Phosphene Threshold Research Articles

Retinal vessel oximetry as a sensitive metabolic monitoring method for transcorneal electrical stimulation in retinitis pigmentosa

AbstractBackgroundTranscorneal electrical stimulation (TES; OkuStim®) is a novel therapy method for patients with retinitis pigmentosa (RP). With progression of RP, loss of photoreceptors leads to less oxygen consumption and lower demand in the inner retina. Retinal oximetry (RO) as a non‐invasive method to analyze oxygen saturation in retinal vessels promises to be a useful therapy monitoring tool. The aim of our study was to compare the RO parameters at baseline and following TES.MethodsA total of 43 eyes of 22 subjects (11♀ 11♂) suffering from RP were examined. Stimulation was performed for 30 minutes weekly at 200% of the individual phosphene threshold on both eyes. The oxygen saturation was examined at baseline (BL), 1 week and 6 months after TES stimulation with the oxygen saturation tool of the Retinal Vessel Analyser (IMEDOS Systems UG, Germany). The global oxygen saturations, within 1.0–1.5 optic disc diameters from the disc margin, in retinal arterioles (A‐SO2; %) and venules (V‐SO2; %) were estimated and their difference (A‐V SO2; %) was calculated. In addition, we evaluated the diameters in the corresponding arterioles (D‐A; μm) and venules (D‐V; μm). ANOVA‐based linear mixed‐effects models were calculated with SPSS®.ResultsSix months after TES the A‐SO2 showed a tendency to increase (from 96.48 ± 12.27% to 100.15 ± 5.56%, p = 0.09), while the V‐SO2 showed a slight decrease (from 61.61 ± 12.78% to 59.79 ± 11.15%, p = 0.48). The A‐V SO2, which represents the oxygen consumption of the retina, showed a significant increase from 34.87 ± 9.38% at BL to 41.36 ± 9.18% after 6 months (p = 0.02). TES had no influence on the D‐A and D‐V (p > 0.6).ConclusionThese data indicate that TES therapy in RP leads to an increased oxygen consumption of the retina. Thus, RO proves to serve as a sensitive monitoring method for TES therapy in RP patients.

Metabolic monitoring of transcorneal electrical stimulation in retinitis pigmentosa.

Transcorneal electrical stimulation (TES) is a novel treatment approach for patients with retinitis pigmentosa (RP). With progression of RP, loss of photoreceptors leads to less oxygen consumption and lower demand in the retina. Retinal oximetry (RO), as a non-invasive method to analyse oxygen saturation in retinal vessels, promises to be a useful therapy monitoring tool. The aim of our study was to observe changes in RO that would be attributed to therapeutic intervention. A total of 43 eyes of 22 subjects (11♀ 11♂) suffering from RP were examined at baseline, after the first stimulation, 1 week and 6 months after TES (OkuStim®). Stimulation was performed for 30 min weekly at 200% of the individual phosphene threshold, simultaneously on both eyes. The oxygen saturation was examined at baseline and following TES stimulation with the oxygen saturation tool of the Retinal Vessel Analyser (RVA; IMEDOS Systems UG, Jena, Germany). The global oxygen saturation parameters (in %), within 1.0-1.5 optic disc diameters from the disc margin, in retinal arterioles (A-SO2) and venules (V-SO2) were estimated and their difference (A-V SO2) was calculated. In addition, we evaluated the diameters (in μm) in the corresponding arterioles (D-A) and venules (D-V). ANOVA-based linear mixed-effects models were calculated with SPSS®. Six months after TES treatment, the mean A-SO2 increased (from 96.48 ± 12.27 to 100.15 ± 5.56%, p = 0.09), while the V-SO2 decreased (from 61.61 ± 12.78 to 59.79 ± 11.15%, p = 0.48). The A-V SO2, which represents the oxygen consumption of the retina, showed a statistically significant increase from 34.87 ± 9.38% at baseline to 41.36 ± 9.18% after 6 months (p = 0.02). TES had no influence on the D-A and D-V (p > 0.6). These data indicate that TES therapy in RP leads to an increased oxygen consumption of the retina. RO may thus serve as a sensitive monitoring method for TES therapy in RP.

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.

Separation effect of early visual cortex V1 under different crowding conditions: a transcranial magnetic stimulation study.

The visual crowding makes it difficult to identify the patterns in peripheral vision, but the neural mechanism for this phenomenon is still unclear because of different opinions. To study the separation effect of early visual cortex V1 under different crowding conditions, single-pulse transcranial magnetic stimulation (TMS) is applied within the right V1. The experimental design includes two factors: TMS intensity (10%, 65%, and 90% of the phosphene threshold) and crowding conditions (high and low). The accuracy results show that there is a strong interaction between crowding and TMS conditions. When the TMS intensity is 65% or 90% of the phosphene threshold, more crowding will be perceived under the high crowding condition, and less crowding under the low crowding condition. We concluded that the high and the low crowding conditions can be separated by TMS. These results support the assumption that the crowding is related to V1 and occurs in the visual coding phase.

P64-S Reduced phosphene prevalence in ALS despite normal threshold

Introduction Although ALS is one of the most common degenerative diseases of the motor neuron system, symptoms, and findings of the disease are not always restricted solely to the motor system. Certain clinical and electrophysiological findings observed in ALS patients imply some sensorial abnormalities. The aim of this study to investigate whether visual sensorial involvement occurs in ALS patients. For this, we investigated occipital cortex excitability with the phosphene threshold method. Method Twenty-one ALS patients and 16 healthy controls were included in the study. Visual cortex TMS was performed using a standard round coil. TMS was performed in a semi-dark room. Eyes of participants were closed with an eye mask. Coil was placed vertically to 7 cm above the inion. Right, and left occipital cortices were stimulated at the same session. Short interval intracortical inhibition (SICI) and resting motor threshold (RMT) were also studied as well as ALSFRS-R scores in patients. Results Phosphenes were elicited in 13 (81.2%) of controls, 9 (42.9%) of ALS patients (p = 0.041). Mean phosphene thresholds obtained with the occipital TMS was no difference between two groups (p > 0.05). No correlation was found between the phosphene threshold and ALSFRS-R scores, SICI, RMT (p > 0.05) Discussion Results of this study indicated a reduced prevalence of phosphene in connection with decreased occipital cortex excitability in ALS patients for the first time. This finding may indicate the loss of function of V1, V2/V3 or abnormal connectivity between V1 and V2/V3, regardless of clinical status or motor cortex excitability of the patients.

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

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. 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). 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. 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). 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.

Migraine-linked characteristics of transcranial magnetic stimulation-induced phosphenes.

Transcranial magnetic stimulation is used to explore visual cortex hyperexcitability in migraine. We hypothesized that the phosphene threshold in subjects suffering from migraines with and without aura would be lower than in controls, and this phenomenon could be linked to higher pain and disability levels. We also implied that subjects with lower phosphene threshold could see more phosphenes of different colors and shapes. Our primary objective was to compare the phosphene threshold between migraine without aura, migraine with aura, and control groups and investigate which factors contribute to different phosphene parameters in migraineurs. Secondary objectives were to compare color, shape, and number of phosphenes between groups and assess pain and disability level correlation with the phosphene characteristics. Phosphene threshold in migraine without aura, migraine with aura, and control groups were 68 ± 9.5% vs. 75 ± 12%, vs. 80 ± 11%, respectively. Other phosphene parameters (number, color and shape) did not differ between groups. Average pain level during the attack did not correlate with phosphene threshold significantly, though the non-significant trend for negative correlation of migraine disability assessment scale score and a phosphene threshold has been found the higher was migraine disability assessment scale value, the lower was phosphene threshold (β = -0.255; P = 0.139). Other variables: gender, age, migraine subtype, migraine duration and use of hormone contraceptives - were not related to the phosphene threshold value. Our study provides additional data on visual cortex hyperexcitability in migraineurs, regarding transcranial magnetic stimulation with a figure-of-eight coil. Visual cortex excitability might be linked to higher disability.

Where Are the fMRI Correlates of Phosphene Perception?

Pulses of transcranial magnetic stimulation (TMS) over occipital cortex can induce transient visual percepts called phosphenes. Phosphenes are an interesting stimulus for the study of the human visual system, constituting conscious percepts without visual inputs, elicited by neural activation beyond retinal and subcortical processing stages in the visual hierarchy. The same TMS pulses, applied at threshold intensity phosphene threshold (PT), will prompt phosphene reports on half of all trials (“P-yes”) but not on the other half (“P-no”). Contrasting brain activity (P-yes > P-no) can provide unique information on neural mechanisms underlying conscious percepts, as has been demonstrated by published EEG studies. Yet to our knowledge no articles reporting analogous contrasts with functional magnetic resonance imaging (fMRI) have been published. Since it seems unlikely that such studies have never been performed, this straightforward and technically feasible idea may have been explored in multiple failed, and unpublished, attempts. Here, we argue why such unsuccessful attempts, even small-scale, best be shared. We also report our own failed attempt to find phosphene-related activity in fMRI. Threshold phosphenes are weak percepts, and their detection subjective and difficult. If fMRI correlates of phosphenes are obtainable with this contrast, small-scale (‘pilot’) measurements may not be sufficiently powerful to detect them. At the same time, due to the challenges and costs involved in TMS-fMRI, attempts might not often get beyond the piloting stage. We propose that the only way out of this quandary is the communication and sharing of such unsuccessful attempts and associated data.

Modulating the excitability of the visual cortex using a stimulation priming paradigm

BackgroundTranscranial random noise stimulation (tRNS) can cause long term increase of corticospinal excitability when used to prime the motor cortex, before measuring the motor response in the hand muscles with TMS (Terney et al., 2008). In cognitive studies, tRNS has been used to improve visual attention and mathematical skills, an enhancement effect that might suggest sustained cortical plasticity changes (Cappelletti et al., 2013; Snowball et al., 2013). However, while the behavioral evidence of increased performance is becoming substantiated by empirical data, it still remains unclear whether tRNS over visual areas causes an increase in cortical excitability similar to what has been found in the motor cortex, and if that increase could be a potential physiological explanation for behavioral improvements found in visual tasks. Objective/hypothesisIn the present study, we aimed to investigate whether priming the visual cortex with tRNS leads to increased and sustained excitability as measured with visual phosphenes. MethodsWe measured phosphene thresholds (PTs) using an objective staircase method to quantify the magnitude of cortical excitability changes. Single-pulse TMS was used to elicit phosphenes before, immediately after, and every 10 min up to one hour after the end of 20 min tRNS, anodal tDCS (a-tDCS) or sham. ResultsResults showed that phosphene thresholds were significantly reduced up to 60 min post stimulation relative to baseline after tRNS, a behavioral marker of increased excitability of the visual cortex, while a-tDCS had no effect. This result is very similar in magnitude and duration to what has been found in the motor cortex. ConclusionsOur findings demonstrate promising potential of tRNS as a tool to increase and sustain cortical excitability to promote improvement of cognitive functions.

Coordinated neural, behavioral, and phenomenological changes in perceptual plasticity through overtraining of synesthetic associations

Synesthesia is associated with additional perceptual experiences, which are automatically and consistently triggered by specific inducing stimuli. Synesthesia is also accompanied by more general sensory and cortical changes, including enhanced modality-specific cortical excitability. Extensive cognitive training has been shown to generate synesthesia-like phenomenology but whether these experiences are accompanied by neurophysiological changes characteristic of synesthesia remains unknown. Addressing this question provides a unique opportunity to elucidate the neural basis of perceptual plasticity relevant to conscious experiences. Here we investigate whether extensive training of letter-color associations leads not only to synesthetic experiences, but also to changes in cortical excitability. We confirm that overtraining synesthetic associations results in synesthetic phenomenology. Stroop tasks further reveal synesthesia-like performance following training. Electroencephalography and transcranial magnetic stimulation show, respectively, enhanced visual evoked potentials (in response to untrained patterns) and lower phosphene thresholds, demonstrating specific cortical changes. An active (using letter-symbol training) and a passive control confirmed these results were due to letter-color training and not simply to repeated testing. Summarizing, we demonstrate specific cortical changes, following training-induced acquisition of synesthetic phenomenology that are characteristic of genuine synesthesia. Collectively, our data reveal dramatic plasticity in human visual perception, expressed through a coordinated set of behavioral, neurophysiological, and phenomenological changes.

11. Excessive inhibitory visuomotor connections in Parkinson’s disease with freezing of gait

Objectives Freezing of gait (FoG) is an invalidating symptom in patients with Parkinson’s disease (PD); it is defined as a brief, episodic absence or marked reduction of forward progression of the feet despite the intention to walk. The pathophysiology of this phenomenon remains obscure. Visual information are crucial for the initiation and control of movement, therefore an impairment of the visuomotor connections may underlie FoG. We used transcranial magnetic stimulation (TMS) to assess bilateral physiological connections (VMc) between primary visual (V1) and motor (M1) areas in PD with (PD + FoG) and without FoG (PD-FoG).We hypothesized that PD+FoG would show an abnormal response in M1. Methods Twelve PD+FoG were compared with 12 PD-FoG and 12 healthy subjects (HS) of similar age and sex. VMc was assessed bilaterally in resting participants by delivering a conditioning stimulus (CS) over the phosphene hotspot of V1 (intensity 90% phosphene threshold, PT) followed at two random interstimulus intervals (ISIs) (18 and 40 ms) by a test stimulus (TS) over left and right M1 to elicit a motor evoked potential (MEP) of ∼1 mV from the controlateral first dorsal interosseous (FDI). Results In HS, the VMc was reproducible with MEP suppression at ISI of 18 and 40 ms. Similar effects occurred in PD-FoG. PD+FoG behaved differently, since the inhibitory VMc was significantly enhanced in the right, non-dominant hemisphere. Conclusions PD+FoG had an excessive inhibitory response of the right M1 to inputs travelling from V1. Significance This may represent one core factor for the pathophysiology of FoG.

P 62 The effect of alternating current stimulation on individual alpha – A rebound phenomenon?

Background Non-invasive brain stimulation (NiBS), including transcranial alternating current stimulation (tACS), has shown impressive effects ranging from short changes in neural activity to long lasting recovery maximization following neural injury. Despite these encouraging results, little is known about the mechanism of action. TACS may be in danger of facing the challenges of large effect variability and poor result reproducibility. A better understanding of the underlying neurophysiological mechanisms of tACS” effects on neuronal oscillations should help address these issues. Hypotheses about these mechanisms include neuronal entrainment as well as rebound phenomena. Originally, we assumed a frequency peak shift towards stimulation frequency to occur after AC stimulation as a correlate for entrainment. Therefore, we investigated the alpha band peak before and after 10 Hz retinofugal tACS (rtACS) as well as before, during and after well-established photic driving. Methods To address this question, we stimulated 15 healthy subjects with rtACS at a frequency of 10 Hz while recording EEG. Prior to stimulation, we assessed electrode impedances and phosphene thresholds and recorded a resting state EEG. We applied rtACS in 6 blocks of 30 s stimulation. We assessed spectral alpha power as well as alpha peak frequency (individual alpha) over occipital electrodes during baseline and 30 s after stimulation and compared the two in a repeated-measure ANOVA. Results The alpha peak frequency changed by a mean 0.02 Hz (+/−0.04), not correlated with the distance of the baseline alpha peak to stimulation frequency. A greater change in alpha peak frequency did not correlate with an increase in alpha power. Similar results were found during and after photic driving (0.03 (+/−0.05)). Conclusions Surprisingly, we did not find the expected frequency peak shift. This provides an argument against entrainment and in favor of a rebound effect, which would explain stabilization and enhancement of an intrinsic frequency following a period of inhibition. Still, this does not explain behavioral changes associated with effects during rtACS or the phenomenon of photic driving. As neural oscillators share features of both harmonic and relaxation oscillators, the mechanism of action may be a combination of both effects, where short periods of entrainment are followed by a rebound-like recruitment of similar patterned oscillators.

Initial activation state, stimulation intensity and timing of stimulation interact in producing behavioral effects of TMS

Behavioral effects of transcranial magnetic stimulation (TMS) have been shown to depend on various factors, such as neural activation state, stimulation intensity, and timing of stimulation. Here we examined whether these factors interact, by applying TMS at either sub- or suprathreshold intensity (relative to phosphene threshold, PT) and at different time points during a state-dependent TMS paradigm. The state manipulation involved a behavioral task in which a visual prime (color grating) was followed by a target stimulus which could be either congruent, incongruent or partially congruent with the color and orientation of the prime. In Experiment 1, single-pulse TMS was applied over the early visual cortex (V1/V2) or Vertex (baseline) at the onset of the target stimulus – timing often used in state-dependent TMS studies. With both subthreshold and suprathreshold stimulation, TMS facilitated the detection of incongruent stimuli while not significantly affecting other stimulus types. In Experiment 2, TMS was applied at 100ms after target onset –a time window in which V1/V2 is responding to visual input. Only TMS applied at suprathreshold intensity facilitated the detection of incongruent stimuli, with no effect with subthreshold stimulation. The need for higher stimulation intensity is likely to reflect reduced susceptibility to TMS of neurons responding to visual stimulation. Furthermore, the finding that in Experiment 2 only suprathreshold TMS induced a behavioral facilitation on incongruent targets (whereas facilitations in the absence of priming have been reported with subthreshold TMS) indicates that priming, by reducing neural excitability to incongruent targets, shifts the facilitatory/inhibitory range of TMS effects.

O158 Excessive inhibitory visuomotor connections in parkinson’s disease with freezing of gait

Freezing of gait (FoG) is an invalidating symptom in patients with Parkinson’s disease (PD); it is defined as a brief, episodic absence or marked reduction of forward progression of the feet despite the intention to walk. The pathophysiology of this phenomenon remains obscure. Visual information are crucial for the initiation and control of movement, therefore an impairment of the visuomotor connections may underlie FoG. We used transcranial magnetic stimulation (TMS) to assess bilateral physiological connections (VMc) between primary visual (V1) and motor (M1) areas in PD with (PD + FoG) and without FoG (PD-FoG).We hypothesized that PD+FoG would show an abnormal response in M1. Twelve PD+FoG were compared with 12 PD-FoG and 12 healthy subjects (HS) of similar age and sex. VMc was assessed bilaterally in resting participants by delivering a conditioning stimulus (CS) over the phosphene hotspot of V1 (intensity 90% phosphene threshold, PT) followed at two random interstimulus intervals (ISIs) (18 and 40 ms) by a test stimulus (TS) over left and right M1 to elicit a motor evoked potential (MEP) of ∼1 mV from the controlateral first dorsal interosseous (FDI). In HS, the VMc was reproducible with MEP suppression at ISI of 18 and 40 ms. Similar effects occurred in PD-FoG. PD+FoG behaved differently, since the inhibitory VMc was significantly enhanced in the right, non-dominant hemisphere. PD+FoG had an excessive inhibitory response of the right M1 to inputs travelling from V1. This may represent one core factor for the pathophysiology of FoG.

Downregulation of early visual cortex excitability mediates oscillopsia suppression.

Objective:To identify in an observational study the neurophysiologic mechanisms that mediate adaptation to oscillopsia in patients with bilateral vestibular failure (BVF).Methods:We directly probe the hypothesis that adaptive changes that mediate oscillopsia suppression implicate the early visual-cortex (V1/V2). Accordingly, we investigated V1/V2 excitability using transcranial magnetic stimulation (TMS) in 12 avestibular patients and 12 healthy controls. Specifically, we assessed TMS-induced phosphene thresholds at baseline and cortical excitability changes while performing a visual motion adaptation paradigm during the following conditions: baseline measures (i.e., static), during visual motion (i.e., motion before adaptation), and during visual motion after 5 minutes of unidirectional visual motion adaptation (i.e., motion adapted).Results:Patients had significantly higher baseline phosphene thresholds, reflecting an underlying adaptive mechanism. Individual thresholds were correlated with oscillopsia symptom load. During the visual motion adaptation condition, no differences in excitability at baseline were observed, but during both the motion before adaptation and motion adapted conditions, we observed significantly attenuated cortical excitability in patients. Again, this attenuation in excitability was stronger in less symptomatic patients.Conclusions:Our findings provide neurophysiologic evidence that cortically mediated adaptive mechanisms in V1/V2 play a critical role in suppressing oscillopsia in patients with BVF.

Seeing in the dark: Phosphene thresholds with eyes open versus closed in the absence of visual inputs

BackgroundVoluntarily opening or closing our eyes results in fundamentally different input patterns and expectancies. Yet it remains unclear how our brains and visual systems adapt to these ocular states.Objective/Hypothesis: We here used transcranial magnetic stimulation (TMS) to probe the excitability of the human visual system with eyes open or closed, in the complete absence of visual inputs. MethodsCombining Bayesian staircase procedures with computer control of TMS pulse intensity allowed interleaved determination of phosphene thresholds (PT) in both conditions. We measured parieto-occipital EEG baseline activity in several stages to track oscillatory power in the alpha (8–12 Hz) frequency-band, which has previously been shown to be inversely related to phosphene perception. ResultsSince closing the eyes generally increases alpha power, one might have expected a decrease in excitability (higher PT). While we confirmed a rise in alpha power with eyes closed, visual excitability was actually increased (PT was lower) with eyes closed. ConclusionsThis suggests that, aside from oscillatory alpha power, additional neuronal mechanisms influence the excitability of early visual cortex. One of these may involve a more internally oriented mode of brain operation, engaged by closing the eyes. In this state, visual cortex may be more susceptible to top-down inputs, to facilitate for example multisensory integration or imagery/working memory, although alternative explanations remain possible.

P313 Reactivation of iconic memory in a priming task by transcranial magnetic stimulation (TMS)

Introduction Iconic memory represents the registration of visual information in a high-capacity but fast decaying visuo-sensory buffer. It has recently been shown that the primary visual cortex contributes to this memory function. Objectives In this TMS study, we investigated visual priming effects when TMS is applied over the primary visual cortex after prime presentation to see whether TMS could reactivate or “replay” the prime information stored in the sensory buffer. Methods Prime and probe maintained the same shape (square) but varied in colours of the same mean luminance, leading to congruent vs incongruent prime-probe conditions. Observers (n = 14) were asked to identify the colour of the probe as accurately and as fast as possible. Each trial started by a fixation cross lasting between 500–2000 ms. A prime was then flashed for 10 ms within the lower RVF at the location of TMS-induced phosphenes. A probe was displayed 400 ms after the prime for 40 ms at a mirrored location in the lower LVF. In TMS blocks, single-pulse TMS below phosphene thresholds was randomly delivered at 100 ms or 300 ms after the prime onset and intermingled with no TMS trials. Control trials (with no TMS) aiming at emulating a possible TMS-induced replay consisted of a physical redisplay of the prime at 300 ms i) in the same but faint colour, ii) in the opponent colour or iii) of a grey mask while responses to probes were recorded. The design was the same in SHAM blocks. Results Results showed that the significant priming effect (reaction times, RTs congruent Conclusion This is evidence that a memory trace stored in the sensory buffer in V1/V2 can be reactivated by TMS. The study is supported by a Wellcome Trust Award to Gregor Thut and Joachim Gross [grant number 098434, 098433] and by a Biological Sciences Research Council (BB /I006494/1) grant.

P184 Individual transcranial alternating current stimulation (tACS) within the beta range during verbal working memory

Introduction Beta band brain oscillations (13–30 Hz) correlate with cognitive manipulations during language processing ( Weiss and Muller, 2012 ). In particular, they are associated with the active maintenance of stimuli in verbal working memory ( Weiss and Rappelsberger, 2000 ). Therefore, beta oscillations are suited for tACS during verbal memory encoding. Objectives We examined whether 18 Hz tACS stimulation modulates verbal WM performance in a healthy participant. We did this single-case study since most tACS results are based on group studies and we want to test tACS in individual patients with disturbances of verbal WM. Materials & Methods A right-handed female (27 y) had to memorize 600 visually presented concrete words (150 nouns, 150 verbs; randomly presented two times) and do subsequent free recall. tACS in the beta (18 Hz) and alpha (9 Hz) band as well as a sham stimulation was applied in a double-blind multiple treatment design (ABCBCA) on 6 different days with at least 24 h between sessions. tACS-intensity was 350 μA (below individual phosphene and discomfort threshold). 20 min stimulation was applied at left temporo-parietal and right fronto-central sites. Results A significant difference between the stimulation and sham condition (Pearson χ2 = 12.0, p = 0.03, two-tailed) was found which differed for nouns and verbs. During beta stimulation the participant showed a 48% increase of recalled nouns (8% for verbs), during alpha stimulation a 28% (26 % for verbs) and during sham a 20% (36% for verbs) increase. Overall error rate was higher for verbs (Pearson χ2 = 11.73, p = 0.008, two-tailed). The influence of beta vs. alpha stimulation could not be reliably distinguished with the current protocol. Conclusion Although, beta oscillations are important for linking past and present input into a coherent representation of memorized contents ( Weiss and Rappelsberger, 2000 , Kopell and Whittington, 2011 ), no significant difference was found between alpha and beta stimulation. The word category difference is in accordance with previous findings ( Fiori and Cipollari, 2013 ) who revealed better performance for verb versus noun processing when stimulating left frontal in contrast to temporal areas.

P189 Transcranial modulation of visually induced gamma power: a concurrent TACS-MEG study

Introduction Alpha oscillations (8–12 Hz) are proposed to mediate ‘attentional gating’ by suppressing neuronal processing in task-irrelevant sensory regions, reflected by ‘pulsed-inhibition’ of stimulus-induced gamma-band activity (40–100 Hz). Concurrent TACS-MEG has the potential to reveal TACS entrainment of alpha oscillations at the stimulation site and thus their causal impact on neuronal activity representing stimulus processing. Objectives We aimed to provide evidence that TACS can entrain the phase of alpha oscillations in the visual cortex by assessing its modulatory impact on the power of visual stimulus-induced gamma oscillations via simultaneous MEG recordings. Materials & methods TACS was applied during MEG in intermingled 5.4s trials either in Oz-Cz or FPz-Cz montage. Montage and stimulation frequency were randomized across trials, applying either individual alpha frequency (IAF), IAF−4 Hz, IAF+4 Hz, or no stimulation, resulting in a 2 (Montage) × 3 (Frequency) design plus a ‘NoStim’ condition. Stimulation intensity for both montages was adjusted separately to 95% retinal phosphene threshold. Participants performed a simple visual detection task, attending an inward moving grating, known to induce strong occipital gamma responses. TACS artifacts were reduced via regression methods, LCMV beamformer time-course extraction from the visual cortex, and high-pass filtering. Importantly, the gamma frequency of interest (∼50–60 Hz) was largely unaffected by TACS artifacts. We compared TACS-to-gamma phase-power coupling (PAC) for the respective experimental conditions. Results We found a rhythmic modulation of stimulus-induced gamma power by TACS at IAF (i.e., TACS-gamma phase-amplitude coupling) for the Oz-Cz montage, but not for the FPz-Cz montage which was introduced to control for subthreshold retinal entrainment effects. Conclusion Our findings (i) demonstrate that concurrent TACS-MEG can principally be used to study cross-frequency-coupling between transcranially entrained slower and spontaneous or stimulus-related faster oscillations, (ii) cannot merely result from subthreshold retinal entrainment, and (iii) suggest that alpha oscillations are indeed a possible means for top-down suppression of bottom-up sensory processing.

Reliability of TMS phosphene threshold estimation: Toward a standardized protocol

BackgroundPhosphenes induced by transcranial magnetic stimulation (TMS) are a subjectively described visual phenomenon employed in basic and clinical research as index of the excitability of retinotopically organized areas in the brain. ObjectivePhosphene threshold estimation is a preliminary step in many TMS experiments in visual cognition for setting the appropriate level of TMS doses; however, the lack of a direct comparison of the available methods for phosphene threshold estimation leaves unsolved the reliability of those methods in setting TMS doses. The present work aims at fulfilling this gap. MethodsWe compared the most common methods for phosphene threshold calculation, namely the Method of Constant Stimuli (MOCS), the Modified Binary Search (MOBS) and the Rapid Estimation of Phosphene Threshold (REPT). In two experiments we tested the reliability of PT estimation under each of the three methods, considering the day of administration, participants' expertise in phosphene perception and the sensitivity of each method to the initial values used for the threshold calculation. ResultsWe found that MOCS and REPT have comparable reliability when estimating phosphene thresholds, while MOBS estimations appear less stable. ConclusionsBased on our results, researchers and clinicians can estimate phosphene threshold according to MOCS or REPT equally reliably, depending on their specific investigation goals. We suggest several important factors for consideration when calculating phosphene thresholds and describe strategies to adopt in experimental procedures.