Stephan A. Brandt

α-Band Electroencephalographic Activity over Occipital Cortex Indexes Visuospatial Attention Bias and Predicts Visual Target Detection

Covertly directing visual attention toward a spatial location in the absence of visual stimulation enhances future visual processing at the attended position. The neuronal correlates of these attention shifts involve modulation of neuronal “baseline” activity in early visual areas, presumably through top-down control from higher-order attentional systems. We used electroencephalography to study the largely unknown relationship between these neuronal modulations and behavioral outcome in an attention orienting paradigm. Covert visuospatial attention shifts to either a left or right peripheral position in the absence of visual stimulation resulted in differential modulations of oscillatory α-band (8–14 Hz) activity over left versus right posterior sites. These changes were driven by varying degrees of α-decreases being maximal contralateral to the attended position. When expressed as a lateralization index, these α-changes differed significantly between attention conditions, with negative values (α_right < α_left) indexing leftward and more positive values (α_left ≤ α_right) indexing rightward attention. Moreover, this index appeared deterministic for processing of forthcoming visual targets. Collapsed over trials, there was an advantage for left target processing in accordance with an overall negative bias in α-index values. Across trials, left targets were detected most rapidly when preceded by negative index values. Detection of right targets was fastest in trials with most positive values. Our data indicate that collateral modulations of posterior α-activity, the momentary bias of visuospatial attention, and imminent visual processing are linked. They suggest that the momentary direction of attention, predicting spatial biases in imminent visual processing, can be estimated from a lateralization index of posterior α-activity.

Spontaneous eye movements during visual imagery reflect the content of the visual scene

In nine nave subjects eye movements were recorded while subjects viewed and visualized four irregularly-checkered diagrams. Scanpaths, defined as repetitive sequences of fixations and saccades were found during visual imagery and viewing. Positions of fixations were distributed according to the spatial arrangement of subfeatures in the diagrams. For a particular imagined diagrammatic picture, eye movements were closely correlated with the eye movements recorded while viewing the same picture. Thus eye movements during imagery are not random but reflect the content of the visualized scene. The question is discussed whether scanpath eye movements play a significant functional role in the process of visual imagery.

Consensus paper: Combining transcranial stimulation with neuroimaging

In the last decade, combined transcranial magnetic stimulation (TMS)-neuroimaging studies have greatly stimulated research in the field of TMS and neuroimaging. Here, we review how TMS can be combined with various neuroimaging techniques to investigate human brain function. When applied during neuroimaging (online approach), TMS can be used to test how focal cortex stimulation acutely modifies the activity and connectivity in the stimulated neuronal circuits. TMS and neuroimaging can also be separated in time (offline approach). A conditioning session of repetitive TMS (rTMS) may be used to induce rapid reorganization in functional brain networks. The temporospatial patterns of TMS-induced reorganization can be subsequently mapped by using neuroimaging methods. Alternatively, neuroimaging may be performed first to localize brain areas that are involved in a given task. The temporospatial information obtained by neuroimaging can be used to define the optimal site and time point of stimulation in a subsequent experiment in which TMS is used to probe the functional contribution of the stimulated area to a specific task. In this review, we first address some general methodologic issues that need to be taken into account when using TMS in the context of neuroimaging. We then discuss the use of specific brain mapping techniques in conjunction with TMS. We emphasize that the various neuroimaging techniques offer complementary information and have different methodologic strengths and weaknesses.

Preoperative Functional Mapping for Rolandic Brain Tumor Surgery: Comparison of Navigated Transcranial Magnetic Stimulation to Direct Cortical Stimulation

BACKGROUND:Transcranial magnetic stimulation (TMS) is the only noninvasive method for presurgical stimulation mapping of cortical function. Recent technical advancements have significantly increased the focality and usability of the method. OBJECTIVE:To compare the accuracy of a 3-dimensional magnetic resonance imaging-navigated TMS system (nTMS) with the gold standard of direct cortical stimulation (DCS). METHODS:The primary motor areas of 20 patients with rolandic tumors were mapped preoperatively with nTMS at 110% of the individual resting motor threshold. Intraoperative DCS was available from 17 patients. The stimulus locations eliciting the largest electromyographic response in the target muscles (“hotspots”) were determined for both methods. RESULTS:The nTMS and DCS hotspots were located on the same gyrus in all cases. The mean ± SEM distance between the nTMS and DCS hotspots was 7.83 ± 1.18 mm for the abductor pollicis brevis (APB) muscle (n = 15) and 7.07 ± 0.88 mm for the tibialis anterior muscle (n = 8). When a low number of DCS stimulations was performed, the distance between the nTMS and DCS hotspots increased substantially (r = −0.86 for APB). After the exclusion of the cases with < 15 DCS APB responses, the mean ± SEM distance between the hotspots was only 4.70 ± 1.09 mm for APB (n = 8). CONCLUSION:Peritumoral mapping of the motor cortex by nTMS agreed well with the gold standard of DCS. Thus, nTMS is a reliable tool for preoperative mapping of motor function.

Effects of GABAA and GABAB agonists on interhemispheric inhibition in man

OBJECTIVE Animal studies on neurotransmitter systems that mediate interhemispheric inhibition (IHI) suggest that, (i) callosal transmission is regulated by presynaptic GABA(B) receptors, and (ii) GABA(A)-ergic neurones mediate early IHI, whereas GABA(B)-ergic neurones mediate later IHI. In humans the mechanism is unclear. Interactions between cortical inhibitory circuits suggest a postsynaptic GABA(B)-ergic mechanism. We will here test this hypothesis. METHODS Short-latency IHI (s-IHI) and long-latency IHI (l-IHI) were evaluated using the paired pulse paradigm before and under medication with (i) a GABA(B)-agonist (baclofen) in 17 subjects, and (ii) a GABA(A)-agonist (midazolam) in 10 subjects participating twice. RESULTS Baclofen did not significantly enhance s-IHI. L-IHI between 20 and 50ms was significantly strengthened, and obtained also at ISIs between 100 and 200ms. Midazolam had no effect on s-IHI, whereas l-IHI was attenuated. CONCLUSIONS Our results support the hypothesis, that l-IHI in humans is mediated by postsynaptic GABA(B) receptors. GABA(A)-ergic medication resulted in attenuation of l-IHI. Regarding s-IHI, our results are inconclusive and require further investigation. SIGNIFICANCE This is the first human study evaluating the effect of baclofen on IHI, indicating that l-IHI is mediated by GABA(B)-ergic neurones. Because interhemispheric interaction is now also been used as a therapeutic approach, understanding the underlying neurotransmitter systems will be increasingly relevant.

Long-term reorganization of motor cortex outputs after arm amputation

Objective: To investigate the reorganization of the corticospinal system long after arm amputation at different levels. Methods: Focal transcranial magnetic stimulation (TMS) was performed in 15 patients 21 to 65 years after arm amputation at the level of the forearm, upper arm, or shoulder. Cortically elicited electromyographic responses were investigated in muscles immediately proximal to the stump. TMS was performed on a skull surface grid overlying the motor cortex. The response threshold, number of effective stimulation sites, and the sum of the amplitudes elicited at these sites were evaluated for slightly contracted muscles. Results: Seven of eight patients with forearm amputation had larger stimulation effects in the biceps supplied by the motor cortex contralateral to amputation, as indicated by variable patterns of lowered response thresholds, increased response amplitudes, or increased numbers of effective stimulation sites. In seven patients with a more proximal amputation, the motor responses were investigated in the deltoid and trapezoid muscle. In only two of them, the motor cortex contralateral to amputation showed an increased excitability. Three patients presented with a higher excitability of the motor cortex contralateral to the intact arm and two with a balanced type of excitability. Conclusion: Reorganization of the motor system can be present more than 20 years after amputation. Furthermore, differential patterns of reorganized corticospinal output were found for different stump muscles, which might be due to varying amounts of ipsilateral corticospinal projections.

Transcranial direct current stimulation affects visual perception measured by threshold perimetry.

In this study, we aimed to characterize the effect of anodal and cathodal direct current stimulation (tDCS) on contrast sensitivity inside the central 10 degrees of the visual field in healthy subjects. Distinct eccentricities were investigated separately, since at the cortical level, more central regions of the visual field are represented closer to the occipital pole, i.e. closer to the polarizing electrodes, than are the more peripheral regions. Using a double-blind and sham-controlled within-subject design, we measured the effect of stimulation and potential learning effect separately across testing days. Anodal stimulation of the visual cortex compared to sham stimulation yielded a significant increase in contrast sensitivity within 8° of the visual field. A significant increase in contrast sensitivity between the conditions “pre” and “post” anodal stimulation was only obtained for the central positions at eccentricities smaller than 2°. Cathodal stimulation of the visual cortex did not affect contrast sensitivity at either eccentricity. Perceptual learning across testing days was only observed for threshold perimetry before stimulation. Measuring contrast sensitivity changes after tDCS with a standard clinical tool such as threshold perimetry may provide an interesting perspective in assessing therapeutic effects of tDCS in ophthalmological or neurological defects (e.g. with foveal sparing vs. foveal splitting).

An initial transient-state and reliable measures of corticospinal excitability in TMS studies

OBJECTIVE The objective of this study was to determine if an initial transient state influences the acquisition of reliable estimates of corticospinal excitability in transcranial magnetic stimulation (TMS) studies. Whereas muscle evoked potential (MEP) amplitudes are an important index of cortical excitability, these are severely limited by sweep-to-sweep variability. Interesting in this context is the experimental observation that the first MEP amplitudes might be much larger than subsequent responses [Brasil-Neto JP, Cohen LG, Hallet M. Central fatigue as revealed by postexercise decrement of motor evoked potentials. Muscle Nerve 1994;17:713-9]. This led to the hypothesis that an initial transient-state of increased excitability affects MEP amplitude derived estimates of corticospinal excitability. METHODS To address this issue we acquired repeated measures of single pulse MEP amplitudes over the primary motor cortex with and without navigated brain stimulation (NBS) and with various TMS-coils. Importantly, NBS allows for the sweep-to-sweep differentiation of physical and physiological variability. RESULTS We found a significant decline in estimates of corticospinal excitability and a transition from log-Normal to Normal distributed state, after which reliable measures (British Standards Institute) could be acquired. CONCLUSIONS We argue that an initial transient state of physiological origin influences measures of corticospinal excitability. SIGNIFICANCE This has important implications for investigations of cortical excitability. For example, it could reduce variability over studies and within small group comparisons.

Modulation of motor cortex excitability by pallidal stimulation in patients with severe dystonia

Objective: To study the influence of continuous high-frequency electrical stimulation with electrodes implanted in the globus pallidus internus (GPi) on motor cortex excitability in nine patients with dystonia. Methods: Short-term effects related to switching off and on the deep brain stimulator were investigated >3 months after electrode implantation. Activation of motor cortical excitatory and inhibitory neurons was examined with transcranial magnetic stimulation (TMS) by analysis of electromyographic activity in the hand muscles. Parameters of corticospinally mediated excitatory motor responses included latency, threshold, and response sizes with increasing stimulus intensities (stimulus–response curves). Other measures of motor cortex excitability comprised the duration of the contralateral silent period and intracortical inhibition and facilitation in a paired-pulse paradigm. Results: Switching off GPi stimulation led to a decrease of motor cortex excitability, as reflected by an increase in motor thresholds (GPi stimulation on 37.5 ± 6.1%, mean ± SD; GPi stimulation off for 15 to 120 minutes, 40.5 ± 6.7% of maximum stimulator output), and reduced the size of contralateral responses in the stimulus–response curves established for relaxed muscles. The changes were reversible within minutes after switching on GPi stimulation. They were associated with mild changes of dystonia. By contrast, measures of intracortical inhibition were not altered by switching off GPi stimulation. Spinal excitability did not change as assessed by H-reflex. Conclusion: GPi stimulation influences motor cortex excitability by a rapid modulation of thalamocortical outputs.

Spatial memory deficits in patients with lesions affecting the medial temporal neocortex.

Lesion studies in monkeys suggest that neocortical subregions of the medial temporal lobe (MTL) carry memory functions independent of the hippocampal formation. The present study investigates possible differential contributions of MTL subregions to spatial memory in humans. Eye movements toward remembered spatial cues (memory‐guided saccades) with unpredictably varied memorization delays of up to 30 seconds were recorded in patients with postsurgical lesions of the right MTL, either restricted to the hippocampal formation (n = 3) or including the adjacent neocortex (n = 5) and in 10 controls. Although saccadic targeting errors of patients with selective hippocampal lesions did not differ from controls, saccadic targeting errors of patients with additional neocortical involvement showed a significant and contralaterally pronounced increase at memorization delays above 20 seconds. We conclude that the human medial temporal neocortex carries spatial memory functions independent of the hippocampal formation and distinct from spatial short‐term memory. Ann Neurol 1999;45:312–319