Felix Blankenburg

Correlates of alpha rhythm in functional magnetic resonance imaging and near infrared spectroscopy

We used simultaneous electroencephalogram-functional magnetic resonance imaging (EEG-fMRI) and EEG-near infrared spectroscopy (NIRS) to investigate whether changes of the posterior EEG alpha rhythm are correlated with changes in local cerebral blood oxygenation. Cross-correlation analysis of slowly fluctuating, spontaneous rhythms in the EEG and the fMRI signal revealed an inverse relationship between alpha activity and the fMRI-blood oxygen level dependent signal in the occipital cortex. The NIRS-EEG measurements demonstrated a positive cross-correlation in occipital cortex between alpha activity and concentration changes of deoxygenated hemoglobin, which peaked at a relative shift of about 8 s. Our data suggest that alpha activity in the occipital cortex is associated with metabolic deactivation. Mapping of spontaneously synchronizing distributed neuronal networks is thus shown to be feasible.

Concurrent TMS-fMRI and Psychophysics Reveal Frontal Influences on Human Retinotopic Visual Cortex

BACKGROUND Regions in human frontal cortex may have modulatory top-down influences on retinotopic visual cortex, but to date neuroimaging methods have only been able to provide indirect evidence for such functional interactions between remote but interconnected brain regions. Here we combined transcranial magnetic stimulation (TMS) with concurrent functional magnetic resonance imaging (fMRI), plus psychophysics, to show that stimulation of the right human frontal eye-field (FEF) produced a characteristic topographic pattern of activity changes in retinotopic visual areas V1-V4, with functional consequences for visual perception. RESULTS FEF TMS led to activity increases for retinotopic representations of the peripheral visual field, but to activity decreases for the central field, in areas V1-V4. These frontal influences on visual cortex occurred in a top-down manner, independently of visual input. TMS of a control site (vertex) did not elicit such visual modulations, and saccades, blinks, or pupil dilation could not account for our results. Finally, the effects of FEF TMS on activity in retinotopic visual cortex led to a behavioral prediction that we confirmed psychophysically by showing that TMS of the frontal site (again compared with vertex) enhanced perceived contrast for peripheral relative to central visual stimuli. CONCLUSIONS Our results provide causal evidence that circuits originating in the human FEF can modulate activity in retinotopic visual cortex, in a manner that differentiates the central and peripheral visual field, with functional consequences for perception. More generally, our study illustrates how the new approach of concurrent TMS-fMRI can now reveal causal interactions between remote but interconnected areas of the human brain.

Mapping causal interregional influences with concurrent TMS-fMRI

Transcranial magnetic stimulation (TMS) produces a direct causal effect on brain activity that can now be studied by new approaches that simultaneously combine TMS with neuroimaging methods, such as functional magnetic resonance imaging (fMRI). In this review we highlight recent concurrent TMS–fMRI studies that illustrate how this novel combined technique may provide unique insights into causal interactions among brain regions in humans. We show how fMRI can detect the spatial topography of local and remote TMS effects and how these may vary with psychological factors such as task-state. Concurrent TMS–fMRI may furthermore reveal how the brain adapts to so-called virtual lesions induced by TMS, and the distributed activity changes that may underlie the behavioural consequences often observed during cortical stimulation with TMS. We argue that combining TMS with neuroimaging techniques allows a further step in understanding the physiological underpinnings of TMS, as well as the neural correlated of TMS-evoked consequences on perception and behaviour. This can provide powerful new insights about causal interactions among brain regions in both health and disease that may ultimately lead to developing more efficient protocols for basic research and therapeutic TMS applications.

The Role of Contralesional Dorsal Premotor Cortex after Stroke as Studied with Concurrent TMS-fMRI

Contralesional dorsal premotor cortex (cPMd) may support residual motor function following stroke. We performed two complementary experiments to explore how cPMd might perform this role in a group of chronic human stroke patients. First, we used paired-coil transcranial magnetic stimulation (TMS) to establish the physiological influence of cPMd on ipsilesional primary motor cortex (iM1) at rest. We found that this influence became less inhibitory/more facilitatory in patients with greater clinical impairment. Second, we applied TMS over cPMd during functional magnetic resonance imaging (fMRI) in these patients to examine the causal influence of cPMd TMS on the whole network of surviving cortical motor areas in either hemisphere and whether these influences changed during affected hand movement. We confirmed that hand grip-related activation in cPMd was greater in more impaired patients. Furthermore, the peak ipsilesional sensorimotor cortex activity shifted posteriorly in more impaired patients. Critical new findings were that concurrent TMS-fMRI results correlated with the level of both clinical impairment and neurophysiological impairment (i.e., less inhibitory/more facilitatory cPMd-iM1 measure at rest as assessed with paired-coil TMS). Specifically, greater clinical and neurophysiological impairment was associated with a stronger facilitatory influence of cPMd TMS on blood oxygenation level-dependent signal in posterior parts of ipsilesional sensorimotor cortex during hand grip, corresponding to the posteriorly shifted sensorimotor activity seen in more impaired patients. cPMd TMS was not found to influence activity in other brain regions in either hemisphere. This state-dependent influence on ipsilesional sensorimotor regions may provide a mechanism by which cPMd supports recovered function after stroke.

Hemispheric differences in frontal and parietal influences on human occipital cortex: Direct confirmation with concurrent tms-fmri

We used concurrent TMS–fMRI to test directly for hemispheric differences in causal influences of the right or left fronto-parietal cortex on activity (BOLD signal) in the human occipital cortex. Clinical data and some behavioral TMS studies have been taken to suggest right-hemisphere specialization for top–down modulation of vision in humans, based on deficits such as spatial neglect or extinction in lesioned patients, or findings that TMS to right (vs. left) fronto-parietal structures can elicit stronger effects on visual performance. But prior to the recent advent of concurrent TMS and neuroimaging, it was not possible to directly examine the causal impact of one (stimulated) brain region upon others in humans. Here we stimulated the frontal or intraparietal cortex in the left or right hemisphere with TMS, inside an MR scanner, while measuring with fMRI any resulting BOLD signal changes in visual areas V1–V4 and V5/MT+. For both frontal and parietal stimulation, we found clear differences between effects of right- versus left-hemisphere TMS on activity in the visual cortex, with all differences significant in direct statistical comparisons. Frontal TMS over either hemisphere elicited similar BOLD decreases for central visual field representations in V1–V4, but only right frontal TMS led to BOLD increases for peripheral field representations in these regions. Hemispheric differences for effects of parietal TMS were even more marked: Right parietal TMS led to strong BOLD changes in V1–V4 and V5/MT+, but left parietal TMS did not. These data directly confirm that the human frontal and parietal cortex show right-hemisphere specialization for causal influences on the visual cortex.

Concurrent brain-stimulation and neuroimaging for studies of cognition

Neuroimaging can address activity across the entire brain in relation to cognition, but is typically correlative rather than causal. Brain stimulation can target a local brain area causally, but without revealing the entire network affected. Combining brain stimulation with concurrent neuroimaging allows a new causal approach to how interplay between extended networks of brain regions can support cognition. Brain stimulation does not affect only the targeted local region but also activity in remote interconnected regions. These remote effects depend on cognitive factors (e.g. task-condition), revealing dynamic changes in interplay between brain areas. We illustrate this with examples from top-down modulation of visual cortex, response-competition, inter-hemispheric rivalry and motor tasks; but the new approach should be applicable to many domains of cognition.

The cutaneous rabbit illusion affects human primary sensory cortex somatotopically.

We used functional magnetic resonance imaging (fMRI) to study neural correlates of a robust somatosensory illusion that can dissociate tactile perception from physical stimulation. Repeated rapid stimulation at the wrist, then near the elbow, can create the illusion of touches at intervening locations along the arm, as if a rabbit hopped along it. We examined brain activity in humans using fMRI, with improved spatial resolution, during this version of the classic cutaneous rabbit illusion. As compared with control stimulation at the same skin sites (but in a different order that did not induce the illusion), illusory sequences activated contralateral primary somatosensory cortex, at a somatotopic location corresponding to the filled-in illusory perception on the forearm. Moreover, the amplitude of this somatosensory activation was comparable to that for veridical stimulation including the intervening position on the arm. The illusion additionally activated areas of premotor and prefrontal cortex. These results provide direct evidence that illusory somatosensory percepts can affect primary somatosensory cortex in a manner that corresponds somatotopically to the illusory percept.

Causal Role of Dorsolateral Prefrontal Cortex in Human Perceptual Decision Making

The way that we interpret and interact with the world entails making decisions on the basis of available sensory evidence. Recent primate neurophysiology [1-6], human neuroimaging [7-13], and modeling experiments [14-19] have demonstrated that perceptual decisions are based on an integrative process in which sensory evidence accumulates over time until an internal decision bound is reached. Here we used repetitive transcranial magnetic stimulation (rTMS) to provide causal support for the role of the dorsolateral prefrontal cortex (DLPFC) in this integrative process. Specifically, we used a speeded perceptual categorization task designed to induce a time-dependent accumulation of sensory evidence through rapidly updating dynamic stimuli and found that disruption of the left DLPFC with low-frequency rTMS reduced accuracy and increased response times relative to a sham condition. Importantly, using the drift-diffusion model, we show that these behavioral effects correspond to a decrease in drift rate, a parameter describing the rate and thereby the efficiency of the sensory evidence integration in the decision process. These results provide causal evidence linking the DLPFC to the mechanism of evidence accumulation during perceptual decision making.

Influence of uncertainty and surprise on human corticospinal excitability during preparation for action.

Summary Actions are guided by prior sensory information [1–10], which is inherently uncertain. However, how the motor system is sculpted by trial-by-trial content of current sensory information remains largely unexplored. Previous work suggests that conditional probabilities, learned under a particular context, can be used preemptively to influence the output of the motor system [11–14]. To test this we used transcranial magnetic stimulation (TMS) to read out corticospinal excitability (CSE) during preparation for action in an instructed delay task [15, 16]. We systematically varied the uncertainty about an impending action by changing the validity of the instructive visual cue. We used two information-theoretic quantities to predict changes in CSE, prior to action, on a trial-by-trial basis: entropy (average uncertainty) and surprise (the stimulus-bound information conveyed by a visual cue) [17–19]. Our data show that during preparation for action, human CSE varies according to the entropy and surprise conveyed by visual events guiding action. CSE increases on trials with low entropy about the impending action and low surprise conveyed by an event. Commensurate effects were observed in reaction times. We suggest that motor output is biased according to contextual probabilities that are represented dynamically in the brain.

Studying the Role of Human Parietal Cortex in Visuospatial Attention with Concurrent TMS–fMRI

Combining transcranial magnetic stimulation (TMS) with concurrent functional magnetic resonance imaging (fMRI) allows study of how local brain stimulation may causally affect activity in remote brain regions. Here, we applied bursts of high- or low-intensity TMS over right posterior parietal cortex, during a task requiring sustained covert visuospatial attention to either the left or right hemifield, or in a neutral control condition, while recording blood oxygenation-level–dependent signal with a posterior MR surface coil. As expected, the active attention conditions activated components of the well-described “attention network,” as compared with the neutral baseline. Also as expected, when comparing left minus right attention, or vice versa, contralateral occipital visual cortex was activated. The critical new finding was that the impact of high- minus low-intensity parietal TMS upon these visual regions depended on the currently attended side. High- minus low-intensity parietal TMS increased the difference between contralateral versus ipsilateral attention in right extrastriate visual cortex. A related albeit less pronounced pattern was found for left extrastriate visual cortex. Our results confirm that right human parietal cortex can exert attention-dependent influences on occipital visual cortex and provide a proof of concept for the use of concurrent TMS–fMRI in studying how remote influences can vary in a purely top–down manner with attentional demands.