Phosphene and motor transcranial magnetic stimulation thresholds are correlated: A meta-analytic investigation.

Transcranial magnetic stimulation (TMS) is commonly delivered at an intensity defined by the resting motor threshold (rMT), which is thought to represent cortical excitability, even if the TMS target area falls outside of the motor cortex. This approach rests on the assumption that cortical excitability, as measured through the motor cortex, represents a 'global' measure of excitability. Another common approach to measure cortical excitability relies on the phosphene threshold (PT), measured through the visual cortex of the brain. However, it remains unclear whether either estimate can serve as a singular measure to infer cortical excitability across different brain regions. If PT and rMT can indeed be used to infer cortical excitability across brain regions, they should be correlated. To test this, we systematically identified previous studies that measured PT and rMT to calculate an overall correlation between the two estimates. Our results, based on 16 effect sizes from eight studies, indicated that PT and rMT are correlated (ρ = 0.4), and thus one measure could potentially serve as a measure to infer cortical excitability across brain regions. Three exploratory meta-analyses revealed that the strength of the correlation is affected by different methodologies, and that PT intensities are higher than rMT. Evidence for a PT-rMT correlation remained robust across all analyses. Further research is necessary for an in-depth understanding of how cortical excitability is reflected through TMS.

Always expect the unexpected: eye position modulates visual cortex excitability in a stimulus-free environment.

Stimuli that potentially require a rapid defensive or avoidance action can appear from the periphery at any time in natural environments. de Wit et al. (Cortex 127: 120-130, 2020) recently reported novel evidence suggestive of a fundamental neural mechanism that allows organisms to effectively deal with such situations. In the absence of any task, motor cortex excitability was found to be greater whenever gaze was directed away from either hand. If modulation of cortical excitability as a function of gaze location is a fundamental principle of brain organization, then one would expect its operation to be present outside of motor cortex, including brain regions involved in perception. To test this hypothesis, we applied single-pulse transcranial magnetic stimulation (TMS) to the right lateral occipital lobe while participants directed their eyes to the left, straight-ahead, or to the right, and reported the presence or absence of a phosphene. No external stimuli were presented. Cortical excitability as reflected by the proportion of trials on which phosphenes were elicited from stimulation of the right visual cortex was greater with eyes deviated to the right as compared with the left. In conjunction with our previous findings of change in motor cortex excitability when gaze and effector are not aligned, this eye position-driven change in visual cortex excitability presumably serves to facilitate the detection of stimuli and subsequent readiness to act in nonfoveated regions of space. The existence of this brain-wide mechanism has clear adaptive value given the unpredictable nature of natural environments in which human beings are situated and have evolved.NEW & NOTEWORTHY For many complex tasks, humans focus attention on the site relevant to the task at hand. Humans evolved and live in dangerous environments, however, in which threats arise from outside the attended site; this fact necessitates a process by which the periphery is monitored. Using single-pulse transcranial magnetic stimulation (TMS), we demonstrated for the first time that eye position modulates visual cortex excitability. We argue that this underlies at least in part what we term "surveillance attention."

A Phosphenotron Device for Sensoric Spatial Resolution of Phosphenes within the Visual Field Using Non-Invasive Transcranial Alternating Current Stimulation.

This study presents phosphenotron, a device for enhancing the sensory spatial resolution of phosphenes in the visual field (VF). The phosphenotron employs a non-invasive transcranial alternating current stimulation (NITACS) to modulate brain activity by applying weak electrical currents to the scalp or face. NITACS's unique application induces phosphenes, a phenomenon where light is perceived without external stimuli. Unlike previous invasive methods, NITACS offers a non-invasive approach to create these effects. The study focused on assessing the spatial resolution of NITACS-induced phosphenes, crucial for advancements in visual aid technology and neuroscience. Eight participants were subjected to NITACS using a novel electrode arrangement around the eye orbits. Results showed that NITACS could generate spatially defined phosphene patterns in the VF, varying among individuals but consistently appearing within their VF and remaining stable through multiple stimulations. The study established optimal parameters for vibrant phosphene induction without discomfort and identified electrode positions that altered phosphene locations within different VF regions. Receiver Operating characteristics analysis indicated a specificity of 70.7%, sensitivity of 73.9%, and a control trial accuracy of 98.4%. These findings suggest that NITACS is a promising, reliable method for non-invasive visual perception modulation through phosphene generation.

Bypassing input to V1 in visual awareness: A TMS-EROS investigation.

Early visual cortex (V1-V3) is believed to be critical for normal visual awareness by providing the necessary feedforward input. However, it remains unclear whether visual awareness can occur without further involvement of early visual cortex, such as re-entrant feedback. It has been challenging to determine the importance of feedback activity to these areas because of the difficulties in dissociating this activity from the initial feedforward activity. Here, we applied single-pulse transcranial magnetic stimulation (TMS) over the left posterior parietal cortex to elicit phosphenes in the absence of direct visual input to early visual cortex. Immediate neural activity after the TMS pulse was assessed using the event-related optical signal (EROS), which can measure activity under the TMS coil without artifacts. Our results show that: 1) The activity in posterior parietal cortex 50 ms after TMS was related to phosphene awareness, and 2) Activity related to awareness was observed in a small portion of V1 140 ms after TMS, but in contrast (3) Activity in V2 was a more robust correlate of awareness. Together, these results are consistent with interactive models proposing that sustained and recurrent loops of activity between cortical areas are necessary for visual awareness to emerge. In addition, we observed phosphene-related activations of the anteromedial cuneus and lateral occipital cortex, suggesting a functional network subserving awareness comprising these regions, the parietal cortex and early visual cortex.

Mapping the routes of perception: Hemispheric asymmetries in signal propagation dynamics.

The visual system has long been considered equivalent across hemispheres. However, an increasing amount of data shows that functional differences may exist in this regard. We therefore tried to characterize the emergence of visual perception and the spatiotemporal dynamics resulting from the stimulation of visual cortices in order to detect possible interhemispheric asymmetries. Eighteen participants were tested. Each of them received 360 transcranial magnetic stimulation (TMS) pulses at phosphene threshold intensity over left and right early visual areas while electroencephalography was being recorded. After each single pulse, participants had to report the presence or absence of a phosphene. Local mean field power analysis of TMS-evoked potentials showed an effect of both site (left vs. right TMS) of stimulation and hemisphere (ipsilateral vs. contralateral to the TMS): while right TMS determined early stronger activations, left TMS determined later stronger activity in contralateral electrodes. The interhemispheric signal propagation index revealed differences in how TMS-evoked activity spreads: left TMS-induced activity diffused contralaterally more than right stimulation. With regard to phosphenes perception, distinct electrophysiological patterns were found to reflect similar perceptual experiences: left TMS-evoked phosphenes are associated with early occipito-parietal and frontal activity followed by late central activity; right TMS-evoked phosphenes determine only late, fronto-central, and parietal activations. Our results show that left and right occipital TMS elicits differential electrophysiological patterns in the brain, both per se and as a function of phosphene perception. These distinct activation patterns may suggest a different role of the two hemispheres in processing visual information and giving rise to perception.

Precise oculocentric mapping of transcranial magnetic stimulation-evoked phosphenes.

OBJECTIVE: Transcranial magnetic stimulation (TMS)-evoked phosphenes are oculocentric; their perceived location depends upon eye position. We investigated the accuracy and precision of TMS-evoked phosphene oculocentric mapping. METHODS: We evoked central phosphenes by stimulating early visual cortical areas with TMS, systematically examining the effect of eye position by asking participants to report the location of the evoked phosphene. We tested whether any systematic differences in the precision or accuracy of responses occurred as a function of eye position. RESULTS: Perceived phosphene locations map veridically to eye position, although there are considerable individual differences in the reliability of this mapping. CONCLUSIONS: Our results emphasize the need to carefully control eye movements when carrying out phosphene localization studies and suggest that individual differences in the reliability of the reported position of individual phosphenes must be considered.

Occipital alpha-TMS causally modulates temporal order judgements: Evidence for discrete temporal windows in vision.

Recent advances in neuroscience have challenged the view of conscious visual perception as a continuous process. Behavioral performance, reaction times and some visual illusions all undergo periodic fluctuations that can be traced back to oscillatory activity in the brain. These findings have given rise to the idea of a discrete sampling mechanism in the visual system. In this study we seek to investigate the causal relationship between occipital alpha oscillations and Temporal Order Judgements using neural entrainment via rhythmic TMS in 18 human subjects (9 females). We find that certain phases of the entrained oscillation facilitate temporal order perception of two visual stimuli, whereas others hinder it. Our findings support the idea that the visual system periodically compresses information into discrete packages within which temporal order information is lost. SIGNIFICANCE STATEMENT: Neural entrainment via TMS serves as a valuable tool to interfere with cortical rhythms and observe changes in perception. Here, using α-rhythmic TMS-pulses, we demonstrate the effect of the phase of entrained oscillations on performance in a temporal order judgment task. In extension of previous work, we 1. causally influenced brain rhythms far more directly using TMS, and 2. showed that previous results on discrete perception cannot simply be explained by rhythmic fluctuations in visibility. Our findings support the idea that the temporal organization of visual processing is discrete rather than continuous, and is causally modulated by cortical rhythms. To our knowledge, this is the first study providing causal evidence via TMS for an endogenous periodic modulation of time perception.

Inducing lateralized phosphenes over the occipital lobe using transcranial magnetic stimulation to navigate a virtual environment.

Electrical stimulation involving visual areas of the brain produces artificial light percepts called phosphenes. These visual percepts have been extensively investigated in previous studies involving intracortical microsimulation (ICMS) and serve as the basis for developing a visual prosthesis for the blind. Although advances have been achieved, many challenges still remain with implementing a functional ICMS for visual rehabilitation purposes. Transcranial magnetic stimulation (TMS) over the primary occipital lobe offers an alternative method to produce phosphenes non-invasively. A main challenge facing blind individuals involves navigation. Within the scientific community, methods to evaluate the ability of a visual prosthesis to facilitate in navigation has been neglected. In this study, we investigate the effectiveness of evoking lateralized phosphenes to navigate a computer simulated virtual environment. More importantly, we demonstrate how virtual environments along with the development of a visual prosthesis share a mutual relationship benefiting both patients and researchers. Using two TMS devices, a pair of 40mm figure-of-eight coils were placed over each occipital hemisphere resulting in lateralized phosphene perception. Participants were tasked with making a series of left and right turns using peripheral devices depending on the visual hemifield in which a phosphene is present. If a participant was able to accurately perceive all ten phosphenes, the simulated target is able to advance and fully exit the virtual environment. Our findings demonstrate that participants can interpret lateralized phosphenes while highlighting the integration of computer based virtual environments to evaluate the capability of a visual prosthesis during navigation.

Shape perception via a high-channel-count neuroprosthesis in monkey visual cortex.

Blindness affects 40 million people across the world. A neuroprosthesis could one day restore functional vision in the blind. We implanted a 1024-channel prosthesis in areas V1 and V4 of the visual cortex of monkeys and used electrical stimulation to elicit percepts of dots of light (called phosphenes) on hundreds of electrodes, the locations of which matched the receptive fields of the stimulated neurons. Activity in area V4 predicted phosphene percepts that were elicited in V1. We simultaneously stimulated multiple electrodes to impose visible patterns composed of a number of phosphenes. The monkeys immediately recognized them as simple shapes, motions, or letters. These results demonstrate the potential of electrical stimulation to restore functional, life-enhancing vision in the blind.

Extinguishing Exogenous Attention via Transcranial Magnetic Stimulation.

Orienting covert exogenous (involuntary) attention to a target location improves performance in many visual tasks [1, 2]. It is unknown whether early visual cortical areas are necessary for this improvement. To establish a causal link between these areas and attentional modulations, we used transcranial magnetic stimulation (TMS) to briefly alter cortical excitability and determine whether early visual areas mediate the effect of exogenous attention on performance. Observers performed an orientation discrimination task. After a peripheral valid, neutral, or invalid cue, two cortically magnified gratings were presented, one in the stimulated region and the other in the symmetric region in the opposite hemifield. Observers received two successive TMS pulses around their occipital pole while the stimuli were presented. Shortly after, a response cue indicated the grating whose orientation observers had to discriminate. The response cue either matched-target stimulated-or did not match-distractor stimulated-the stimulated side. Grating contrast was varied to measure contrast response functions (CRF) for all combinations of attention and TMS conditions. When the distractor was stimulated, exogenous attention yielded response gain-performance benefits in the valid-cue condition and costs in the invalid-cue condition compared with the neutral condition at the high contrast levels. Crucially, when the target was stimulated, this response gain was eliminated. Therefore, TMS extinguished the effect of exogenous attention. These results establish a causal link between early visual areas and the modulatory effect of exogenous attention on performance.

Theta Phase-dependent Modulation of Perception by Concurrent Transcranial Alternating Current Stimulation and Periodic Visual Stimulation.

Sensory perception can be modulated by the phase of neural oscillations, especially in the theta and alpha ranges. Oscillatory activity in the visual cortex can be entrained by transcranial alternating current stimulation (tACS) as well as periodic visual stimulation (i.e., flicker). Combined tACS and visual flicker stimulation modulates BOLD response, and concurrent 4-Hz auditory click train, and tACS modulate auditory perception in a phase-dependent way. In this study, we investigated whether phase synchrony between concurrent tACS and periodic visual stimulation (i.e., flicker) can modulate performance on a visual matching task. Participants completed a visual matching task on a flickering visual stimulus while receiving either in-phase (0°) or asynchronous (180°, 90°, or 270°) tACS at alpha or theta frequency. Stimulation was applied over either occipital cortex or dorsolateral pFC. Visual performance was significantly better during theta frequency tACS over the visual cortex when it was in-phase (0°) with visual stimulus flicker, compared with antiphase (180°). This effect did not appear with alpha frequency flicker or with dorsolateral pFC stimulation. Furthermore, a control sham group showed no effect. There were no significant performance differences among the asynchronous (180°, 90°, and 270°) phase conditions. Extending previous studies on visual and auditory perception, our results support a crucial role of oscillatory phase in sensory perception and demonstrate a behaviorally relevant combination of visual flicker and tACS. The spatial and frequency specificity of our results have implications for research on the functional organization of perception.

Semantic and structural image segmentation for prosthetic vision.

Prosthetic vision is being applied to partially recover the retinal stimulation of visually impaired people. However, the phosphenic images produced by the implants have very limited information bandwidth due to the poor resolution and lack of color or contrast. The ability of object recognition and scene understanding in real environments is severely restricted for prosthetic users. Computer vision can play a key role to overcome the limitations and to optimize the visual information in the prosthetic vision, improving the amount of information that is presented. We present a new approach to build a schematic representation of indoor environments for simulated phosphene images. The proposed method combines a variety of convolutional neural networks for extracting and conveying relevant information about the scene such as structural informative edges of the environment and silhouettes of segmented objects. Experiments were conducted with normal sighted subjects with a Simulated Prosthetic Vision system. The results show good accuracy for object recognition and room identification tasks for indoor scenes using the proposed approach, compared to other image processing methods.

Temporal Dynamics of Corticocortical Inhibition in Human Visual Cortex: A TMS Study.

Paired-pulse transcranial magnetic stimulation (ppTMS) has been used extensively to probe local facilitatory and inhibitory function in motor cortex. We previously developed a reliable ppTMS method to investigate these functions in visual cortex and found reduced thresholds for net intracortical inhibition compared to motor cortex. The current study used this method to investigate the temporal dynamics of local facilitatory and inhibitory networks in visual cortex in 28 healthy subjects. We measured the size of the visual disturbance (phosphene) evoked by stimulating visual cortex with a fixed intensity, supra-threshold test stimulus (TS) when that TS was preceded by a sub-threshold conditioning stimulus (CS). We manipulated the inter-stimulus interval (ISI) and assessed how the size of the phosphene elicited by the fixed-intensity TS changed as a function of interval for two different CS intensities (45% and 75% of phosphene threshold). At 45% of threshold, the CS produced uniform suppression of the phosphene elicited by the TS across ISIs ranging from 2 to 200 ms. At 75% of threshold, the CS did not have a significant effect on phosphene size across the 2-15 ms intervals. Intervals of 50-200 ms exhibited statistically significant suppression of phosphenes, however, suppression was not uniform with some subjects demonstrating no change or facilitation. This study demonstrates that the temporal dynamics of local inhibitory and facilitatory networks are different across motor and visual cortex and that optimal parameters to index local inhibitory and facilitatory influences in motor cortex are not necessarily optimal for visual cortex. We refer to the observed inhibition as visual cortex inhibition (VCI) to distinguish it from the phenomenon reported in motor cortex.

Frequency-dependent and montage-based differences in phosphene perception thresholds via transcranial alternating current stimulation.

It is well known that applying transcranial alternating current stimulation (tACS) to the scalp can generate artefactual visual perceptions of flashing or shimmering light known as phosphenes. The thresholds for generating these phosphenes have been used by international standards bodies to provide conservative estimates of the field strength required to interfere with human neural functioning and set safety limits accordingly. However, the precise relationship between electric currents and phosphene perception thresholds remains uncertain. The present study used tACS to systematically investigate the effects of the location and the frequency of stimulation on phosphene perception thresholds. These thresholds were obtained from 24 participants using a within-subject design as a function of scalp stimulation sites (FPz-Cz versus Oz-Cz) and stimulation frequency (2-30 Hz in steps of 2 Hz). Phosphene perception thresholds were consistently lower for FPz-Cz stimulation, and regardless of tACS location were lowest for 16 Hz stimulation. Threshold variation between participants was very small, which is meaningful when setting standards based on phosphenes. Bioelectromagnetics. 2019;40:365-374. © 2019 Bioelectromagnetics Society.

Efficiently searching through large tACS parameter spaces using closed-loop Bayesian optimization.

BACKGROUND: Selecting optimal stimulation parameters from numerous possibilities is a major obstacle for assessing the efficacy of non-invasive brain stimulation. OBJECTIVE: We demonstrate that Bayesian optimization can rapidly search through large parameter spaces and identify subject-level stimulation parameters in real-time. METHODS: To validate the method, Bayesian optimization was employed using participants' binary judgements about the intensity of phosphenes elicited through tACS. RESULTS: We demonstrate the efficiency of Bayesian optimization in identifying parameters that maximize phosphene intensity in a short timeframe (5 min for >190 possibilities). Our results replicate frequency-dependent effects across three montages and show phase-dependent effects of phosphene perception. Computational modelling explains that these phase effects result from constructive/destructive interference of the current reaching the retinas. Simulation analyses demonstrate the method's versatility for complex response functions, even when accounting for noisy observations. CONCLUSION: Alongside subjective ratings, this method can be used to optimize tACS parameters based on behavioral and neural measures and has the potential to be used for tailoring stimulation protocols to individuals.

Radiation Force as a Physical Mechanism for Ultrasonic Neurostimulation of the Ex Vivo Retina.

Focused ultrasound has been shown to be effective at stimulating neurons in many animal models, both in vivo and ex vivo Ultrasonic neuromodulation is the only noninvasive method of stimulation that could reach deep in the brain with high spatial-temporal resolution, and thus has potential for use in clinical applications and basic studies of the nervous system. Understanding the physical mechanism by which energy in a high acoustic frequency wave is delivered to stimulate neurons will be important to optimize this technology. We imaged the isolated salamander retina of either sex during ultrasonic stimuli that drive ganglion cell activity and observed micron scale displacements, consistent with radiation force, the nonlinear delivery of momentum by a propagating wave. We recorded ganglion cell spiking activity and changed the acoustic carrier frequency across a broad range (0.5-43 MHz), finding that increased stimulation occurs at higher acoustic frequencies, ruling out cavitation as an alternative possible mechanism. A quantitative radiation force model can explain retinal responses and could potentially explain previous in vivo results in the mouse, suggesting a new hypothesis to be tested in vivo Finally, we found that neural activity was strongly modulated by the distance between the transducer and the electrode array showing the influence of standing waves on the response. We conclude that radiation force is the dominant physical mechanism underlying ultrasonic neurostimulation in the ex vivo retina and propose that the control of standing waves is a new potential method to modulate these effects.SIGNIFICANCE STATEMENT Ultrasonic neurostimulation is a promising noninvasive technology that has potential for both basic research and clinical applications. The mechanisms of ultrasonic neurostimulation are unknown, making it difficult to optimize in any given application. We studied the physical mechanism by which ultrasound is converted into an effective energy form to cause neurostimulation in the retina and find that ultrasound acts via radiation force leading to a mechanical displacement of tissue. We further show that standing waves have a strong modulatory effect on activity. Our quantitative model by which ultrasound generates radiation force and leads to neural activity will be important in optimizing ultrasonic neurostimulation across a wide range of applications.

Perceptual and Physiological Consequences of Dark Adaptation: A TMS-EEG Study.

Existing literature on sensory deprivation suggests that short-lasting periods of dark adaptation (DA) can cause changes in visual cortex excitability. DA cortical effects have previously been assessed through phosphene perception, i.e., the ability to report visual sensations when a transcranial magnetic stimulation (TMS) pulse is delivered over the visual cortex. However, phosphenes represent an indirect measure of visual cortical excitability which relies on a subjective report. Here, we aimed at overcoming this limitation by assessing visual cortical excitability by combining subjective (i.e., TMS-induced phosphenes) and objective (i.e., TMS-evoked potentials - TEPs) measurements in a TMS-EEG protocol after 30 min of DA. DA effects were compared to a control condition, entailing 30 min of controlled light exposure. TMS was applied at 11 intensities in order to estimate the psychometric function of phosphene report and explore the relationship between TEPs and TMS intensity. Compared to light adaptation, after DA the slope of the psychometric function was significantly steeper, and the amplitude of a TEP component (P60) was lower, only for high TMS intensities. The perceptual threshold was not affected by DA. These results support the idea that DA leads to a change in the excitability of the visual cortex, accompanied by a behavioral modification of visual perception. Furthermore, this study provides a first valuable description of the relationship between TMS intensity and visual TEPs.

The Clinical Characteristics and Neurophysiological Assessments of the Occipital Cortex in Visual Snow Syndrome With or Without Migraine.

OBJECTIVE: Visual snow syndrome (VS) is mainly characterized by flickering, little dots in both visual fields. The recognition of the clinical entity of VS has been increasing recently. Diagnosis is based on patient reports and not better accounted for by another diagnosis. BACKGROUND: The exact pathophysiology of this syndrome is still unknown. In this study, our aim was to investigate the role of neurophysiological assessments of the occipital cortex in VS patients with (VSm ) or without migraine (VSwom ) and the healthy control (HC). METHODS: To assess the occipital cortex hyperexcitability, we conducted a prospective, observational study to investigate the habituation/potentiation response by repetitive pattern reversal visual evoked potentials (rVEP) and examined the phosphene thresholds (PT) by transcranial magnetic stimulation in VS patients with or without migraine who were admitted to our tertiary headache clinic and the healthy control. RESULTS: Twenty-nine volunteers were recruited. The VSm (n = 10), the VSwom (n = 7), and the HC group (n = 12) did not differ demographically. Flickering and floaters were reported in all VS patients and flickering in the dark was the most distressing symptomatology in both VS groups. Higher VAS scores for palinopsia (trailing), photophobia, and concentration difficulty were more frequently self-reported by VSm patients. The HC demonstrated habituation; however, there was loss of habituation response and decreased PTs in both groups of VS patients. The N1P1 VEP amplitude ratios of the 10th/1st block from right and left eye stimulation disclosed higher values (lack of habituation) in VSm (1.04 ± 0.2 and 1.06 ± 0.2) and the VSwom (1.05 ± 0.2 and 0.96 ± 0.08) patients compared to the healthy control (0.75 ± 0.1 and 0.79 ± 0.1), P = .002 from right eye and P = .003 from left eye. In the post hoc analysis the VS patients did not differ according to the presence of migraine from right or left eye stimulations (both P > .999). The left occipital cortex PTs were lower in VSm (58.00 ± 6.60) and VSwom (62.14 ± 11.53) and higher in the HC (71.33 ± 5.56) P = .009. In the post hoc analysis the VS patients did not differ according to the presence of migraine (P > .999). The right occipital cortex PTs were lower in VSm (60.30 ± 8.15) and VSwom (62.00 ± 10.95), higher in the HC (69.67 ± 8.04); however, statistically, groups did not differ (P = .087). CONCLUSIONS: The loss of habituation and lower threshold for occipital cortex excitability were demonstrated electrophysiologically in VS patients. While statistically significant loss of habituation was seen in both VS patients (with or without migraine) in the right eye, statistically significant loss of habituation in the left eye and decreased threshold of left occipital cortex excitability was seen in visual snow with migraine patients. These findings may provide new insights on "visual snow" pathophysiology and serve as an objective and quantitative assessment tool in VS patients.

Focal activation of neuronal circuits induced by microstimulation in the visual cortex.

OBJECTIVE: Microstimulation to the cortical tissue applied with penetrating electrodes delivers current that spreads concentrically around the electrode tip and is known to evoke focal visual sensations, i.e. phosphenes. However, to date, there is no direct evidence depicting the spatiotemporal properties of neuronal activity induced immediately after microstimulation and how such activity drives the subsequent local cortical circuits. APPROACH: In the present study, we imaged the spatiotemporal distribution of action potentials (APs) directly induced by microstimulation and the subsequent trans-synaptic signal propagation using a voltage-sensitive dye (VSD) and a calcium-sensitive dye (CaSD) in slice preparations of the mouse primary visual cortex. MAIN RESULTS: The directly induced APs were confined to the close vicinity of the electrode tip, and the effective distance of excitation was proportional to the square root of the current intensity. The excitation around the electrode tip in layer IV mainly propagated to layer II/III to further induce the subsequent focal activation in downstream local cortical circuits. The extent of activation in the downstream circuits was restrained by competitive interactions between excitatory and inhibitory signals. Namely, the spread of the excitation to lateral neighbor neurons along the layer II/III was confined by the delayed inhibition that also spread laterally at a faster rate. SIGNIFICANCE: These observations indicate that dynamic interactions between excitatory and inhibitory signals play a critical role in the focal activation of a cortical circuit in response to intracortical microstimulation and, therefore, in evoking a localized phosphene.