Lab for Clinical &

Integrative Neuroscience

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Tinnitus

Tinnitus is defined as the perception of sound, typically tones and/or noise, in the absence of a corresponding external source. Our research covers all aspects of tinnitus in humans, with a specific focus on using neuroimaging methods to study its underlying mechanisms. Ongoing projects include studies of network-level function, the differences between acute and chronic tinnitus, dynamic systems theory, mechanisms of action in therapeutic measures, and genetic imaging.

• Resting-state functional connectivity

Chronic tinnitus is a disorder that cannot be simply characterized as a result of sensory loss. Our previous studies on cortical thickness and white matter fiber changes showed that aging and hearing loss are main factors in structural degenerations in chronic tinnitus patients. In this project, we utilize graph theory measures on wavelet-transformed time series of resting-state fMRI signals, hoping to systematically understand how top-down compensatory or noise-cancellation mechanisms are organized in the functional connectome. In addition, network measures are correlated to tinnitus-related subjective measures such as distress or perceived loudness level in order to analyze the differences between individual systems.

• Task-based fMRI

Brain disorders feature activity distributed across segregated systems at a network level. This implies that disorders with different symptomatic profiles have similar pathological mechanisms, e.g. through interactions with affect, reward, and/or learning systems. We test this using a task-based fMRI experiment to examine the brains of patients with chronic, distressful tinnitus. By presenting these patients with auditory stimuli, both at their tinnitus percept frequency and at a control frequency, we analyze the resulting connectivity profiles and compare patients according to their reported levels of distress and percept loudness.

• Auditory evoked potentials

In order to process information efficiently, the brain uses learning and memory to predict environmental stimuli and then encodes only those aspects of incoming signals that deviate from its predictions. When sensory deafferentation occurs, the missing information constitutes a persistent prediction error that the brain treats as salient. Phantom perception supposedly results from the brain using compensatory mechanisms to resolve this error, i.e. by filling in the gap. In the case of hearing loss, the resulting phantom is called tinnitus. This project investigates this error-resolution hypothesis by analyzing auditory evoked potentials in a cohort of young and near-normal hearing tinnitus patients compared to an age- and gender-matched control group.

• The Zwicker illusion

Most human studies of tinnitus focus on its chronic stage, largely because induction of acute tinnitus would require exposure to high-intensity sounds and thus risk hearing loss. The neural correlates of acute tinnitus are nevertheless important to understanding its pathology. However it is possible to safely induce a percept that is a proxy for acute tinnitus known as the Zwicker illusion. This illusion is created by presenting white noise with a notch (i.e. narrow band-stop filter) at specific frequencies followed immediately by a period of silence. During this silent period, most adults will briefly perceive sound at the missing notch frequencies. We use EEG to study the neural correlates of the Zwicker illusion as a proxy for acute tinnitus.

• Thalamocortical dysrhythmia

There is no known cure for tinnitus. In extreme cases, however, direct stimulation of auditory cortex using surgically implanted electrodes can be an effective therapeutic measure. We examine a small group of tinnitus patients who have been implanted in this way. By recording behavioral data and by using the implanted electrode array to record EEG signals directly from cortex before, during, and after stimulation, we can determine whether the therapy works and how. We hypothesize that the physiological mechanism of action is described by the thalamocortical dysrhythmia model.

• Nonlinear brain dynamics

A core principle of brain function is the ability to dynamically adapt to the environment by transitioning between different states, which is achieved in part through learning which circumstances are likely to reoccur. Current hypotheses suggest that chronic neuropathology represents the brain learning a state in the same way that normative function does. If true, then pathological states are treated by the brain as the new “normal,” which would explain why treatment is often so difficult. This project therefore aims to test this hypothesis in tinnitus. Specifically, we investigate the changes in nonlinear brain dynamics to assess the state of tinnitus patients compared to that of healthy controls.

• Genetic imaging

The investigation of the underlying molecular aspects contributing to variations in tinnitus intensity and tinnitus-related distress is rather new; however, research has shown that psychological and behavioral factors can heighten the intensity of tinnitus.  Tinnitus distress symptoms are characterized by increased activity in a brain network that involves regions that also exhibit variations of molecular activity. This suggests that the examination of the underlying molecular mechanisms might become necessary for the successful monitoring of tinnitus distress. In this study, we consider the association between pathophysiological alterations of genetic markers in relation to tinnitus distress. This study will facilitate a close examination of the molecular and neural brain dynamics related to tinnitus distress in chronic tinnitus patients, which we hope will offer new insights regarding the underlying mechanisms of tinnitus and contribute to the development of individualized treatment options.

 

Enhancing Learning and Memory

Mastery of difficult skills including learning a foreign language typically requires hours of practice. Studies suggest that invasive and non-invasive neuromodulation can accelerate learning and therefore improve memory when paired with training. In a series of studies in healthy subjects as well as patient populations, we investigate novel approaches to improve learning and memory by pairing training with vagus nerve stimulation (VNS), which is invasive, or transcranial direct current stimulation (tDCS), which is noninvasive. We also collect data from auditory evoked potentials, pupillometry, cortisol, and salivary alpha-amylase both before and after stimulation to further investigate the mechanisms underlying each neuromodulation technique.

• Study 1: Language task paired with VNS

• Study 2: Language task paired with tDCS

• Study 3: Face-recognition task paired with tDCS

• Study 4: Investigating the underlying mechanism of neuromodulation in accelerated learning

 

Pain

Occipital Nerve Stimulation (ONS) is a technique that is established as a treatment for pain that can be applied invasively (implanted electrodes) as well as non-invasively (transcranial Direct Current Stimulation). In a series of studies we aim to investigate (1) whether repeated ONS can suppress pain symptoms in patient populations, (2) the mechanism of action in ONS using [15O] H2O PET, and (3) which networks are specifically affected by ONS using fMRI.

• Gulf War Illness

Gulf War Illness is a chronic and multisymptomatic disorder affecting returning military veterans of the 1990-1991 Gulf War; pain is both a major complaint and a leading cause of disability in veterans with this illness. This study aims to investigate whether repeated occipital nerve stimulation can produce long-term modulation of pain pathways leading to suppression of pain symptoms in Gulf War Illness patients.

• Fibromyalgia

Recent studies have shown that ONS is an effective treatment in suppressing pain for fibromyalgia patients. However, the mechanism of action for this pain suppression is not yet known. In this study, we collect static [15O] H2O PET scans of fibromyalgia patients implanted with electrodes. By analyzing these PET images, we aim to discover the mechanism of action for ONS-mediated pain suppression in fibromyalgia patients.

• ONS-driven changes in functional connectivity

Despite featuring no direct connections to cerebral cortex, the occipital nerve is interconnected with other nerves and forms a continuous network with the trigeminocervical nucleus caudalis and the cervical horn at the C1 and C2 levels. Through this so-called trigeminocervical complex, stimulation of the occipital nerve can affect cortical networks involved in pain processing and other functions. We use fMRI to measure the effects of occipital nerve stimulation in patients with chronic pain compared with healthy controls. By examining functional connectivity, we aim to learn which networks are specifically affected by stimulation.

 

Mild Cognitive Impairment

Mild Cognitive Impairment (MCI) commonly represents the 'at-risk' state of developing Alzheimer's disease. The limited effectiveness of pharmacological treatments for cognitive impairment has led to an increased interest on alternative treatment options. This project investigates the potential of transcranial direct current stimulation as a treatment to improve and stabilize cognitive impairment in MCI patients using behavioral, electrophysiological, and resting-state functional magnetic resonance imaging data to assess short- and long-term outcomes.

 

Aging

Static functional brain connectivity is known to change as a result of the normal aging process. What is yet unknown is how aging alters dynamic functional connectivity, i.e. changes in connectivity over short time-scales. Using large electrophysiological datasets, we evaluate dynamic functional connectivity in healthy people of all ages. By comparing results across age groups, we determine whether changes occur as a result of age and, if so, where those changes are localized in the brain. We demonstrate not only the changes in functional connectivity within the brain but also individual levels of brain-state dynamicity.

 

Simultaneous Measurement of tDCS and fMRI

Transcranial direct current stimulation (tDCS) is a widely studied technique for noninvasive neuromodulation. By applying a weak electrical current to specific parts of the head, tDCS can deliver excitatory or inhibitory signals to specific brain regions. However, it is not yet known how tDCS specifically changes the brain to elicit microscopic to macroscopic changes. We use MRI-compatible tDCS devices to measure these changes both during and after stimulation. This study will be the first to directly examine real-time changes induced by tDCS using fMRI.

 

Allostasis as a General Model of Brain Function

Allostasis, an update to the classic theory of homeostasis, is based on the principle that efficient adaptation to the environment requires a predictive model to meet demands proactively. This framework thus provides an evolutionary basis with which to unite the various lines of research on the predictive brain. We explore this idea here, arguing that improving predicted fitness is the goal of brain function in general. We further demonstrate how this perspective enables a unifying account of both normative and pathological function. Finally, we generate hypotheses based on these arguments and on the neuroimaging literature to encourage integrative approaches to future research.

 

Lab for Clinical & Integrative Neuroscience, School of Behavioral and Brain Sciences, University of Texas at Dallas © 2017