Dr. Danilov is Senior Scientist in the Orthopedics and Rehabilitation Medicine Department, University of Wisconsin School of Medicine and Public Health. He is a neuroscientist with over 30 years experience in research on brain function and the special senses, including vision, taste, and balance. His primary interest areas include neuroplasticity, neurorehabilitation, and sensory systems physiology. Dr. Danilov led the discovery of the balance retention effect, the development of specific training regimens, and the ongoing identification of potential clinical and non-clinical applications of neuromodulation and sensory substitution technology.
Abnormal muscle activation patterns are associated with chronic gait deficits following traumatic brain injury
Gait Posture. 2018 May;62:510-517. doi: 10.1016/j.gaitpost.2018.04.012. Epub 2018 Apr 12.
BACKGROUND: Gait and balance disorders are common among individuals who have experienced a mild to moderate traumatic brain injury (TBI). However, little is known about how the neuromuscular control of gait is altered following a TBI.
RESEARCH QUESTION: Investigate the relationship between lower limb muscle activation patterns and chronic gait deficits in individuals who previously experienced a mild to moderate TBI.
METHODS: Lower extremity electromyographic (EMG) signals were collected bilaterally during treadmill and overground walking in 44 ambulatory individuals with a TBI >1 year prior and 20 unimpaired controls. Activation patterns of TBI muscles were cross-correlated with normative data from control subjects to assess temporal phasing of muscle recruitment. Clinical assessments of gait and balance were performed using dynamic posturography, the dynamic gait index, six-minute walk test, and preferred walking speed.
RESULTS: TBI subjects exhibited abnormal activation patterns in the tibialis anterior, medial gastrocnemius, and rectus femoris muscles during both overground and treadmill walking. Activation patterns of the vastus lateralis and soleus muscles did not differ from normal. There was considerable heterogeneity in performance on clinical balance and gait assessments. Abnormal muscle activation patterns were significantly correlated with variations in the dynamic gait index among the TBI subjects.
SIGNIFICANCE: Individuals who have experienced a prior TBI do exhibit characteristic changes in the temporal coordination of select lower extremity muscles, which may contribute to impairments during challenging walking tasks.
Non-invasive neuromodulation to improve gait in chronic multiple sclerosis: a randomized double blind controlled pilot trial
J Neuroeng Rehabil. 2014 May 1;11:79. doi: 10.1186/1743-0003-11-79.
BACKGROUND: This study sought to examine the effect of targeted physical therapy with and without cranial nerve non-invasive neuromodulation (CN-NINM), on the walking ability of people with MS who exhibited a dysfunctional gait. We hypothesized that subjects who received electrical stimulation would have greater improvement than those who had a control device after a 14-week intervention. Gait disturbance is a common problem for people with multiple sclerosis (MS). Current management may include exercise, pharmacology, functional electrical stimulation, compensatory strategies, use of assistive devices, and implanted electrical devices. We have developed an effective rehabilitative strategy using neuromodulation of the cranial nerves via electrical stimulation of the tongue to enhance the plasticity of the brain.
METHODS: The study is a within-subject blinded randomized control design. Twenty chronic MS subjects with an identified gait disturbance were assigned to either an active or control group. Both groups completed a 14-week intervention program using a standardized combination of exercise and a device that provided electrical stimulation to the tongue. Those in the active group received electrical stimulation on the tongue that they could perceive. Those in the control group used a device that did not provide a physiologically significant stimulus and was not perceivable. Subjects were assessed with the Dynamic Gait Index (DGI).
RESULTS: The DGI scores improved for both groups. There were significant between-group differences, with the active group showing statistically greater improvement than the control group mean.
CONCLUSION: People with MS demonstrated improved gait with CN-NINM training in a pilot randomized controlled trial. This study suggests that tongue-based neurostimulation may amplify the benefits of exercise for improving gait in people with chronic MS.
Altered connectivity of the balance processing network after tongue stimulation in balance-impaired individuals
Brain Connect. 2013;3(1):87-97. doi: 10.1089/brain.2012.0123.
Some individuals with balance impairment have hypersensitivity of the motion-sensitive visual cortices (hMT+) compared to healthy controls. Previous work showed that electrical tongue stimulation can reduce the exaggerated postural sway induced by optic flow in this subject population and decrease the hypersensitive response of hMT+. Additionally, a region within the brainstem (BS), likely containing the vestibular and trigeminal nuclei, showed increased optic flow-induced activity after tongue stimulation. The aim of this study was to understand how the modulation induced by tongue stimulation affects the balance-processing network as a whole and how modulation of BS structures can influence cortical activity. Four volumes of interest, discovered in a general linear model analysis, constitute major contributors to the balance-processing network. These regions were entered into a dynamic causal modeling analysis to map the network and measure any connection or topology changes due to the stimulation. Balance-impaired individuals had downregulated response of the primary visual cortex (V1) to visual stimuli but upregulated modulation of the connection between V1 and hMT+ by visual motion compared to healthy controls (p ≤ 1E-5). This upregulation was decreased to near-normal levels after stimulation. Additionally, the region within the BS showed increased response to visual motion after stimulation compared to both prestimulation and controls. Stimulation to the tongue enters the central nervous system at the BS but likely propagates to the cortex through supramodal information transfer. We present a model to explain these brain responses that utilizes an anatomically present, but functionally dormant pathway of information flow within the processing network.
Electrical tongue stimulation normalizes activity within the motion-sensitive brain network in balance-impaired subjects as revealed by group independent component analysis
Brain Connect. 2011;1(3):255-65. doi: 10.1089/brain.2011.0029. Epub 2011 Sep 12.
Multivariate analysis of functional magnetic resonance imaging (fMRI) data allows investigations into network behavior beyond simple activations of individual regions. We apply group independent component analysis to fMRI data collected in a previous study looking at the sustained neuromodulatory effects of electrical tongue stimulation in balance-impaired individuals. Twelve subjects with balance disorders viewed optic flow in an fMRI scanner before and after 5 days of electrical tongue stimulation. Nine healthy controls also viewed the visual stimuli but did not receive any stimulation. Multiple regression of the 47 estimated components found two that were modulated by the visual stimuli. Component 7, comprised primarily of the primary visual cortex (V1), responded to all visual stimuli and showed no difference in task-related activity between the healthy controls and the balance-impaired subjects before or after stimulation. Component 11 responded only to motion in the visual field and contained multiple cortical and subcortical regions involved in processing information pertinent to balance. Two-sample t-tests of the calculated signal change revealed that the task-related activity of this network is greater in balance-impaired subjects compared with controls before stimulation (p=0.02), but that this network hypersensitivity decreases after electrical tongue stimulation (p=0.001).
High-resolution fMRI detects neuromodulation of individual brainstem nuclei by electrical tongue stimulation in balance-impaired individuals
Neuroimage. 2011 Jun 15;56(4):2129-37. doi: 10.1016/j.neuroimage.2011.03.074. Epub 2011 Apr 8.
High-resolution functional magnetic resonance imaging (fMRI) can be used to precisely identify blood oxygen level dependent (BOLD) activation of small structures within the brainstem not accessible with standard fMRI. A previous study identified a region within the pons exhibiting sustained neuromodulation due to electrical tongue stimulation, but was unable to precisely identify the neuronal structure involved. For this study, high-resolution images of neural activity induced by optic flow were acquired in nine healthy controls and nine individuals with balance dysfunction before and after information-free tongue stimulation. Subjects viewed optic flow videos to activate the structures of interest. Sub-millimeter in-plane voxels of structures within the posterior fossa were acquired using a restricted field of view. Whole-brain functional imaging verified that global activation patterns due to optic flow were consistent with previous studies. Optic flow activated the visual association cortices, the vestibular nuclei, and the superior colliculus, as well as multiple regions within the cerebellum. The anterior cingulate cortex showed decreased activity after stimulation, while a region within the pons had increased post-stimulation activity. These observations suggest the pontine region is the trigeminal nucleus and that tongue stimulation interfaces with the balance-processing network within the pons. This high-resolution imaging allows detection of activity within individual brainstem nuclei not possible using standard resolution imaging.
Sustained cortical and subcortical neuromodulation induced by electrical tongue stimulation
Brain Imaging Behav. 2010 Dec;4(3-4):199-211. doi: 10.1007/s11682-010-9099-7.
This pilot study aimed to show that information-free stimulation of the tongue can improve behavioral measures and induce sustained neuromodulation of the balance-processing network in individuals with balance dysfunction. Twelve balance-impaired subjects received one week of cranial nerve non-invasive neuromodulation (CN-NINM). Before and after the week of stimulation, postural sway and fMRI activation were measured to monitor susceptibility to optic flow. Nine normal controls also underwent the postural sway and fMRI tests but did not receive CN-NINM. Results showed that before CN-NINM balance-impaired subjects swayed more than normal controls as expected (p ≤ 0.05), and that overall sway and susceptibility to optic flow decreased after CN-NINM (p ≤ 0.005 & p ≤ 0.05). fMRI showed upregulation of visual sensitivity to optic flow in balance-impaired subjects that decreased after CN-NINM. A region of interest analysis indicated that CN-NINM may induce neuromodulation by increasing activity within the dorsal pons (p ≤ 0.01).
VEP and PERG acuity in anesthetized young adult rhesus monkeys
Visual neuroscience, 16(4), pp.607-617.