Asymmetry of parietal interhemispheric connections in humans

Visuospatial abilities are preferentially mediated by the right hemisphere. Although this asymmetry of function is thought to be due to an unbalanced interaction between cerebral hemispheres, the underlying neurophysiological substrate is still largely unknown. Here, using a method of trifocal transcranial magnetic stimulation, we show that the right, but not left, human posterior parietal cortex exerts a strong inhibitory activity over the contralateral homologous area by a short-latency connection. We also clarify, using diffusion-tensor magnetic resonance imaging, that such an interaction is mediated by direct transcallosal projections located in the posterior corpus callosum. We argue that this anatomo-functional network may represent a possible neurophysiological basis for the ongoing functional asymmetry between parietal cortices, and that its damage could contribute to the clinical manifestations of neglect

Excitatory postsynaptic potentials in rat neocortical neurons in vitro. III. Effects of a quinoxalinedione non-NMDA receptor antagonist

1. Intracellular microelectrodes were used to obtain recordings from neurons in layer II/III of rat frontal cortex. A bipolar electrode positioned in layer IV of the neocortex was used to evoke postsynaptic potentials. Graded series of stimulation were employed to selectively activate different classes of postsynaptic responses. The sensitivity of postsynaptic potentials and iontophoretically applied neurotransmitters to the non-N-methyl-D-asparate (NMDA) antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) was examined. 2. As reported previously, low-intensity electrical stimulation of cortical layer IV evoked short-latency early excitatory postsynaptic potentials (eEPSPs) in layer II/III neurons. CNQX reversibly antagonized eEPSPs in a dose-dependent manner. Stimulation at intensities just subthreshold for activation of inhibitory postsynaptic potentials (IPSPs) produced long-latency (10 to 40-ms) EPSPs (late EPSPs or 1EPSPs). CNQX was effective in blocking 1EPSPs. 3. With the use of stimulus intensities at or just below threshold for evoking an action potential, complex synaptic potentials consisting of EPSP-IPSP sequences were observed. Both early, Cl(-)-dependent and late, K(+)-dependent IPSPs were reduced by CNQX. This effect was reversible on washing. This disinhibition could lead to enhanced excitability in the presence of CNQX. 4. Iontophoretic application of quisqualate produced a membrane depolarization with superimposed action potentials, whereas NMDA depolarized the membrane potential and evoked bursts of action potentials. At concentrations up to 5 microM, CNQX selectively antagonized quisqualate responses. NMDA responses were reduced by 10 microM CNQX. D-Serine (0.5-2 mM), an agonist at the glycine regulatory site on the NMDA receptor, reversed the CNQX depression of NMDA responses

Investigation of the neural control of cough and cough suppression in humans using functional brain imaging

Excessive coughing is one of the mostcommonreasons for seeking medical advice, yet the available therapies for treating cough disorders are inadequate. Humans can voluntarily cough, choose to suppress their cough, and are acutely aware of an irritation that is present in their airways. This indicates a significant level of behavioral and conscious control over the basic cough reflex pathway. However, very little is known about the neural basis for higher brain regulation of coughing. The aim of the present study was to use functional brain imaging in healthy humans to describe the supramedullary control of cough and cough suppression. Our data show that the brain circuitry activated during coughing in response to capsaicin-evoked airways irritation is not simply a function of voluntarily initiated coughing and the perception of airways irritation. Rather, activations in several brain regions, including the posterior insula and posterior cingulate cortex, define the unique attributes of an evoked cough. Furthermore, the active suppression of irritant-evoked coughing is also associated with a unique pattern of brain activity, including an involvement of the anterior insula, anterior mid-cingulate cortex, and inferior frontal gyrus. These data demonstrate for the first time that evoked cough is not solely a brainstem-mediated reflex response to irritation of the airways, but rather requires active facilitation by cortical regions, and is further regulated by distinct higher order inhibitory processes. Copyright © 2011 the authors

Transcranial magnetic stimulation and EEG in studies of brain function

Transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) is a multimodal technique, with a temporal resolution of submilliseconds, for studying cortical excitability and connectivity. When TMS is combined with neuronavigation, resulting in so-called navigated TMS (nTMS), the technique becomes very powerful. However, despite the potential of TMS–EEG, its use for studying lateral areas has been restricted because the TMS pulse induces strong muscle artifacts, making the EEG data useless for further analyses. In this Thesis, methods for analyzing TMS-evoked EEG data from lateral areas are introduced. First, TMS–EEG is used to study Broca's area and dorsal premotor cortex. Due to the fact that those areas are close to cranial muscles, their stimulation evokes large muscle artifacts in EEG recordings. The behavior of the artifacts is described in detail. Two approaches to deal with large artifacts are presented. In the first approach, independent component analysis (ICA) is used. Here, FastICA algorithm is modified to make the search of the components more robust and easier, allowing one to get more stable results. The second approach presents methods for suppressing the artifacts rather than removing them. These methods were combined with source localization showing that the artifact suppression is efficient. The methods were tested with both real and simulated data, suggesting they are useful for artifact correction. For a better understanding of the effects of repetitive nTMS during naming tasks and the cortical organization of speech in general, here another study is introduced to understand the sensitivity of object and action naming tasks to repetitive nTMS. The distributions of cortical sites, where repetitive nTMS produced naming errors during both tasks, are compared. Thus, it is shown how this study can impact on both cognitive neuroscience and clinical practice. In the last part, the beamformer method is improved to study source localization, which makes it a robust method to study time-correlated sources. In this Thesis, I discuss how all these methods together can contribute to study brain connectivity of language and lateral areas with TMS–EEG, opening new possibilities for basic research and clinical applications

Resolving the brainstem contributions to attentional analgesia

Previous human imaging studies manipulating attention or expectancy have identified the periaqueductal gray (PAG) as a key brainstem structure implicated in endogenous analgesia. However, animal studies indicate that PAG analgesia is mediated largely via caudal brainstem structures, such as the rostral ventromedial medulla (RVM) and locus coeruleus (LC). To identify their involvement in endogenous analgesia, we used brainstem optimized, whole-brain imaging to record responses to concurrent thermal stimulation (left forearm) and visual attention tasks of titrated difficulty in 20 healthy subjects. The PAG, LC, and RVM were anatomically discriminated using a probabilistic atlas. Pain ratings disclosed the anticipated analgesic interaction between task difficulty and pain intensity (p < 0.001). Main effects of noxious thermal stimulation were observed across several brain regions, including operculoinsular, primary somatosensory, and cingulate cortices, whereas hard task difficulty was represented in anterior insular, parietal, and prefrontal cortices. Permutation testing within the brainstem nuclei revealed the following: main effects of task in dorsal PAG and right LC; and main effect of temperature in RVM and a task × temperature interaction in right LC. Intrasubject regression revealed a distributed network of supratentorial brain regions and the RVM whose activity was linearly related to pain intensity. Intersubject analgesia scores correlated to activity within a distinct region of the RVM alone. These results identify distinct roles for a brainstem triumvirate in attentional analgesia: with the PAG activated by attentional load; specific RVM regions showing pronociceptive and antinociceptive processes (in line with previous animal studies); and the LC showing lateralized activity during conflicting attentional demands. SIGNIFICANCE STATEMENT Attention modulates pain intensity, and human studies have identified roles for a network of forebrain structures plus the periaqueductal gray (PAG). Animal data indicate that the PAG acts via caudal brainstem structures to control nociception. We investigated this issue within an attentional analgesia paradigm with brainstem-optimized fMRI and analysis using a probabilistic brainstem atlas. We find pain intensity encoding in several forebrain structures, including the insula and attentional activation of the PAG. Discrete regions of the rostral ventromedial medulla bidirectionally influence pain perception, and locus coeruleus activity mirrors the interaction between attention and nociception. This approach has enabled the resolution of contributions from a hub of key brainstem structures to endogenous analgesia

Visual recognition memory: a view from V1

Although work in primates on higher-order visual areas has revealed how the individual and concerted activity of neurons correlates with behavioral reports of object recognition, very little is known about the underlying mechanisms for visual recognition memory. Low-level vision, even as early as primary visual cortex (V1) and even in subjects as unsophisticated as rodents, promises to fill this void. Although this latter approach sacrifices interrogation of many of the most astounding features of visual recognition, it does provide experimental constraint, proximity to sensory input, and a wide range of interventional approaches. The tractability of rodent visual cortex promises to reveal the molecular mechanisms and circuits that are essential for a fundamental form of memory.National Eye Institute (Grant RO1EY023037

Studying the cortical state with transcranial magnetic stimulation

Cortical excitability and connectivity describe the state of the cerebral cortex. They reflect the ability of neurons to respond to input and the way information flows in the neuronal networks. These properties can be assessed with transcranial magnetic stimulation (TMS), which enables direct and noninvasive modulation of cortical activity. Electrophysiological or hemodynamic recordings of TMS-evoked activity or behavioral measures of the stimulation effect characterize the state of the cortex during and as a result of the stimulation. In the research reported in this Thesis, the ability of TMS to inform us about the cortical state is studied from different points of view. First, we examine the relationships between different measures of cortical excitability to better understand the physiology behind them; we show how cortical background activity is related to motor cortical excitability and how the evoked responses reflect the excitability. Second, this study addresses the questions whether the TMS-evoked responses include stimulation-related artifacts, how these artifacts are generated, and how they can be avoided or removed. Specifically, we present a method to remove the artifacts from TMS-evoked electroencephalographic (EEG) signals arising as a result of cranial muscle stimulation. The use of TMS-EEG has been limited to relatively medial sites because of these artifacts, but the new method enables studying the cortical state even when stimulating areas near the cranial muscles, especially lateral sites. Finally, this work provides new information about brain function. The mechanisms how the brain processes visually guided timed motor actions are elucidated. Moreover, we show that cortical excitability as measured with TMS-evoked EEG increases during the course of wakefulness and decreases during sleep, which contributes to our understanding of what happens in the brain during wakefulness that makes us feel tired and why the brain needs sleep. The study also shows the sensitivity of the TMS-EEG measurement to changes in the state of the cortex. Accordingly, we demonstrate the power of TMS in studying the cortical state

Frontal eye field, where art thou? Anatomy, function, and non-invasive manipulation of frontal regions involved in eye movements and associated cognitive operations

The planning, control and execution of eye movements in 3D space relies on a distributed system of cortical and subcortical brain regions. Within this network, the Eye Fields have been described in animals as cortical regions in which electrical stimulation is able to trigger eye movements and influence their latency or accuracy. This review focuses on the Frontal Eye Field (FEF) a “hub” region located in Humans in the vicinity of the pre-central sulcus and the dorsal-most portion of the superior frontal sulcus. The straightforward localization of the FEF through electrical stimulation in animals is difficult to translate to the healthy human brain, particularly with non-invasive neuroimaging techniques. Hence, in the first part of this review, we describe attempts made to characterize the anatomical localization of this area in the human brain. The outcome of functional Magnetic Resonance Imaging (fMRI), Magneto-encephalography (MEG) and particularly, non-invasive mapping methods such a Transcranial Magnetic Stimulation (TMS) are described and the variability of FEF localization across individuals and mapping techniques are discussed. In the second part of this review, we will address the role of the FEF. We explore its involvement both in the physiology of fixation, saccade, pursuit, and vergence movements and in associated cognitive processes such as attentional orienting, visual awareness and perceptual modulation. Finally in the third part, we review recent evidence suggesting the high level of malleability and plasticity of these regions and associated networks to non-invasive stimulation. The exploratory, diagnostic, and therapeutic interest of such interventions for the modulation and improvement of perception in 3D space are discussed