Drawing cartoon faces - a functional imaging study of the cognitive neuroscience of drawing

We report a functional imaging study of drawing cartoon faces. Normal, untrained participants were scanned while viewing simple black and white cartoon line-drawings of human faces, retaining them for a short memory interval, and then drawing them without vision of their hand or the paper. Specific encoding and retention of information about the faces was tested for by contrasting these two stages (with display of cartoon faces) against the exploration and retention of random dot stimuli. Drawing was contrasted between conditions in which only memory of a previously viewed face was available versus a condition in which both memory and simultaneous viewing of the cartoon was possible, and versus drawing of a new, previously unseen, face. We show that the encoding of cartoon faces powerfully activates the face sensitive areas of the lateral occipital cortex and the fusiform gyrus, but there is no significant activation in these areas during the retention interval. Activity in both areas was also high when drawing the displayed cartoons. Drawing from memory activates areas in posterior parietal cortex and frontal areas. This activity is consistent with the encoding and retention of the spatial information about the face to be drawn as a visuo-motor action plan, either representing a series of targets for ocular fixation or as spatial targets for the drawing actio

Methodological Problems in fMRI Studies on Acupuncture: A Critical Review with Special Emphasis on Visual and Auditory Cortex Activations

Functional magnetic resonance imaging (fMRI) has been used for more than a decade to investigate possible supraspinal mechanisms of acupuncture stimulation. More than 60 studies and several review articles have been published on the topic. However, till now some acupuncture-fMRI studies have not adopted all methodological standards applied to most other fMRI studies. In this critical review, we comment on some of the problems including the choice of baseline, interpretation of deactivations, attention control and implications of different group statistics. We illustrate the possible impact of these problems by focussing on some early findings, namely activations of visual and auditory cortical areas, when acupoints were stimulated that are believed to have a therapeutic effect on vision or hearing in traditional Chinese medicine. While we are far from questioning the validity of using fMRI for the study of acupuncture effects, we think that activations reported by some of these studies were probably not a direct result of acupuncture stimulation but rather attributable to one or more of the methodological problems covered here. Finally, we try to offer solutions for these problems where possible

Glutamatergic and Resting-State Functional Connectivity Correlates of Severity in Major Depression – The Role of Pregenual Anterior Cingulate Cortex and Anterior Insula

Glutamatergic mechanisms and resting-state functional connectivity alterations have been recently described as factors contributing to major depressive disorder (MDD). Furthermore, the pregenual anterior cingulate cortex (pgACC) seems to play an important role for major depressive symptoms such as anhedonia and impaired emotion processing. We investigated 22 MDD patients and 22 healthy subjects using a combined magnetic resonance spectroscopy (MRS) and resting-state functional magnetic resonance imaging (fMRI) approach. Severity of depression was rated using the 21-item Hamilton depression scale (HAMD) and patients were divided into severely and mildly depressed subgroups according to HAMD scores. Because of their hypothesized role in depression we investigated the functional connectivity between pgACC and left anterior insular cortex (AI). The sum of Glutamate and Glutamine (Glx) in the pgACC, but not in left AI, predicted the resting-state functional connectivity between the two regions exclusively in depressed patients. Furthermore, functional connectivity between these regions was significantly altered in the subgroup of severely depressed patients (HAMD > 15) compared to healthy subjects and mildly depressed patients. Similarly the Glx ratios, relative to Creatine, in the pgACC were lowest in severely depressed patients. These findings support the involvement of glutamatergic mechanisms in severe MDD which are related to the functional connectivity between pgACC and AI and depression severity

Drawing cartoon faces - a functional imaging study of the cognitive neuroscience of drawing.

We report a functional imaging study of drawing cartoon faces. Normal, untrained participants were scanned while viewing simple black and white cartoon line-drawings of human faces, retaining them for a short memory interval, and then drawing them without vision of their hand or the paper. Specific encoding and retention of information about the faces was tested for by contrasting these two stages (with display of cartoon faces) against the exploration and retention of random dot stimuli. Drawing was contrasted between conditions in which only memory of a previously viewed face was available versus a condition in which both memory and simultaneous viewing of the cartoon was possible, and versus drawing of a new, previously unseen, face. We show that the encoding of cartoon faces powerfully activates the face sensitive areas of the lateral occipital cortex and the fusiform gyrus, but there is no significant activation in these areas during the retention interval. Activity in both areas was also high when drawing the displayed cartoons. Drawing from memory activates areas in posterior parietal cortex and frontal areas. This activity is consistent with the encoding and retention of the spatial information about the face to be drawn as a visuo-motor action plan, either representing a series of targets for ocular fixation or as spatial targets for the drawing action

Characterizing Resting Cerebral Blood Flow in Obsessive-Compulsive Disorder with Arterial Spin Labeling

Obsessive-compulsive disorder (OCD) is a condition characterized by intrusive thoughts (obsessions) and ritualistic behaviors (compulsions) profoundly impacting daily functioning and quality of life. Neuroimaging studies using various techniques have revealed inconsistent resting cerebral blood flow (rCBF) patterns in OCD patients, particularly within the cortico-striatal-thalamo-cortical (CSTC) circuit and sensorimotor network. Arterial Spin Labeling (ASL) MRI offers a promising, noninvasive method for directly measuring rCBF. This study, using data from the Yale HCP Trio study, analyzed unmedicated OCD patients and healthy controls, who underwent two consecutive resting pulsed-ASL scans. OCD patients with lower obsessional severity exhibited higher perfusion in the pre- and postcentral gyri, indicating potential sensorimotor circuit dysregulation. However, no other results survived FDR correction. Interestingly, highly obsessional OCD patients did not show increased sensorimotor perfusion, relative to HCs, suggesting potential differences in cognitive processes during rest (e.g., obsessing, rather than mind-wandering). Future investigations should explore perfusion differences across OCD severity levels, considering individual differences in obsession type and cognitive processes at rest to better characterize group differences in rCBF

Brain Energy

Abstract Following the pragmatic practices of anesthesiologists, a person is defined to be in the state of consciousness by the ability to respond to stimuli. C Magnetic Resonance Spectroscopy (MRS), Positron Emission Tomography (PET), and electrophysiology experiments have been directed towards these goals. These studies have measured brain energy production in the form of glucose oxidation in the resting baseline and anesthetized states and have followed regional changes during stimulation from these states. PET and MRS methods have measured the total or baseline energies while neuroimaging studies, by fMRI and PET, have determined the incremental energies during cognitive or sensory stimulations. The most striking result is that the energy consumption supporting neuronal firing in the conscious-awake, baseline state is one to two orders of magnitude larger than the energy changes during stimulation Early functional imaging studies by It soon became clear, however, that the brain did not follow the simple assumptions of "pure insertion" which expects the incremental brain neuronal response to a mental process to be independent of its context. The dependence of brain responses upon their context created problems for cognitive psychology, which had assumed, for example, that all acts of remembering would require brain to use a similar module of "memory". Jerry Fodor, a founder of the field, concluded in 2000 that this original formulation was not supported experimentally and in his book with that title recognized that "the mind does not work that way" In the face of these results, prominent neuroimagers tried to retain the potential value of cognitive concepts by considering that the dependence upon context arose from the non-linear nature of brain responses In this report we examine what neuroimaging can tell us about a human in the state of consciousness by using an alternate approach which does not assume that consciousness is supported by hypothesized mental processes. In our study, brain experiments are used to determine neuronal and energetic properties of a behavioral state, as distinguished from the claims that imaging results localize theorized mental processes in the brain. Furthermore, we include a central role for the high baseline level of neuronal activity that is removed by differencing in the large majority of functional imaging studies. In both these respects they offer a previously untried methodology for relating brain activities to observable behavior. We believe that baseline brain activities provide necessary support for behavioral processes that are characteristic of the human or rodent in the state of consciousness. In our view, memory, intent, etcetera are contingent assumptions of mental processes presumed to underlie actions performed by the person. Rather than hypothesizing and then localizing psychological assumptions about the contents of consciousness, in our studies the subjects, rat or human, are defined as being in a conscious state by observations of reproducible behavior. In our definition, the state of consciousness enables a person to perform the many actions that Zeman ( 2002) called the Psyche, Vol 15, No 2 (2009) Brain Energy 62 contents of consciousness. These are the actions, feelings, thoughts, sensory interconnections, etcetera, which are described in common parlance as being caused by mental processes. These observables are postulated in neuroimaging studies to be identified with concepts, for example, memory, attention or recognition, and are then sought in localized brain activities. Uncertainties in this methodology have been revealed by the widely recognized dependence of these concepts upon the context in which they are embedded. To avoid these complexities we are correlating brain activities not with such specific assumptions about the contents of consciousness, but rather with the state of consciousness of a human or of the rat. We describe the state of consciousness simply by the subject's ability to respond to stimuli using the criteria established in anesthesia We propose that high cerebral energy (and by inference its coupled neuronal activity) in the awake state defines a necessary property of the consciousness state; when the energy is reduced sufficiently, there is loss of consciousness. Two additional brain properties that we have measured are the fMRI activation patterns and neuronal population activity with change with baseline state. In this paper, we first review the methods developed (primarily in our laboratory) to measure brain energy consumption and their use in studies of the coupled neuronal signaling, which is the work of the brain (Section I). These studies have shown that, above a relatively small level of non-functional energy, brain energy consumption is coupled to the firing of glutamatergic neurons in the cerebral cortex and the coupled ATP consumption during neuronal signaling (e.g., action and field potentials, neurotransmitter release, and recycling, etc). Then we describe experimental measurements of brain properties of the state of consciousness (Section II). The brain energy distribution and the range of energy consumption in the fully awake state measured by PET and fMRI studies are reviewed. Overall, it is shown that in the state of consciousness, the brain energy, and by inference the neuronal signaling, is evenly distributed throughout the cortex. Fluctuations in energy are small compared to the resting brain energy in the fully awake state. PET reports of subjects undergoing graded anesthesia are then reviewed to show the reduced energy levels (and its regional distribution) at which subjects lose consciousness, as defined by the loss of response to stimuli. Next we discuss two additional brain properties, fMRI activation patterns and the firing rates of neuronal populations that change significantly with baseline energy. Finally, we discuss implications of our proposal that measurable brain properties provide insight to the state of consciousness (Section III). Current definitions, philosophies, and theories for the state of consciousness are discussed to demonstrate how measurable brain properties are beginning to sketch a physical understanding of the interconnected behavior representing that state, without a priori assumptions about underlying mental processes

Applicability of Quantitative Functional MRI Techniques for Studies of Brain Function at Ultra-High Magnetic Field

This thesis describes the development, implementation and application of various quantitative functional magnetic resonance imaging (fMRI) approaches at ultra-high magnetic field including the assessment with regards to applicability and reproducibility. Functional MRI (fMRI) commonly uses the blood oxygenation level dependent (BOLD) contrast to detect functionally induced changes in the oxy-deoxyhaemoglobin composition of blood which reflect cerebral neural activity. As these blood oxygenation changes do not only occur at the activation site but also downstream in the draining veins, the spatial specificity of the BOLD signal is limited. Therefore, the focus has moved towards more quantitative fMRI approaches such as arterial spin labelling (ASL), vascular space occupancy (VASO) or calibrated fMRI which measure quantifiable physiologically and physically relevant parameters such as cerebral blood flow (CBF), cerebral blood volume (CBV) or cerebral metabolic rate of oxygen (CMRO2), respectively. In this thesis a novel MRI technique was introduced which allowed the simultaneous acquisition of multiple physiological parameters in order to beneficially utilise their spatial and temporal characteristics. The advantages of ultra-high magnetic field were utilised to achieve higher signal-to-noise and contrast-to-noise ratios compared to lower field strengths. This technique was successfully used to study the spatial and temporal characteristics of CBV, CBF and BOLD in the visual cortex. This technique is the first one that allows simultaneous acquisition of CBV, CBF and BOLD weighted fMRI signals in the human brain at 7 Tesla. Additionally, this thesis presented a calibrated fMRI technique which allowed the quantitative estimation of changes in cerebral oxygen metabolism at ultra-high field. CMRO2 reflects the amount of thermodynamic work due to neural activity and is therefore a significant physical measure in neuroscience. The calibrated fMRI approach presented in this thesis was optimised for the use at ultra-high field by adjusting the MRI parameters as well as implementing a specifically designed radio-frequency (RF) pulse. A biophysical model was used to calibrate the fMRI data based on the simultaneous acquisition of BOLD and CBF weighted MRI signals during a gas-breathing challenge. The reproducibility was assessed across multiple brain regions and compared to that of various physiologically relevant parameters. The results indicate that the degree of intra-subject variation for calibrated fMRI is lower than for the classic BOLD contrast or ASL. Consequently, calibrated fMRI is a viable alternative to classic fMRI contrasts with regards to spatial specificity as well as functional reproducibility. This calibrated fMRI approach was also compared to a novel direct calibration technique which relies on complete venous oxygenation saturation during the calibration scan via a gas-breathing challenge. This thesis introduced several reliable quantitative fMRI approaches at 7 Tesla and the results presented are a step forward to the wider application of quantitative fMRI.:1 Introduction 3 2 Background to Functional Magnetic Resonance Imaging 7 2.1 Magnetic Resonance 7 2.1.1 Quantum Mechanics 7 2.1.2 The Classical Point of View 10 2.1.3 Radio Frequency Pulses 12 2.1.4 Relaxation Effects 13 2.1.5 The Bloch Equations 15 2.2 Magnetic Resonance Imaging 16 2.2.1 Data Acquisition 16 2.2.2 Image Formation 17 2.2.2.1 Slice Selection 17 2.2.2.2 Frequency Encoding 18 2.2.2.3 Phase Encoding 19 2.2.2.4 Mathematics of Image Formation 20 2.2.2.5 Signal Formation 22 2.3 Advanced Imaging Methods 24 2.3.1 Echo-Planar Imaging (EPI) 24 2.3.2 Partial Fourier Acquisition 25 2.3.3 Generalised Autocalibrating Partially Parallel Acquisition (GRAPPA) 25 2.3.4 Inversion Recovery (IR) 26 2.3.5 Adiabatic Inversion 26 2.3.5.1 Hyperbolic Secant (HS) RF pulses 28 2.3.5.2 Time Resampled Frequency Offset Corrected Inversion (tr-FOCI) RF Pulses 28 2.4 Physiological Background 29 2.4.1 Neuronal Activity 30 2.4.2 Energy Metabolism 31 2.4.3 Physiological Changes During Brain Activation 32 2.4.4 The BOLD Contrast 34 2.4.5 Disadvantages of the BOLD Contrast 35 2.5 Arterial Spin Labelling (ASL) 35 2.5.1 Pulsed Arterial Spin Labelling 37 2.5.2 Arterial Spin Labelling at Ultra-High Field 41 2.6 Vascular Space Occupancy (VASO) 42 2.6.1 VASO at Ultra-High Field 44 2.6.2 Slice-Saturation Slab-Inversion (SS-SI) VASO 45 2.7 Calibrated Functional Magnetic Resonance Imaging 47 2.7.1 The Davis Model 47 2.7.2 The Chiarelli Model 50 2.7.3 The Generalised Calibration Model (GCM) 52 3 Materials and Methods 53 3.1 Scanner Setup 53 3.2 Gas Delivery and Physiological Monitoring System 53 3.3 MRI Sequence Developments 55 3.3.1 Tr-FOCI Adiabatic Inversion 55 3.3.2 Optimisation of the PASL FAIR QUIPSSII Sequence Parameters 60 3.3.3 Multi-TE Multi-TI EPI 64 4 Experiment I: Comparison of Direct and Modelled fMRI Calibration 68 4.1 Background Information 68 4.2 Methods 69 4.2.1 Experimental Design 69 4.2.2 Visuo-Motor Task 70 4.2.3 Gas Manipulations 71 4.2.4 Scanning Parameters 71 4.2.5 Data Analysis 72 4.2.6 M-value Modelling 72 4.2.7 Direct M-Value Estimation 73 4.3 Results 74 4.4 Discussion 79 4.4.1 M-value Estimation 79 4.4.2 BOLD Time Courses 82 4.4.3 M-Maps and Single Subject Analysis 82 4.4.4 Effects on CMRO2 Estimation 83 4.4.5 Technical Limitations and Implications for Calibrated fMRI 84 4.5 Conclusion 89 5 Experiment II: Reproducibility of BOLD, ASL and Calibrated fMRI 90 5.1 Background Information 90 5.2 Methods 91 5.2.1 Experimental Design 91 5.2.2 Data Analysis 91 5.2.3 Reproducibility 93 5.2.4 Learning and Habituation Effects 95 5.3 Results 95 5.4 Discussion 101 5.4.1 Breathing Manipulations 102 5.4.2 Functional Reproducibility 107 5.4.3 Habituation Effects on Reproducibility 109 5.4.4 Technical Considerations for Calibrated fMRI 110 5.5 Conclusion 112 6 Experiment III: Simultaneous Acquisition of BOLD, ASL and VASO Signals 113 6.1 Background Information 113 6.2 Methods 114 6.2.1 SS-SI VASO Signal Acquisition 114 6.2.2 ASL and BOLD Signal Acquisition 114 6.2.3 Experimental Design 114 6.2.4 Data Analysis 115 6.3 Results 115 6.4 Discussion 116 6.5 Conclusion 120 7 Conclusion and Outlook 12

A Non-cognitive Behavioral Model for Interpreting Functional Neuroimaging Studies

The dominant model for interpreting brain imaging experiments, which we refer to as the Standard Cognitive Model (SCM), assumes that the brain is organized in support of mental processes that control behavior. However, functional neuroimaging experiments of cognitive tasks have not shown clear anatomic segregation between mental processes originally proposed by this model. This failing has been blamed on limitations in imaging technology and non-linearity in the brain’s implementation of these processes. However, the validity of the underlying cognitive models used to describe the brain has rarely been questioned or directly tested against imaging results. We propose an alternative model of brain function, that we term the Non-cognitive Behavioral Model (NBM), which correlates observed human behavior directly with measured brain activity without making assumptions about intervening cognitive processes. Our model derives from behavioral psychology but is extended to include brain activity, in addition to behavior, as observables. A further extension is the role of neuroplasticity, as opposed to innate cognitive processes, in developing the brain’s support of cognitive behavior. We present the theoretical basis with which the SCM maps cognitive processes onto functional magnetic resonance and positron emission tomography images and compare and contrast with the NBM. We also describe how the NBM can be used experimentally to study how the brain supports behavior. Two applications are presented that support the usefulness of the NBM. In one, the NBM use of the total functional imaging signal (not just the differences between states) provides a stronger correlation of neural activity with the behavioral state of consciousness than the SCM approach in both anesthesia and coma. The second example reviews studies of facial and object recognition that provide evidence for the NBM proposal that neuroplasticity and experience play key roles in the brain’s support of recognition and other behaviors. The conclusions regarding neuroplasticity are then generalized to explain the incomplete functional segregation observed in the application of the SCM to neuroimaging

Interação entre as áreas funcionais do sistema visual e do sistema vestibular: estudo com RMF e EGV

The static body equilibrium is controlled by three sensory systems: the vestibular system, responsible for informing the position and the movements of the head; the visual system, which informs the spatial objects position relative to the body; and the proprioceptive system, which controls posture and body movements. These three systems must always work in harmony, otherwise the individual will present balance problems. Thus, it is important to characterize the cortical regions, as well as their interactions, involved in this process. For this it is necessary to use functional neuroimaging techniques, the functional magnetic resonance imaging (fMRI) is one of the most used techniques in this field nowadays. However, a large fMRI experiments require the use of electronic devices for producing somatosensory stimulation in the human body, where the main difficulty is its hostile environment for electronic circuits. The galvanic vestibular stimulation is one of the most used methods to stimulate the vestibular system. This stimulation consist of applying a low current amplitude directly on vestibular afferents, which acts firing the primary vestibular neurons, affecting the otolithic afferents and the semicircular canals fibers. The objective of this work is to evaluate and analyze the brain areas involved with visual and galvanic vestibular stimulations and their interactions using fMRI. Therefore, as a first step of this research, a galvanic vestibular stimulator was validated in vivo. The electrical stimulator did not interfere in a significance way on magnetic resonance images quality and could be safely used in fMRI experiments. Tests were performed to select an electrode sufficiently comfortable for the volunteer during the galvanic vestibular stimulation and that do not cause artifacts in the images. After completed these steps, 24 subjects were selected to perform three tasks: a purely visual (a flashing checkerboard in the center of the screen), a purely vestibular (with application of galvanic vestibular stimulation) and a simultaneous, presenting the visual and vestibular stimuli together. The purely visual stimulation showed activation of the primary and associative visual cortices, while the purely vestibular stimulation led to activation of areas involved in multimodal function of the vestibular system, such as the parieto-insular vestibular cortex, the inferior parietal lobe, the superior temporal gyrus, the precentral gyrus and the cerebellum. The simultaneous stimulation of visual and vestibular systems resulted in activation of the middle and inferior frontal gyri. In addition to the reciprocal inhibitory visualvestibular interaction pattern had been more evident during the simultaneous condition, it was observed that frontal regions (dorsomedial prefrontal cortex and superior frontal gyrus) are involved with the executive function processing when there is conflicting information of visual and vestibular systems.CAPES, CNPqO equilíbrio estático corporal é comandado por três sistemas sensoriais: o sistema vestibular, responsável pelas informações sobre a posição e os movimentos da cabeça; o sistema visual, que informa a posição espacial dos objetos em relação ao nosso corpo; e o sistema proprioceptivo, que controla a postura e a movimentação corporal. Estes três sistemas devem funcionar sempre em sintonia, caso contrário, o indivíduo apresentará problemas de equilíbrio. Dessa forma, é importante caracterizar as regiões corticais, bem como suas interações, envolvidas neste processo. Para isto, é necessário a utilização de técnicas de neuroimagem funcional, sendo a ressonância magnética funcional (RMf) uma das técnicas mais utilizadas neste campo nos dias de hoje. Entretanto, uma grande parte dos experimentos de RMf requer o uso de aparelhos eletrônicos para produzir estimulações somatosensoriais no corpo humano, onde a principal dificuldade é o seu ambiente hostil aos circuitos eletrônicos. A estimulação galvânica vestibular é um dos métodos mais utilizados para estimular o sistema vestibular. Esta consiste em fornecer uma corrente de baixa amplitude diretamente nas aferências vestibulares, a qual atua no disparo dos neurônios vestibulares primários atingindo principalmente as aferências otolíticas e as fibras dos canais semicirculares. O objetivo deste trabalho é analisar e avaliar as áreas cerebrais envolvidas com as estimulações visual e galvânica vestibular e suas interações, utilizando a técnica de RMf e um estimulador galvânico vestibular. Para tanto, como primeira etapa desta pesquisa, validou-se in vivo um estimulador galvânico vestibular. O estimulador elétrico não interferiu de forma significativa na qualidade das imagens de ressonância magnética e pode ser utilizado com segurança nos experimentos de RMf. Testes foram realizados para determinar um eletrodo suficientemente confortável para o voluntário durante a estimulação galvânica vestibular e que não causasse artefato nas imagens. Após estas etapas concluídas, 24 voluntários foram selecionados para realizarem três tarefas: uma puramente visual (um tabuleiro de xadrez piscante no centro da tela), uma puramente vestibular (pela aplicação da estimulação galvânica vestibular) e uma simultânea, com a apresentação em conjunto dos estímulos visual e vestibular. A estimulação puramente visual mostrou ativação dos córtices visual primário e associativo, enquanto que a estimulação puramente vestibular levou a ativação das principais áreas envolvidas com a função multimodal do sistema vestibular, como o córtex parietoinsular vestibular, o lóbulo parietal inferior, o giro temporal superior, o giro pré-central e o cerebelo. A estimulação simultânea dos sistemas visual e vestibular resultou na ativação dos giros frontal médio e inferior. Além do padrão de interação visual-vestibular inibitório recíproco ter sido mais evidente durante a condição simultânea, observou-se que as regiões frontais (córtex dorsomedial pré-frontal e giro frontal superior) estão envolvidas com o processamento da função executiva quando existem informações conflitantes dos sistemas visual e vestibular