Transcranial magnetic stimulation in the visual system. I. The psychophysics of visual suppression

When applied over the occipital pole, transcranial magnetic stimulation (TMS) disrupts visual perception and induces phosphenes. Both the underlying mechanisms and the brain structures involved are still unclear. The first part of the study characterizes the suppressive effect of TMS by psychophysical methods. Luminance increment thresholds for orientation discrimination were determined in four subjects using an adaptive staircase procedure. Coil position was controlled with a stereotactic positioning device. Threshold values were modulated by TMS, reaching a maximum effect at a stimulus onset asynchrony (SOA) of approx. 100 ms after visual target presentation. Stronger TMS pulses increased the maximum threshold while decreasing the SOA producing the maximum effect. Slopes of the psychometric function were flattened with TMS masking by a factor of 2, compared to control experiments in the absence of TMS. No change in steepness was observed in experiments using a light flash as the mask instead of TMS. Together with the finding that at higher TMS intensities, threshold elevation occurs even with shorter SOAs, this suggests lasting inhibitory processes as masking mechanisms, contradicting the assumption that the phosphene as excitatory equivalent causes masking. In the companion contribution to this one we present perimetric measurements and phosphene forms as a function of the stimulation site in the brain and discuss the putative generator structures.     

Topography of occipital EEG-reduction upon visual stimulation

Summary Visual stimuli were designed to drive a high proportion of the neurons in restricted parts of the human visual cortex. These stimuli were used to examine changes in the ongoing EEG during visual stimulation. The topographic organization of these changes was studied. It was found that the EEG from those parts of the cortex that are exposed to the stimulus is strongly reduced in amplitude. This stimulus dependency is indicative that cortical processing results itself in a reduction of the ongoing EEG, presumably due to desynchronization of neurons. The method shows that ongoing EEG can be used for functional mapping of cortical areas and is therefore valuable in situations where stimulus locked activity can not be measured.     

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.     

Variability comparison of simultaneous brain near-infrared spectroscopy and functional magnetic resonance imaging during visual stimulation

Brain near-infrared spectroscopy (NIRS) is emerging as a potential alternative to functional magnetic resonance imaging (fMRI). To date, no study has explicitly compared the two techniques in terms of measurement variability, a key parameter dictating attainable statistical power. Here, NIRS and fMRI were simultaneously recorded during event-related visual stimulation. Inter-subject coefficients of variation (CVs) for peak response amplitude were considerably larger for NIRS than fMRI, but inter-subject CVs for response latency and intra-subject CVs for response amplitude were overall comparable. Our results may represent an optimistic estimate of the CVs of NIRS measurements, as optode positioning was guided by structural MRI, which is normally unavailable. We concluded that fMRI may be preferable to NIRS for group comparisons, but NIRS is equally powerful when comparing conditions within participants. The discrepancy between inter- and intra-subject CVs is likely related to variability in head anatomy and tissue properties, which may be better accounted for by emerging NIRS technology.     

Transient visual field defects induced by transcranial magnetic stimulation over human occipital pole

Transient visual field defects (VFDs) and phosphenes were induced in normal volunteers by means of transcranial magnetic stimulation (TMS) using a circular magnetic coil of 12.5 cm diameter placed with its lower rim 2–4 cm above the inion in the midline. Subjects had to detect small, bright dots presented randomly for 14 ms in one of 60 locations on a computer screen resulting in a plot of the central 9° of the visual field. In 8 of 17 subjects, transient VFDs were inducible at peak magnetic field strenghts of 1.1–1.4 T. In the central 1–3°, detection of targets was impaired in both the upper and lower visual field, whereas at 4–9° large parts of only the lower visual field were affected with a sharp cut-off along the horizontal meridian. Targets at 1° in the lower field were affected with lower TMS intensities than corresponding locations in the upper or peripheral locations in the lower field. Detection of central targets was affected at more caudal stimulation sites than detection of peripheral targets. Phosphenes were elicitable in 14 of 17 subjects at clearly lower field strengths of 0.6–1.0 T. Many subjects perceived chromatophosphenes. From a discussion of the literature on patients with VFDs and the known topography of the human visual system, it is concluded that the transient VFDs at 1–3° are probably due to stimulation of both striate cortex (V1) and extrastriate areas (V2/V3), while VFDs in the lower visual field at eccentricities 4–9° are due to stimulation of V2/V3 but not V1. Received: 14 January 1997 / Accepted: 2 June 1997     

Localizing the site of magnetic brain stimulation by functional MRI

In order to locate the site of action of transcranial magnetic stimulation (TMS) within the human motor cortices, we investigated how the optimal positions for evoking motor responses over the scalp corresponded to the hand and leg primary-motor areas. TMS was delivered with a figure-8 shaped coil over each point of a grid system constructed on the skull surface, each separated by 1 cm, to find the optimal site for obtaining motor-evoked potentials (MEPs) in the contralateral first dorsal interosseous (FDI) and tibialis anterior (TA) muscles. Magnetic resonance imaging scans of the brain were taken for each subject with markers placed over these sites, the positions of which were projected onto the cortical region just beneath. On the other hand, cortical areas where blood flow increased during finger tapping or leg movements were identified on functional magnetic resonance images (fMRI), which should include the hand and leg primary-motor areas. The optimal location for eliciting MEPs in FDI, regardless of their latency, lay just above the bank of the precentral gyrus, which coincided with the activated region during finger tapping in fMRI studies. The direction of induced current preferentially eliciting MEPs with the shortest latency in each subject was nearly perpendicular to the course of the precentral gyrus at this position. The optimal site for evoking motor responses in TA was also located just above the activated area during leg movements identified within the anterior portion of the paracentral lobule. The results suggest that, for magnetic stimulation, activation occurs in the primary hand and leg motor area (Brodmann area 4), which is closest in distance to the optimal scalp position for evoking motor responses. Received: 18 February 1997 / Accepted: 26 January 1998     

Development of retinofugal neuropil areas in the brain of the alpine newt, Triturus alpestris. II. Topographic organization and formation of projections

Summary The development of retinal projections and the formation of their retinotopic organization were studied by means of anterograde transport of horseradish peroxidase in the newt, Triturus alpestris. All tracts found in the adult on the contralateral brain side are established during embryonic stages. At this stage a few uncrossed fibers are also detectable. Retinal fibers project first to the contralateral optic tectum. These are followd by contralateral projections to thalamic recipient areas. Beginning at embryonic stages, the projections from the retinal quadrants into the optic tectum are topographically organized. The other terminal areas innervated by the marginal optic tract (MaOT) show a topographic order from midlarval stages. The terminal areas innervated by the medial optic tract (MeOT) show no clear topographic organization at any stage. The contralateral projection of the MeOT orginates from the central area of the retina, whereas the uncrossed projection originates from the temporal peripheral retina. Ipsilateral (uncrossed) retinal projections develop during metamorphic climax. The MeOT is more distinct than the MaOT. The latter shows a clear retinotopic organization. The topography of the ipsilateral MaOT and its corresponding terminal areas are mirror-symmetric to the contralateral tract and terminal areas.Abbreviations AOF Axial optic fascicle - BON Basal optic neuropil - BOT Basal optic tract - c Caudal - C CGT, corpus geniculatum thalamicum - d Dorsal - dg Dorsal retinal quadrant - m Medial - MgOT Marginal optic tract - Med Medulla oblongata - MeOT Medial optic tract - NBl Neuropil Bellonci pars lateralis - NBm Neuropil Bellonci pars medialis - ON Optic nerve - nq Nasal retinal quadrant - OT Optic tract - PTN, P Posterior thalamic neuropil - r Rostral - t Temporal - Tel Telencephalon - TO Optic tecrum - tq Temporal retinal quadrant - UF, U Uncinate field - v Ventral - vq Ventral retinal quadrant     

Transcranial magnetic stimulation and the motor learning-associated cortical plasticity

It has been well established that repetitive motor performance and skill learning alter the functional organization of human corticomotoneuronal system. Over the past decade, transcranial magnetic stimulation (TMS) has helped to demonstrate motor practice and learning-related changes in corticomotoneuronal excitability and representational plasticity. It has also provided some insights into the mechanisms underlying such plasticity. TMS-derived indices show that motor practice, skill acquisition and learning are associated with an increase in cortical excitability and a modulation of intracortical inhibition partly related to the amount of GABA-related inhibition. It has been suggested that these changes in excitability might be related to learning and motor memory formation in the motor cortex. However, it has proved difficult to relate different aspects of TMS-derived representational plasticity with specific behavioral outcomes. A better understanding of the relationship between TMS measurements of practice-related cortical plasticity and underlying mechanisms, in the context of associated changes in behavior, will facilitate the development of techniques and protocols that will allow predictable modulation of cortical plasticity in health and disease.     

Peripheral nerve stimulation by induced electric currents: Exposure to time-varying magnetic fields

The review evaluates thresholds of peripheral nerve stimulation by complex current waveforms. A neuroelectric model employing Frankenhaeuser-Huxley membrane nonlinearities is used to derive excitation thresholds for monophasic and biphasic pulse sequences, as well as sinusoidal stimuli. The model, along with principles of magnetic field induction, is used to derive criteria of acceptability for exposure to time-varying magnetic fields. Applications to pulsed gradient fields from magnetic resonance imaging devices are discussed.     

Transcranial magnetic stimulation to right parietal cortex modifies the attentional blink

The attentional blink (AB) reflects a limitation in the ability to identify multiple items in a stream of rapidly presented information. Repetitive transcranial magnetic stimulation (rTMS), applied to a site over the right posterior parietal cortex, reduced the magnitude of the AB to visual stimuli, whilst no effect of rTMS was found when stimulation took place at a control site. The data confirm that the posterior parietal cortex may play a critical role in temporal as well as spatial aspects of visual attention.     

Somatotopical relationships between cortical activity and reflex areas in reflexology: A functional magnetic resonance imaging study

We examined the somatotopical relationship between cortical activity and sensory stimulation of reflex areas in reflexology using functional magnetic resonance imaging. Three reflex areas on the left foot, relating to the eye, shoulder, and small intestine were stimulated during the experiment. A statistical analysis showed that reflexological stimulation of the foot reflex areas corresponding to the eye, shoulder, and small intestine activated not only the somatosensory areas corresponding to the foot, but also the somatosensory areas corresponding to the eye, shoulder, and small intestine or neighboring body parts. Thus, the findings showed that reflexological stimulation induced a somatosensory process corresponding to the stimulated reflex area and that a neuroimaging approach can be used to examine the basis of reflexology effects.     

多模态MRI技术结合神经导航术中超声在枕叶视觉功能区胶质瘤手术中的应用

目的 探讨多模态MRI技术结合神经导航及术中超声在大脑枕叶视觉功能区胶质瘤手术中的应用价值。方法 回顾性分析2012年1月—2014年11月安徽医科大学附属省立医院神经外科收治的20例大脑枕叶视觉功能区胶质瘤患者手术相关资料,其中男9例、女11例,年龄27~72岁,均行神经显微手术治疗。术前利用灌注加权成像、弥散张量成像及血氧水平依赖功能MRI多模态MRI技术结合神经导航进行图像融合,重建病灶与视皮层及视辐射的3D图像位置,设计合适的手术入路、界定病灶切除范围;术中超声实时判断肿瘤切除程度,合理保护功能区和视辐射。结果 根据术后复查MRI结果,影像学全切除85.0%(17/20),大部分切除15.0%(3/20)。术后随访1~30个月,肿瘤大部分切除3例分别于术后7、13、15个月复发;与术前相比,视力视野改善与术前相比,视力视野改善60%(12/20),无明显变化40%(8/20)。结论 多模态MRI技术结合神经导航及术中超声,能够准确定位枕叶视觉功能区和视辐射的走行,制定个体化手术方案,提高了枕叶视觉功能区胶质瘤外科治疗的安全性和有效性,实现最大程度保护脑功能的同时最大范围切除肿瘤组织,提高患者术后生存质量。     

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.     

电刺激与磁刺激运动诱发电位的比较研究

在２２名正常成人志愿者的上下肢比较电与磁两种经皮运动皮层、脊髓刺激法所引出之运动诱发电位（ＭＥＰ）的差异。结果表明，电刺激诱发成功率为１００％，磁刺激在下肢肌诱发成功率为０％～１４．３％（皮层刺激）和０％～４２．９％（脊髓刺激）；电刺激ＭＥＰ波幅比磁刺激高２．４７～４１倍（平均１１．３倍）；电刺激ＭＥＰ潜时比磁刺激平均短２．７８ｍｓ（皮层刺激）和１．３４ｍｓ（脊髓刺激）。作者认为，易引出高大而可靠的ＭＥＰ的电刺激方法值得临床推广应用，而磁刺激法则应加强基础和方法学研究。     

Transcranial magnetic stimulation of the human brain: responses in muscles supplied by cranial nerves

Summary The present investigation demonstrates that time-varying magnetic fields induced over the skull elicit distinct types of responses in muscles supplied by the cranial nerves both on the ipsilateral and the contralateral side. When the center of the copper coil was positioned 4 cm lateral to the vertex on a line from the vertex to the external auditory meatus, bilateral responses in the masseter, orbicularis oculi, mentalis, and sternocleidomastoideus muscles with a delay of about 10 to 14 ms after the stimulus occurred. Similar to the transcranially evoked muscle responses in hand muscles, the responses in the cranial muscles can be influenced in latency and amplitude by background excitation. It is concluded that these responses are induced by excitation of the face-associated motor cortex followed by multiple I-waves in the corticonuclear tract with both ipsilateral and contralateral projections to the corresponding motoneurones. Additionally, at higher stimulation strengths short-latency ipsilateral responses in muscles supplied by the trigeminal, facial, and accessory nerves occurred which we suggest are induced by direct stimulation of the peripheral cranial nerves in their intracisternal course. The present study confirms the bilateral projection of corticonuclear tracts in awake unanesthetised human subjects which has been observed by electrical stimulation on the exposed cortex during surgical procedures already decades ago. The present investigation will serve as a basis for the assessment of pathophysiological mechanisms involving the corticonuclear system or the peripheral cranial nerves in their proximal parts in awake humans.Supported by the Deutsche Forschungsgemeinschaft     

Modulation of phosphene perception during saccadic eye movements: a transcranial magnetic stimulation study of the human visual cortex

Saccadic suppression allows for perceptual stability during rapid movements of the eyes. One of the neural mechanisms may involve saccade-related modulation of neural activity in the visual cortex. Using the perception of phosphenes induced by transcranial magnetic stimulation (TMS) applied over the visual cortex (VC) as an index of cortical excitability, we sought to determine if VC excitability was modulated at varying times relative to saccade onset. We used two measures of excitability: (1) stimulator intensity required to induce phosphenes in 50% of trials, also called the phosphene threshold (PT), and (2) the subjective intensity of the phosphene. We found that there was no change in PT for different saccade-TMS onset asynchronies while there was an increase in perceived phosphene-intensity near the time of saccade onset (F(7,42)=4.34, P=0.001). Contrary to what would be expected from a saccadic suppression model, our results suggest that excitability of the visual cortex is slightly enhanced at the time of saccade onset.     

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.     

Striate cortex in humans demonstrates the relationship between activation and variations in visual form

Electrophysiologic and functional imaging studies have shown that the visual cortex produces differential responses to the presence or absence of structure within visual textures. To further define and characterize regions involved in the analysis of form, functional magnetic resonance imaging (fMRI) was used to detect changes in activation during the viewing of four levels of isodipole textures. The texture levels systematically differed in the density of visual features such as extended contours and blocks of solid color present within the images. A linear relationship between activation level and density of structure was observed in the striate cortex of human subjects. This finding suggests that a special subpopulation of striate cortical neurons participates in the ability to extract and process structural continuity within visual stimuli. Received: 8 July 1998 / Accepted: 25 May 1999     

Short-term reduction of intracortical inhibition in the human motor cortex induced by repetitive transcranial magnetic stimulation

Ten healthy subjects and two patients who had an electrode implanted into the cervical epidural space underwent repetitive transcranial magnetic stimulation (rTMS; 50 stimuli at 5 Hz at active motor threshold intensity) of the hand motor area. We evaluated intracortical inhibition before and after rTMS. In healthy subjects, we also evaluated threshold and amplitude of motor evoked potentials (MEPs), duration of cortical silent period and short-latency intracortical facilitation. rTMS led to a short-lasting reduction in the amount of intracortical inhibition in control subjects with a high interindividual variability. There was no significant effect on other measures of motor cortex excitability. Direct recordings of descending corticospinal volleys from the patients were consistent with the idea that the effect of rTMS on intracortical inhibition occurred at the cortical level. Since the level of intracortical inhibition can be influenced by drugs that act on GABAergic systems, this may mean that low-intensity repetitive magnetic stimulation at 5 Hz can selectively modify the excitability of GABAergic networks in the human motor cortex. Electronic Publication