireworks”, single triangular-shaped light that appeared to move or bounce to the left away from the she called it. These three types of phosphenes fixation-point-“my travelling diamond” are classified according to the contacts which evoked them in Table 3. Stimulation of the anterior portion of the optic radiation (contacts 7 through 9) most often produced the report of “Fireworks”. Stimulation of the midportion of the optic radiation (contacts 10 through 13), on the other hand, was more likely to lead to the report of a moving dot.

CENTRAL

PHOSPHENES

IN MAN

1.5

A &i-square analysis shows a highly significant relationship between stimulation contacts and the nature of the phosphene (Chi-square==89.8,

the location of the &=-lo, p
Table 3. Type of phosphene evoked by the six active contact pairs in case 4

-

Contact pair 7-8 8-9 9-10 IO-II 11-12 12-13 TOTAL Chi-square

Type of phosphene Stationery cluster 7 10 4 8 6 8 43

Moving dot 0 0 1 8 1.5 17 41

Fireworks display 3 20 46 16 18 1 104

= 89.8, elf = 10, pi 0.001.

b. Efict of pulse,frequency on thresholds. Alteration of the pulse frequency often, but not always, changed the threshold value for a particular contact pair. In general, higher pulse rate was associated with lower threshold. Illustrated in Fig. 9 are the threshold values obtained for all six active contact pairs in Case 4. Except for contacts 7-8, the threshold at 320 pps was lower than at 80 pps. The lowest constant current setting at which a response was obtained was 0.5 mA. Since we have only one measure of threshold at this particular combination of pulse duration and interphase interval, and since, furthermore, we have no definitive proof of the actual current delivered, these results should be considered as tentative. THRESHOLDS 0.5

m set

pulse

FOR

durotion,O.lmsec

CASE

*4

intcrphose

interval

CONTACTS

I

I

60 PULSE

FREQUENCY

12-13

PULSE

160

320

FREQUENCY

FIG. 9. Thresholds for the six active contact pairs in Case 4 as a function of the pulse frequency used.

The threshold measurements taken at other pulse duration and interphase interval values for Case 4 follow the same general pattern. So do the threshold measurements for Case 1.

16

N. P.

CHAPANIS,

UEMATSU,B. KONIGSMARKand A. E. WALKER

S.

The story is different for Case 2. Phosphenes were obtained only by stimulation at 160 pps. On a number of occasions, stimulation at 320 pps had the patient reporting, “Something is trying to get through, but as soon as I speak, it disappears.” The patient was told to signal the onset of a phosphene with an upraised finger instead of speaking, but it still did not work. She was unable to report any phosphenes at 320 pps. c. Effect ofpulsefrequency onphosphene characteristics. When the 188 phosphenes reported by Case 4 are categorized according to the pulse frequency used, a surprising and quite unexpected finding emerges (see Table 4). Stimulation at 80 pps most often gives rise to a moving dot or “travelling diamond”, while stimulation at 320 pps more often evokes the “Fireworks” display. A chi-square analysis of this distribution is highly significant (chisquare-54.05, df-4, p
== 54.05, df = 4, p < 0.001.

This effect may be illustrated by reference to the phosphenes evoked by stimulation of contacts 11-12. Of the 15 instances of a moving dot (Table 3), 13 occurred at 80 pps and none at 320 pps. On the other hand, of the 18 instances of a fireworks display (Table 3), 15 were produced by stimulation at 320 pps and only 1 at 80 pps. The differing character of these two sets of responses is illustrated in Figs. 10 and 11, tracings of the patient’s own CASE

N0.4,

CONTACTS

II-12

80

PPS 1 msec pulse 0.1 msec interphase 3mA

a0

0

)r ”

80 PPS 0.5 fnsec $;I, rsec

C

pulse interphase

FIG. 10. Moving dot phosphene evoked by stimulation of contacts 11-12 at 80 pps at two stimulation parameters. In the upper figure (Day 12 #40) the patient said: “Blinking light back again. One light moved to here and broke in half, becoming two lights.” In the lower figure (Day 12 #15) the patient said: “A speck of light that jumped three places right at the center line. Quick and medium bright.” All perceived phosphene movement was away from the fixation point along the left horizontal axis.

CENTRAL

PHOSPHENES

IN MAN

17

drawings. The “travelling diamond” is shown in Fig. 10 for two parameters at 80 pps stimulation. The area encompassed by the “fireworks” response at various intensities of stimulation at 320 pps is shown in Fig. 11. At the center is an illustration of what the patient called “a cluster of lights”. The size of the individual lights in the cluster is approximately the same as that of the “travelling diamond”.

FIG. 11. Stationery cluster of lights and fireworks display phosphenes evoked by stimulation of contacts 11-12 at 320 pps and at various constant current settings. These are tracings of the drawings the patient made.

COMMENT Depth electrode implantations in the visual system of man are capable of generating a considerable amount of data about central phosphenes produced by electrical stimulation. There are, however, some cautions to be observed in the interpretation of the data. All electrical stimulation of the brain is, to some extent, non-physiological. This raises two questions: Is there any damage of neural tissue at the site of stimulation? To what extent do central phosphenes evoked by electrical stimulation reveal the nature of the functioning of the visual system ? As nearly as we can tell, the electrodes for our three cases functioned well throughout the entire implantation period. When removed from the brains at the end of the implantation period the electrodes were reasonably free from any tissue or coagulum. None of the patients showed any visual field defects either during or after the stimulation studies. After a small rise in threshold during the first few sessions, the suprathreshold setting necessary to evoke a phosphene appeared reasonably constant throughout the rest of the implantation period. It would seem that at the functional level, visual areas that are being stimulated are performing at approximately the same efficiency at the end of the implantation period as at the beginning. The two autopsied brains showed very little in the way of macroscopic changes. In fact, it was even difficult to locate the point of insertion of the electrode shaft with the naked eye. Histopathologic studies of the tissue around the electrode course also revealed only the tract. It should be borne in mind that it is exceedingly difficult to pinpoint exactly the

18

N. P. CHAPANIS, S. UEMATSIJ, B. KONESMARK

and A. E. WALKER

tissue which surrounded the contact points of the electrode tract. The brain shrinks when it is embedded, so that exact measurements from X-rays cannot be strictly applied. Since serial sections were not done it is difficult to rule out damage by electrode stimulation. However, there was no damage in the sections examined beyond that expected from the electrode tract. A second concern for caution lies in the evaluation of the meaning of the phosphenes. The reports of the phosphenes are made by living, breathing, and thinking human beings. Whatever it is that is happening in the visual system as a result of the electrical stimulation is “interpreted” by the rest of the brain, and the interpretation is transmitted and communicated to the outside world via a drawing, a matching, or a verbal response. We are never just testing one particular area in the visual system; we are looking at the interaction between that stimulated area and the rest of the brain. Nevertheless, there is an implicit assumption that if we are entering a viable visual system with electrodes and triggering the usual inputs with electrical stimulation, then we ought to be getting data which match or simulate the normal activity of that section of the visual system. We depend on the patient to be able to report it to us as reliably as is possible. Changes in phosphene /ocatiotl An important unresolved question posed by our data concerns the changes in phosphene location reported by the patient. These changes are essentially of three kinds: the orderly fluctuation of the location on rapid successive stimulations; the appearance of multiple phosphenes; and the report of apparent movement of the phosphene in the visual field away from the fixation point. There are a number of possible explanations for each of these phenomena. It is possible, for instance, that the shift in location on successive stimulations may represent some sort of neural fatigue so that when the current dissipates beyond the fatigued area it activates the more distant tissue. This sort of explanation could also account for the fact that in Case 4, when the fireworks display appeared more distant from the fixation point on successive stimulation, it was also less bright. The appearance of multiple phosphenes and the apparent movement of phosphenes appear to be the result of a complex interaction of the location of the electrode, stimulation parameters, andmost importantly-eye movements, both voluntary and involuntary. It was not possible in this exploratory study to monitor for eye movements. Nevertheless, as nearly as we could tell by observing the patients’ eyes, some types of phosphene motion appeared in the absence of discernible eye movement, whereas others were accompanied by nystagmus. The untangling of these variables awaits quantification of eye movements during stimulation procedures. CONCLUSION As in all exploratory studies, the questions that are raised far exceed the definitive findings. Our study is no exception. Are there a finite number of basic colors evoked by the excitation of certainare as in the brain? How do we carry out a contour analysis of objects in our field of view ? How does color become the property of a particular object in space and where does this fusion of color and shape take place? What part do eye movements, voluntary and involuntary, play in the perception of phosphenes? How is it that in ordinary life we interpret the outside world as being stable and constant while it is our eyes, head, and body that moves through it? In short, how do sensations become perceptions? Perhaps the most valuable aspect of this study is the door it opens on the possibilitv of investigating what is happening at the central level when we say we “see”.

CENTRALPHOSPHENES IN MAN

19

REFERENCES 1. BRINDLEY,G. S. and LEWIN, W. The sensations produced by electrical stimulation of the visual cortex. J. Physiol:, Lond. 196, 479493, 1968. 2. LOWENSTEIN.K. and BORCHARDT.M. Svmptomatologie und elektrische Reizung bei einer Schussver_ letzung des Hinterhauptlappens. deut. Z;schr.f., Nerveih. 58, 264-294, 1918. 3. KRAUSE, F. and SCHUM, H. Neue Drufsche Chirurgie. H. KUTTNER. Editor. Vol 49 a, pp. 482-486. Ferdinand Enke, Stuttgart, 1931. 4. PENFIELD,W. and RASMUSSEN, T. The Cerebral Cortex of Man. Macmillan, New York, 1950. 5. MARG, E. and DIERSSEN,G. Reported visual percepts from stimulation of the human brain with microelectrodes during therapeutic surgery. Conjin. Neurol. 26, 57-75, 1965. 6. WALKER,A. E. and MARSHALL,C. Electrical stimulation of the brain. In StimrcLtion and Depth Recording in Man. Chapt. 35, D. E. SHEER(Editor). University of Texas Press, Austin, Texas. 1961. pp. 498-518. R&m&-On a implant& des electrodes thalamiques chroniques B travers le lobe occipital chez trois malades, dans le but de traiter des douleurs rebelles. La stimulation tlectrique des Electrodes passant g travers le systtme visuel determina des phosphknes. Ces phosphknes 6taient d&its comme ronds, car&, triangulaires:ou rectangulaires, quelques uns etaient blancs, quelques autres avaient des patterns noir et blanc et d’autres ttaient color&s. On a d&montr& une bonne Constance de l’angle visuel pour un phosphtne. Les phosphcnes ttaient &voquCs de faGon fiable pendant la ptriode de l’implantation. Les conditions temporelles de la stimulation modifient la localisation, la brillance et le seuil du phosphetne. Le type de phosphene tvoquC par stimulation dans l’aire des radiations optiques dCpend du sikge de la stimulation et de la frequence d’impulsion utiliste. Quelques phosphenes apraissaient s’kloigner du point de fixation tandis que d’autres sont stables pendant la durte de la stimulation. Zusammenfassung-Bei drei Patienten wurden zur Linderung unertrlglicher Schmerzen durch den Occipitallappen hindurch Dauerelektroden im Thalamus gelegt. Elektrische Stimulation der Elektrodenstrecke, die durch das optische System verlief, fiihrte zur Produktion zentraler optischer Reizerscheinungen. Diese Reizerscheinungen wurden als rund, quadratisch, dreieckig oder rechteckig beschrieben. Einige waren weia, einige schwarz und weip gemustert, und andere waren farbig. Fiir eine optische Reizerscheinung konnte eine gute Gesichtswinkelbestlndigkeit gezeigt werden. WIhrend der Dauer der Implantation waren die Reizerscheinungen zuverllssig hervorzurufen. Der zeitliche Ablauf der Stimulation hatte EinfluR auf die Lokalisation, die Helligkeit und die Schwelle der optischen Reizerscheinungen. Der Typ der Reizerscheinungen, der durch die Stimulation in der Sehstrahlung hervorgerufen wird, htingt von Ort und angewandter Frequenz des Reizes ab. Einige Reizerscheinungen scheinen sich vom Fixationspunkt wegzubewegen, wlhrend andere fiir die Dauer der Stimulation bestlndig sind.