Microstimulation of V1 delays visually guided saccades: a parametric evaluation of delay fields

Electrical microstimulation of macaque striate cortex (area V1) delays the execution of saccadic eye movements made to a visual target placed in the receptive field of the stimulated neurons. The region of visual space within which saccades are delayed is called a delay field. We examined the effects of changing the parameters of stimulation and target size on the size of a delay field. Rhesus monkeys were required to generate a saccadic eye movement to a punctate and white visual target presented within or outside the receptive field of the neurons under study. On 50% of trials, a train of stimulation consisting of 0.2-ms anode-first pulses was delivered to the neurons before the onset of the visual target. Stimulations were performed in the operculum at 0.9–2.0 mm below the cortical surface. It was found that increases in current (50–100 μA), pulse frequency (100–300 Hz), or train duration (75–300 ms) increased the size of a delay field and increases in target size (0.1°–0.2° of visual angle) decreased the size of a delay field. Delay fields varied in size between 0.1 and 0.6° of visual angle. These results are related to the properties of phosphenes induced by electrical stimulation of V1 in humans and compared to the interference effects observed following transcranial magnetic stimulation of human V1.     

Stronger occipital cortical activation to lower than upper visual field stimuli Neuromagnetic recordings

 We recorded whole-scalp magnetoencephalographic (MEG) responses to black-and-white checkerboards to study whether the human cortical responses are quantitatively similar to stimulation of the lower and upper visual field at small, 0–6°, eccentricities. All stimuli evoked strongoccipital responses peaking at 50–100 ms (mean 75 ms). The activation was modeled with a single equivalent current dipole in the contralateral occipital cortex, close to the calcarine fissure, agreeing with an activation of the V1/V2 cortex. The dipole was, on average, twice as strong to lower than to upper field stimuli. Responses to hemifield stimuli that extended to both lower and upper fields resembled the responses to lower field stimuli in source current direction and strength. These results agree with psychophysical data, which indicate lower visual field advantage in complex visual processing. Parieto-occipital responses in the putative V6 complex were similar to lower and upper field stimuli. Received: 16 March 1998 / Accepted: 9 September 1998     

Transcranial magnetic stimulation in the visual system. II. Characterization of induced phosphenes and scotomas

Transcranial magnetic stimulation (TMS) induces phosphenes and disrupts visual perception when applied over the occipital pole. Both the underlying mechanisms and the brain structures involved are still unclear. In the first part of this study we show that the masking effect of TMS differs to masking by light in terms of the psychometric function. Here we investigate the emergence of phosphenes in relation to perimetric measurements. The coil positions were measured with a stereotactic positioning device, and stimulation sites were characterized in four subjects on the basis of individual retinotopic maps measured by with functional magnetic resonance imaging. Phosphene thresholds were found to lie a factor of 0.59 below the stimulation intensities required to induce visual masking. They covered the segments in the visual field where visual suppression occurred with higher stimulation intensity. Both phosphenes and transient scotomas were found in the lower visual field in the quadrant contralateral to the stimulated hemisphere. They could be evoked from a large area over the occipital pole. Phosphene contours and texture remained quite stable with different coil positions over one hemisphere and did not change with the retinotopy of the different visual areas on which the coil was focused. They cannot be related exclusively to a certain functionally defined visual area. It is most likely that both the optic radiation close to its termination in the dorsal parts of V1 and back-projecting fibers from V2 and V3 back to V1 generate phosphenes and scotomas.     

Abnormal functional connectivity between ipsilesional V5/MT+ and contralesional striate cortex (V1) in blindsight

Damage to the visual cortex can lead to changes in anatomical connectivity between the remaining areas. For example, after a unilateral lesion to striate cortex (V1), an abnormal anatomical pathway can develop between the lateral geniculate nucleus of the undamaged hemisphere and the motion area V5/MT+ in the damaged hemisphere, accompanied by a hypernormal callosal connection between the area V5/MT+ of the two hemispheres. Here we investigated, using transcranial magnetic stimulation (TMS), the functional significance of these pathways in the blindsight subject GY, in whom they were first demonstrated. We show that TMS applied over the extrastriate area V5/MT+ in GY’s damaged hemisphere modulates the appearance of phosphenes induced from V1 in the normal hemisphere. In contrast, in neurologically normal control subjects, TMS applied over V5/MT+ never influenced the phosphenes induced from V1 in the other hemisphere. The findings indicate an abnormal functional connectivity between V5/MT in the damaged hemisphere and the early visual cortex in the normal hemisphere, consistent with GY’s abnormal anatomical connectivity.     

Auditory evoked visual awareness following sudden ocular blindness: an EEG and TMS investigation

Neurophysiological and neuroanatomical studies have provoked controversy about whether the visual cortex may be more modifiable than previously believed. Auditory processing is enhanced in blind compared to sighted people, and the enhancement might reflect encroachment of auditory transmission onto visual cortex. To address this issue, we recorded the auditory event-related potentials (ERPs) correlated with auditory related paradoxical visual awareness in a subject with traumatic total late-onset blindness. We found that (1) there was auditory related brain activity over the occipital visual scalp regions starting from a very early stage (< 80 ms) and (2) this occipital activity was significantly different between “visually aware” and “visually unaware” responses in the P1 (40–80 ms) component following meaningful stimuli. There was also a significant difference between responses with and without visual awareness in the N1 (100–120 ms) component following either tones or meaningful stimuli. The phosphenes accompanying auditory stimuli in the ERP experiment were always perceived to be directly in front of the subject and this was reproduced by transcranial magnetic stimulation over the blind primary visual cortex and by sudden sounds delivered to the side or behind the subject. The TMS induced phosphenes were restricted to the central part of the space and were, at least qualitatively, the same as those induced by sounds. The results are clear evidence that human perceptual functions can be reorganized after sudden, late-onset, total ocular blindness.     

Repetitive common peroneal nerve stimulation increases ankle dorsiflexor motor evoked potentials in incomplete spinal cord lesions

Plasticity of corticospinal tract (CST) activity likely plays a key role in motor function recovery after central nervous system (CNS) lesions. In non-injured adults, 30 min of repetitive common peroneal nerve stimulation (rCPnS) increases CST excitability by 40–50% and the effect persists for at least 30 min. The present study evaluated with transcranial magnetic stimulation (TMS) the changes in CST excitability after 30 min of rCPnS in people with foot drop due to incomplete SCI. Suprathreshold rCPnS (25 Hz, alternating 1 s on 1 s off stimulation cycle) was given for two 15-min periods, while the subject sat at rest with ankle and knee joints fixed. Before, between, and after the periods of stimulation, the tibialis anterior (TA) motor evoked potentials (MEPs) to TMS were measured at a TMS intensity that originally produced a half-maximum MEP (typically 10–20% above threshold) while the sitting subject provided 25–30% maximum voluntary TA contraction. In 10 subjects with SCI, the peak-to-peak TA MEP increased by 14 ± 3% after rCPnS and the peak increase (+21 ± 7%) occurred 15 min after the cessation of rCPnS. The TA H-reflex, measured in separate experiments in 7 subjects, did not increase after rCPnS. The results indicate that rCPnS can increase CST excitability for the TA in people with incomplete SCI, although its effects appear smaller and shorter lasting than those found in non-injured control subjects. Such short-term plasticity in the CST excitability induced by rCPnS may contribute to long-term therapeutic effects of functional electrical stimulation previously reported in people with CNS lesions.     

Low frequency transcranial magnetic stimulation on the posterior parietal cortex induces visuotopically specific neglect-like syndrome

The visuo-parietal (VP) region of the cerebral cortex is critically involved in the generation of orienting responses towards visual stimuli. In this study we use repetitive transcranial magnetic stimulation (rTMS) to unilaterally and non-invasively deactivate the VP cortex during a simple spatial visual detection task tested in real space. Adult cats were intensively trained over 4 months on a task requiring them to detect and orient to a peripheral punctuate static LED presented at a peripheral location between 0° and 90°, to the right or left of a 0° fixation target. In 16 different interleaved sessions, real or sham low frequency (1 Hz) rTMS was unilaterally applied during 20 min (1,200 pulses) to the VP cortex. The percentage of mistakes detecting and orienting to contralateral visual targets increased significantly during the 15–20 min immediately following real but not sham rTMS. Behavioral deficits were most marked in peripheral eccentricities, whereas more central locations were largely unaffected. Performance returned to baseline (pre-TMS) levels when animals were tested 45 min later and remained in pre-TMS levels 24 h after the end of the stimulation. Our results confirm that the VP cortex of the cat is critical for successful detection and orienting to visual stimuli presented in the corresponding contralateral visual field. In addition, we show that rTMS disrupts a robust behavioral task known to depend on VP cortex and does so for the far periphery of the visual field, but not for more central targets.Prof. Payne passed away May 2004. This article is submitted in his memory.     

Modulation of visual cortical excitability in migraine with aura: effects of 1 Hz repetitive transcranial magnetic stimulation

Recent studies showed hyperexcitability of the occipital cortex in subjects affected by migraine with aura. It has been shown that 1 Hz repetitive transcranial magnetic stimulation (rTMS) reduces excitability of visual cortex in normal subjects. The aim of the study was to investigate the effects of low frequency (1 Hz) rTMS on visual cortical excitability by measuring changes in phosphene threshold (PT) in subjects with migraine with aura. Thirteen patients with migraine with aura and 15 healthy controls were examined. Using a standardized transcranial magnetic stimulation protocol of the occipital cortex, we assessed the PT (the lowest magnetic stimulation intensity at which subjects just perceived phosphenes) before and after a 1-Hz rTMS train delivered at PT intensity for 15 min. The difference in the proportion of subjects reporting phosphenes in migrainer and control groups was significant (migrainers: 100% vs controls 47%; P<0.05), and 1 Hz rTMS over the occipital cortex led to a significantly increased visual cortex excitability expressed as a decrease in PT in subjects affected by migraine with aura. Conversely, after a 1-Hz TMS train normal subjects showed increased PT values, which suggests a decreased visual cortex excitability. Our findings confirm that the visual cortex is hyperexcitable in migrainers and suggest a failure of inhibitory circuits, which are unable to be upregulated by low frequency rTMS.     

The effects of inverting prisms on the horizontal–vertical illusion: a systematic effect of downward gaze

The purpose of this work is to compare the relative contributions from the extraocular and sensory systems on the magnitude of the horizontal–vertical illusion (HVI). The visual HVI refers to the general tendency to overestimate vertical extensions of small-scale lines on a picture plane relative to the horizontal by 4–16% depending on the method of measurement. The HVI line stimuli consisted of luminous vertical and horizontal lines forming “L-profiles” located in the frontoparallel plane at a 45 cm viewing distance, collinearly with a binocular gaze. The home position of gaze was aligned to the center of the screen with the ear–eye angle concordant with the environmental horizontal. Illusion strength was quantified when subjects fixated the HVI line stimuli in four quadrants of the visual field. The HVI was also viewed through prism lenses that inverted the retinal images by 180°, thereby dissociating the sensory “up-down” direction from the oculomotor up-down frame of reference. The results revealed a systematically lower magnitude of the HVI in the bottom visual field regardless of whether subjects fixated the HVI with the distorting prisms or without. Taken together, these results suggest that the HVI is sensitive to small-angle gaze shifts. In agreement with several recent findings, these results are interpreted as implying that the brain imposes an enhanced analytic structure on the ascending sensory information during downward gaze. Hans O. Richter and Jaanus Raudsepp contributed equally to this work.     

Importance of attentional mechanisms in audiovisual links

 The effect of auditory cues at different levels of visual processing was examined by using a visual ”conjunction of features” discrimination task (experiment 1) and a ”feature” discrimination task (experiment 2). In both experiments the visual target, appearing either on the left or the right of Ss’ midline, was preceded by a brief tone either spatially proximal or distal to the target. In the ”conjunction” task, subjects had to discriminate the orientation of a T flanked with T distractors of different orientations. In this task, assumed to require focused attention, discrimination accuracy was increased when the sound cue occurred at the subsequent visual target location and was decreased when it occurred at its alternative location. In the ”feature” experiment, subjects had to discriminate the orientation of a line segment (±45°) presented among line segment distractors. Accuracy was not affected, either when the sound was proximal or when it was distal to the location of the visual target. Results suggest that the early processing of sensory information is modality specific and that interference of auditory stimulation with visual stimuli is more pronounced as the processing of visual stimuli requires focused attention. Received: 5 June 1998 / Accepted: 12 January 1999     

Influence of sensory deprivation and perturbation of trigeminal afferent fibers on corticomotor control of human tongue musculature

Several recent studies with transcranial magnetic stimulation (TMS) have demonstrated changes in motor evoked potentials (MEPs) in human limb muscles following modulation of sensory afferent inputs, but little is known about the regulation of the human tongue motor control. To test the effect of local anesthesia (LA) of the lingual nerve and topical application of capsaicin stimulation on tongue MEPs. Fourteen volunteers participated (21–30 years) in two randomized sessions; before, during a nerve block of the lingual nerve or topical capsaicin application (30 μl 5%) on the tongue, and after anesthesia or pain had subsided. EMG electrodes were placed on the tongue and the first dorsal interosseous (FDI) muscle (control). EMG signals were amplified, filtered (20 Hz–1 kHz), and sampled at 4 kHz (Nicolet, USA). TMS were delivered with a figure-of-eight coil (Magstim 200, UK). Scalp sites at which EMG responses were evoked in the relaxed tongue or FDI at the lowest stimulus strength were determined, i.e., motor threshold (T). MEPs were assessed using stimulus–response curves in steps of 10% T. Eight stimuli were presented at each stimulus level. The proximal hypoglossal nerve was activated by TMS delivered over the parieto-occipital skull distal to the right ear. Eight stimuli were delivered at 50% of maximum stimulator output. ANOVAs were used to analyze latency and peak-to-peak amplitudes. Capsaicin evoked mild pain (2.8±0.5), and a strong burning sensation (6.2±0.4) on 0–10 visual analogue scales. MEP amplitudes in tongue and FDI were not influenced by capsaicin (P>0.44) but by stimulus strength (P<0.001). MEP latencies in tongue (8.9±0.2 ms) and FDI (22.4±0.4 ms) were not affected by capsaicin (P>0.19). Hypoglossal nerve stimulation evoked a short-latency (3.6±0.9 ms) response (mean amplitude 65±9 μV); but was unaffected by capsaicin (P>0.54). LA did not have any effect on FDI MEPs but was associated with a significant facilitation of tongue MEPs at T+50% and T+60% about 50 min after the nerve block in the recovery phase. Also in this condition, the direct motor responses evoked by hypoglossal nerve stimulation remained constant. No direct effect of a strong burning sensation could be shown on peripheral or central corticomotor pathways to the relaxed tongue musculature, however, LA of the lingual nerve (cranial nerve V) seems able to induce a delayed change in corticomotor control of tongue musculature (cranial nerve XII) possibly related to unmasking effects at the cortical level but not completely excluding excitability changes at the brain stem level.     

Perceptual learning of line orientation modifies the effects of transcranial magnetic stimulation of visual cortex

Perceptual learning may be accompanied by physiological changes in early visual cortex. We used transcranial magnetic stimulation (TMS) to test the postulate that perceptual learning of a visual task initially performed at 60–65% accuracy strengthens visual processing in early visual cortex. Single pulse TMS was delivered to human occipital cortex at time delays of 70–154 ms after the onset of an odd-element, line orientation discrimination task. When TMS was delivered at a delay of 84 ms or later the accuracy of visual discrimination was transiently degraded in ten subjects. As visual performance in control trials without TMS improved with training, the absolute magnitude of TMS suppression of performance decreased in parallel. This result occurred both when TMS was delivered to broad areas of occipital cortex and when TMS was optimally delivered to early occipital cortex. No change in TMS suppression was observed when three new subjects were given feedback during an odd-element task that did not require substantial perceptual learning. Thus, perceptual learning improved visual performance and reduced TMS suppression of early visual cortex in parallel.     

Task-dependent modulation of inhibitory actions within the primary motor cortex

 In 11 healthy subjects motor-evoked potentials (MEPs) and silent periods (SPs) were measured in the right first dorsal interosseus (FDI) and abductor pollicis brevis muscles (APB): (1) when transcranial magnetic cortex stimulation (TMS) was applied at tonic isometric contraction of 20% of maximum force, (2) when TMS was applied during tactile exploration of a small object in the hand, (3) when TMS was applied during visually guided goal-directed isometric ramp and hold finger flexion movements, and (4) when at tonic isometric contraction peripheral electrical stimulation (PES) of the median nerve was delivered at various intervals between PES and TMS. Of the natural motor tasks, duration of SPs of small hand muscles was longest during tactile exploration (APB 205±42 ms; FDI 213±47 ms). SP duration at tonic isometric contraction amounted to 172±35 ms in APB and 178±31 ms in FDI, respectively. SP duration in FDI was shortest when elicited during visually guided isometric finger movements (159±15 ms). At tonic isometric contraction, SP was shortened when PES was applied at latencies –30 to +70 ms in conjunction with TMS. The latter effect was most pronounced when PES was applied 20 ms before TMS. PES-induced effects increased with increasing stimulation strength up to a saturation level which appeared at the transition to painful stimulation strengths. Both isolated stimulation of muscle afferents and of low-threshold cutaneous afferents shortened SP duration. However, PES of the contralateral median nerve had no effect on SPs. Amplitudes of MEPs did not change significantly in any condition. Inhibitory control of motor output circuitries seems to be distinctly modulated by peripheral somatosensory and visual afferent information. We conclude that somatosensory information has privileged access to inhibitory interneuronal circuits within the primary motor cortex. Received: 24 November 1997 / Accepted: 11 August 1998     

Impairments in the initial horizontal vestibulo-ocular reflex of older humans

To determine age-related changes, the initial horizontal vestibulo-ocular reflex (VOR) of 11 younger normal subjects (aged 20–32 years) was compared with that of 12 older subjects (aged 58–69 years) in response to random transients of whole-body acceleration of 1,000 and 2,800°/s² delivered around eccentric vertical axes ranging from 10 cm anterior to 20 cm posterior to the eyes. Eye and head positions were sampled at 1,200 Hz using magnetic search coils. Subjects fixed targets 500 cm or 15 cm distant immediately before the unpredictable onset of rotation in darkness. For all testing conditions, younger subjects exhibited compensatory VOR slow phases with early gain (eye velocity/head velocity, interval 35–45 ms from onset of rotation) of 0.90±0.02 (mean ± SEM) for the higher head acceleration, and 0.79±0.02 for the lower acceleration. Older subjects had significantly (P<0.0001) lower early gain of 0.77±0.04 for the higher head acceleration and 0.70±0.02 for the lower acceleration. Late gain (125–135 ms from onset of rotation) was similar for the higher and lower head accelerations in younger subjects. Older subjects had significantly lower late gain at the higher head acceleration, but gain similar to the younger subjects at the lower acceleration. All younger subjects maintained slow-phase VOR eye velocity to values ≥200°/s throughout the 250-ms rotation, but, after an average of 120 ms rotation (mean eccentricity 13°), 8 older subjects consistently had abrupt declines (ADs) in slow-phase VOR velocity to 0°/s or even the anticompensatory direction. These ADs were failures of the VOR slow phase rather than saccades and were more frequent with the near target at the higher acceleration. Slow-phase latencies were 14.4±0.4 ms and 16.8±0.4 ms for older subjects at the higher and lower accelerations, significantly longer than comparable latencies of 10.0±0.5 ms and 12.0±0.6 ms for younger subjects. Late VOR gain modulation with target distance was significantly attenuated in older subjects only for the higher head acceleration. Electronic Publication     

The assessment of position of stationary targets perceived during saccadic eye movement

Summary The experiment was performed to establish the accuracy with which visual targets perceived during saccadic eye movement are localised. Subjects were presented with the task of executing saccades of 30° plus amplitude, passing through primary gaze, about the time of peak velocity a 5 ms red flash was presented at some random position (up to 30° left or right of centre) on a horizontal visual display. Subjects were required to indicate the direction in which they thought the flash was localised by fixating in that direction. Observations were made under conditions of prolonged total darkness and in the presence of a contrasting background. Measurement was made of saccade velocity and eye displacement as an index of target positions. Eye displacement was linearly scaled with respect to true target direction. Targets were localised with an average error of 5°–6° although the variance was high. No systematic differences were found between conditions or subjects. Error was unrelated to saccade velocity. It is concluded that during saccadic eye movements the appreciation of target position is maintained with an acceptable degree of accuracy.     

Impairment of visual perception and visual short term memory scanning by transcranial magnetic stimulation of occipital cortex

Summary Transcranial magnetic stimulation (TMS) of occipital cortex was performed using a magneto-electric stimulator with a maximum output of 2 Tesla in 24 normal volunteers. The identification of trigrams, presented for 14 ms in horizontal or vertical arrays was significantly impaired when the visual stimulus preceded the occipital magnetic shock by 40 to 120 ms. The extent of impairment was related to TMS intensity. The latency of perceptual impairment was shorter for more intense TMS. No perceptual impairment was obtained by sham stimulation when TMS shocks were applied to the upper cervical region rather than the occipital region to rule out unspecific startle reactions affecting attention possibly responsible for the observed reduction in performance. Occipital TMS did not evoke systematic eye movements except for blink responses at latencies beyond 40 ms which were too late to interfere with visual input. Depending on the required serial order of readout of the trigram perceptual impairment was more marked for the second and third part of the trigram. This demonstrates that TMS interferes with the internal serial processing of visual input. To elucidate this further, TMS was used in a Sternberg short term visual memory scanning task. TMS caused a marked decrease in memory scanning rates whereas visual stimulus encoding and storage remained unaffected when tested at various TMS delays. TMS appears to be a useful method to study processes of visual perception and short term memory handling in the occipital cortex. Advantages over classical visual masking techniques especially regarding topical localisation are discussed.This work was partially supported by a grant from the Deutsche Forschungs Gemeinschaft (SFB 200/B9) to V.H.     

Interaction of paired cortical and peripheral nerve stimulation on human motor neurons

This paper contrasts responses in the soleus muscle of normal human subjects to two major inputs: the tibial nerve (TN) and the corticospinal tract. Paired transcranial magnetic stimulation (TMS) of the motor cortex at intervals of 10–25 ms strongly facilitated the motor evoked potential (MEP) produced by the second stimulus. In contrast, paired TN stimulation produced a depression of the reflex response to the second stimulus. Direct activation of the pyramidal tract did not facilitate a second response, suggesting that the MEP facilitation observed using paired TMS occurred in the cortex. A TN stimulus also depressed a subsequent MEP. Since the TN stimulus depressed both inputs, the mechanism is probably post-synaptic, such as afterhyperpolarization of motor neurons. Presynaptic mechanisms, such as homosynaptic depression, would only affect the pathway used as a conditioning stimulus. When TN and TMS pulses were paired, the largest facilitation occurred when TMS preceded TN by about 5 ms, which is optimal for summation of the two pathways at the level of the spinal motor neurons. A later, smaller facilitation occurred when a single TN stimulus preceded TMS by 50–60 ms, an interval that allows enough time for the sensory afferent input to reach the sensory cortex and be relayed to the motor cortex. Other work indicates that repetitively pairing nerve stimuli and TMS at these intervals, known as paired associative stimulation, produces long-term increases in the MEP and may be useful in strengthening residual pathways after damage to the central nervous system.     

Frequency-Following and Connectivity of Different Visual Areas in Response to Contrast-Reversal Stimulation

The sensitivity of visual areas to different temporal frequencies, as well as the functional connections between these areas, was examined using magnetoencephalography (MEG). Alternating circular sinusoids (0, 3.1, 8.7 and 14 Hz) were presented to foveal and peripheral locations in the visual field to target ventral and dorsal stream structures, respectively. It was hypothesized that higher temporal frequencies would preferentially activate dorsal stream structures. To determine the effect of frequency on the cortical response we analyzed the late time interval (220–770 ms) using a multi-dipole spatio-temporal analysis approach to provide source locations and timecourses for each condition. As an exploratory aspect, we performed cross-correlation analysis on the source timecourses to determine which sources responded similarly within conditions. Contrary to predictions, dorsal stream areas were not activated more frequently during high temporal frequency stimulation. However, across cortical sources the frequency-following response showed a difference, with significantly higher power at the second harmonic for the 3.1 and 8.7 Hz stimulation and at the first and second harmonics for the 14 Hz stimulation with this pattern seen robustly in area V1. Cross-correlations of the source timecourses showed that both low- and high-order visual areas, including dorsal and ventral stream areas, were significantly correlated in the late time interval. The results imply that frequency information is transferred to higher-order visual areas without translation. Despite the less complex waveforms seen in the late interval of time, the cross-correlation results show that visual, temporal and parietal cortical areas are intricately involved in late-interval visual processing.     

Interhemispheric transfer of phosphenes generated by occipital versus parietal transcranial magnetic stimulation

Phosphenes represent a perceptual effect of transcranial magnetic stimulation (TMS) or electric stimulation of visual cortical areas. One likely neural basis for the generation of static phosphenes is the primary visual cortex (V1) although evidence is controversial. A peculiar feature of V1 is that it has sparse callosal connections with the exception of a central portion of visual field representation. In contrast, visually responsive cortical areas in the parietal lobe have widespread callosal connections. Thus, interhemispheric transfer (IT) time of off-centre phosphenes should be slower when generated by V1 than by visual parietal areas. To verify this possibility, in Exp. 1 we measured IT of phosphenes generated by TMS applied to V1 and in Exp. 2 we measured IT of phosphenes obtained by TMS applied to posterior parietal cortex. In both experiments, we obtained static bright circular phosphenes appearing in the contralateral hemifield. We measured IT time behaviorally by comparing unimanual simple reaction time to the onset of a phosphene under crossed or uncrossed hemifield-hand condition (Poffenberger paradigm). In keeping with our prediction, we found a substantially longer IT time for V1 than for parietal phosphenes. Additionally, an IT similar to that obtained with V1 stimulation was found when participants were asked to imagine the phosphenes previously experienced during TMS. In conclusion, the present results suggest that IT of phosphenes either generated by V1 TMS or imagined is subserved by slower callosal channels than those of real visual stimuli or parietal phosphenes.     

Perturbation of visuospatial attention by high-frequency offline rTMS

The contribution of different cortical regions to visuospatial attention can be probed with the help of perturbation techniques, such as transcranial magnetic stimulation (TMS). Repetitive TMS (rTMS) has also been suggested as a tool for the therapy of brain injuries, by adjusting the neural excitability of injured or intact brain regions. Low- and high-frequency rTMS have been shown to result in subsequent (offline) reductions or increases of local cortical excitability, respectively. Previous studies demonstrated that low-frequency (1 Hz) rTMS of posterior parietal cortex (PPC) produced significantly reduced detection of stimuli in the visual hemifield contralateral to the stimulation site, as well as increased ipsilateral detection. We here explored the functional impact of high-frequency (20 Hz) rTMS with an attention task similar to that of a previous low-frequency study (Hilgetag et al. in Nat Neurosci 4:953–957, 2001). Normal healthy subjects (N = 14) received high-frequency rTMS (20 Hz, 10 min, 50% stimulator output) over right or left PPC (coordinate points P4 or P3). After stimulation of the right PPC, detection of single visual stimuli in the contralateral hemifield was significantly impaired. Generally, rTMS of right and left PPC produced mirror-symmetric trends in reduced contralateral detection. These effects were still present after post-TMS sham stimulation (more than 20 min after the end of active rTMS). The results suggest that attentional function can be perturbed by high-frequency rTMS as well as by low-frequency rTMS, despite potential differences in the underlying neural mechanisms. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.