Electrical stimulation of occipital lobe can produce the perception of phosphenes, bright spots in the visual field1
. Phosphenes have been proposed to be a fundamental unit of visual perception, and may provide the building blocks for cortical prosthetics for the treatment of blindness2
. In a previous study, we electrically stimulated identified human visual areas and found that only some areas supported phosphene perception3
. The relationship between activity in visual cortex and visual perception is a matter of intense debate4
. In order to search for the neural correlates of perception, in the present study we stimulated or recorded from 214 electrodes in 3 subjects.
In an initial screening step, individual electrodes were electrically stimulated and subjects verbally reported whether they perceived a phosphene. Across three subjects, 16 electrodes produced a phosphene (“percept electrodes”) and 128 electrodes did not produce a phosphene (“non-percept electrodes”); the remaining electrodes were not screened. Percept electrodes were concentrated over early visual areas near the occipital pole () consistent with previous reports1,3
. Following screening, one percept electrode and the nearest non-percept electrode (both positioned on occipital cortex) in each subject were selected for experiment 1. Single 5 ms current pulses (1–1.5 second interpulse interval) were repeatedly delivered to these electrodes. The same stimulation current was used for the percept electrode and the non-percept electrode in each subject; the current was sufficient to always produce a phosphene in the percept electrodes. Subjects were instructed to remain alert but did not perform a behavioral task. Time-locked to delivery of the electrical pulses, neurophysiological data were collected from all non-stimulated electrodes. Neural oscillations in the gamma range (~ 30–200 hz), have been found to reflect neuronal spiking activity5,6
and may serve as a general mechanism of information processing7
. Comparing the gamma activity evoked by percept and non-percept electrode stimulation revealed a surprising pattern (): a much greater response was observed in and around the temporoparietal junction (TPJ) for percept vs.
non-percept stimulation. We selected the electrode closest to the TPJ in each subject for further analysis. When percept electrodes were electrically stimulated, a burst of high-frequency (60–150 hz) gamma activity was observed in the TPJ () beginning within 100 ms after stimulation onset and continuing for 200 ms. Non-percept electrode stimulation at the same current produced no such TPJ activity. To quantify this effect, we performed a two-factor ANOVA with stimulation electrode type (percept vs.
non-percept) as the fixed factor, subject as the random factor and TPJ gamma response (relative to pre-stimulation baseline) for each stimulation pulse as the dependent measure. A significant effect of stimulation electrode type was observed (F1,237
= 64, p = 10−13
). Across subjects, the gamma power increased 54% ± 6% (mean ± SEM) with percept electrode stimulation vs.
−3% ± 3% with non-percept electrode stimulation. To determine if the effect was specific to high-frequency gamma power, we performed a similar ANOVA with TPJ low-frequency power (1 hz–30 hz) following stimulation as the dependent measure. A small difference was observed in low-frequency power (8% ± 5% vs.
−7% ± 5%, F1,237
= 4, p = 0.04).
Figure 1 A. Percept electrodes (green) that produced a phosphene upon electrical stimulation and non-percept electrodes (red) that did not in three subjects. Subject 1 (s1) shows a posterior view of the right hemisphere; s2: posterior view of left hemisphere; (more ...)
To examine the consistency of the TPJ gamma power change, we plotted the TPJ gamma response to single trials (consisting of single 5 ms pulses) of occipital stimulation (). Single trials of percept electrode stimulation resulted in high TPJ gamma power, while single trials of non-percept electrode stimulation did not. We constructed a receiver operating curve (ROC) to test whether it was possible to discriminate between percept and non-percept trials based on the TPJ gamma response (). A high degree of discriminability was observed (mean d’ across subjects, 1.2). This suggests that the TPJ gamma activity carries information that an ideal observer could use in determining whether or not the subject perceived a phosphene.
The observation that TPJ gamma activity was present on trials in which percept electrodes were stimulated (and subjects perceived a phosphene) but not on trials in which non-percept electrodes were stimulated (and subjects did not perceive a phosphene) raises the possibility that TPJ gamma power might be causally related to visual perception. Another possibility is that TPJ gamma power was merely correlated with the location of electrical stimulation: high for stimulation of early visual areas (which tend to produce phosphenes) and low for late visual areas (which tend not to produce phosphenes)3
. To distinguish these possibilities, we capitalized on the observation that electrical stimulation of percept electrodes over early visual areas does not always produce a phosphene: the likelihood of phosphene perception increases with the stimulation current3
. Therefore, in experiment 2, we stimulated individual percept electrodes in the occipital lobe of each subject, but varied the stimulation current from trial to trial. At low stimulation currents, low levels of gamma power were observed in the TPJ; as the stimulation current increased, so did TPJ gamma power (). To quantify this effect, a two-factor ANOVA was performed with stimulation current as the fixed factor, subjects as the random factor, and TPJ response (relative to pre-stimulation baseline) in each stimulation interval as the dependent measure. A significant effect of stimulation current was observed (F3, 1236
= 47, p = 10−28
). To measure phosphene perception, subjects performed a two-interval forced-choice behavioral task that required them to report the interval containing electrical stimulation8
. At high currents, performance was nearly perfect, indicating that a phosphene was always perceived; at low currents, performance was near chance, indicating no percept. The relationship with increasing stimulation currents was similar for TPJ gamma power (neurometric function) and for behavioral performance (psychometric function) with monotonic increases in both variables ().
A. The average TPJ response during electrical stimulation of three percept electrodes in occipital lobe in s1 at varying stimulation currents (2–8 mA).
The similarity between the psychometric and neurometric functions supported the idea of a link between TPJ responses and perception. The null hypothesis is that while increasing currents led to both improved discrimination and increased TPJ gamma power, these were independent processes. To test this hypothesis we examined trials in the two-interval forced choice task in which the identical near-threshold current was delivered to a percept electrode. As expect, this level of current produced a mix of correct trials (in which subjects correctly detected the stimulation interval, suggesting phosphene perception) and incorrect trials (in which they did not, suggesting no phosphene perception). If TPJ gamma power was dependent on the amount of stimulation current but not related to perception, we would expect no power difference between correct and incorrect trials (because the stimulation current was exactly the same in each trial). An ANOVA was performed with trial type as the random factor, subject as the fixed factor, and TPJ gamma power in the stimulation epoch relative to pre-stimulation baseline as the dependent measure. Across subjects, a significant effect of trial type was observed (F1,465 = 26, p = 10−6) with greater power in correct than incorrect trials (99% ± 5% vs. 42% ± 9%), demonstrating a relationship between TPJ gamma power and perception (). It should be emphasized that the physical stimulation parameters in these two trial types were identical: the same electrode and same stimulation current. To examine the reliability of this effect, we examined individual correct and incorrect trials (). An ROC analysis of the individual trial data revealed a significant ability to discriminate correct from incorrect trials based on the stimulated-evoked TPJ gamma power (mean d’ across subjects, 0.74).
These results suggested that the gamma oscillations in TPJ might be a neural signature of the phosphene percept. If this was the case, an ideal observer could perform the two-interval forced choice task by comparing the TPJ gamma power across the two intervals within a single trial. To test this idea, we compared the TPJ gamma activity between stimulation and non-stimulation intervals within individual trials. Within correct trials, there was a very large TPJ power difference between the stimulated and non- stimulated intervals (99% ± 5% vs. 19% ± 3%, t374 = 14, p = 10−36). Within incorrect trials, there was only a small TPJ power difference between the stimulated and non- stimulated intervals (42% ± 9% vs. 20% ± 6%, t93 = 2.2, p = 0.03). An ROC analysis confirmed that an ideal observer could do very well at distinguishing the two intervals in correct trials (d' = 1.1) but not in incorrect trials (d' = 0.3). This suggests that the electrical stimulation of visual cortex on incorrect trials did result in TPJ gamma oscillations, but that the amplitude of the oscillations was below the neural threshold for perception, leaving subjects unable to discriminate the two intervals.
If TPJ gamma oscillations are critical for visual perception, disrupting them would be expected to interfere with perception. Therefore, in experiment 3 we electrically stimulated the TPJ while subjects detected visually presented sine-wave gratings in a gaussian window (Gabor patches). A preliminary test examined whether TPJ stimulation in isolation produced a behavioral effect: for instance, if TPJ stimulation produced a phosphene, this could hinder perception of gratings in an uninteresting way. In our initial screening, subjects did not report a phosphene following TPJ stimulation. As an additional check, we also performed a more sensitive two-interval forced choice task in which subjects attempted to detect TPJ stimulation; subjects performed at chance level on this task (49%; 95% confidence interval, CI, from the binomial distribution of 32% to 65%). Next, we tested subject's ability to detect the location of a grating randomly presented in either the left or right hemifield on each trial. At high contrast, subjects easily detected the grating, performing at ceiling (99%, CI 95% to 100%). At threshold contrast, subjects detected the grating on 58% of trials (CI 50% to 66%). Next, we electrically stimulated the TPJ while subjects performed the task; stimulation and non-stimulation trials were randomly intermixed. Subjects continued to perform at ceiling levels (99%, CI 95% to 100%) for high-contrast gratings, demonstrating that TPJ stimulation did not interfere with the ability to perform the behavioral task. However, for threshold contrast gratings, a significant effect of stimulation was observed. Detection was better for gratings presented ipsilateral to the stimulated TPJ than for gratings presented contralateral to the stimulated TPJ (76% vs. 53%, p = 0.03 from binomial distribution, CIs 66% to 85% and 42% to 63%). Relative to no stimulation, performance improved when gratings were presented ipsilateral to the stimulated TPJ (76% vs. 58%, p = 0.05) but was not significantly different for gratings presented contralateral to the stimulated TPJ (53% vs. 58%, p = 0.6).
Previous work demonstrated that electrical stimulation of some sites in visual cortex, but not others, produces phosphenes1,3
. In the present study, we combined electrical stimulation with electrical recording and found that subjects perceived a phosphene during electrical stimulation only when high-gamma power was recorded in the TPJ. TPJ activity during phosphene perception was observed both during passive stimulation (experiment 1) and while subjects performed a behavioral task (experiment 2) making it difficult to attribute the gamma activity to task performance. Our observation of visual perception related gamma activity in the TPJ is striking, because converging evidence suggests that the TPJ is critical for detecting behaviorally relevant stimuli 9
. The TPJ has been proposed as a neural generator for the P300 event-related potential, which is linked to target detection across sensory modalities10
. In particular, damage to ventral regions of parietal lobe, especially the TPJ, may cause difficulties in orienting to a meaningful stimulus presented contralesionally either alone (spatial neglect) or with a simultaneous ipsilesional stimulus (spatial extinction)11–13
. This suggests a possible parallel with our results in experiments 1 and 2. When electrical stimulation does not produce a phosphene, neural activity is produced at the electrode site, but it does not propagate through the cortical network to evoke TPJ activity, and hence fails to enter conscious awareness just as with neglected/extinguished visual stimuli. In contrast, when neural activity at the stimulation site does propagate to the TPJ, the activity enters conscious awareness and a phosphene is produced. Experiment 3 demonstrated that TPJ stimulation resulted in an altered ability to detect visual stimuli, with enhanced detection ipsilaterally and reduced detection contralaterally. These behavioral results are consistent with the hemispheric competition model of attentional control14
. If the TPJ in one hemisphere is disrupted, it becomes less able to detect stimuli in the contralesional hemifield, but also decreases its transcallosal inhibition of the contralateral TPJ, producing an ipsilesional attentional bias that can actually improve detection performance for ipsilesional stimuli15