George Wittenberg | University of Pittsburgh (original) (raw)

Papers by George Wittenberg

Experimental Brain Research, 2022

Reaching for an object in space forms the basis for many activities of daily living and is import... more Reaching for an object in space forms the basis for many activities of daily living and is important in rehabilitation after stroke and in other neurological and orthopedic conditions. It has been the object of motor control and neuroscience research for over a century, but studies often constrain movement to eliminate the effect of gravity or reduce the degrees of freedom. In some studies, aging has been shown to reduce target accuracy, with a mechanism suggested to be impaired corrective movements. We sought to explore how such changes in accuracy relate to changes in finger, shoulder and elbow movements during performance of reaching movements with the normal effects of gravity, unconstrained hand movement, and stable target locations. Three-dimensional kinematic data and electromyography were collected in 14 young (25 ± 6 years) and 10 older adults (68 ± 3 years) during second-long reaches to 3 targets aligned vertically in front of the participants. Older adults took longer to initiate a movement than the young adults and were more variable and inaccurate in their initial and final movements. Target height had greater effect on trajectory curvature variability in older than young adults, with angle variability relative to target position being greater in older adults around the time of peak speed. There were significant age-related differences in use of the multiple degrees of freedom of the upper extremity, with less variability in shoulder abduction in the older group. Muscle activation patterns were similar, except for a higher biceps-triceps co-contraction and tonic levels of some proximal muscle activation. These results show an age-related deficit in the motor planning and online correction of reaching movements against a predictable force (i.e., gravity) when it is not compensated by mechanical support.

Stroke, 2012

Introduction: Intensive task practice assisted by robots is a promising treatment for hemiparesis... more Introduction: Intensive task practice assisted by robots is a promising treatment for hemiparesis after stroke. However, not all respond to the treatment, so a better patient selection method is needed. Previous studies have shown that motor cortical responsiveness to transcranial magnetic stimulation (TMS) may predict gains from practice and may change with those gains. Hypotheses: In the first study, we hypothesized that more intact motor cortical pathways would predict better response to treatment, and that motor cortical excitability would increase when motor function improved. In the second study we had the same hypotheses, and: Motor cortical excitability would increase during a single session of intensive therapy, and that this increase would itself predict gains in motor function. Methods: Study 1: participants in trials of upper extremity robotic rehabilitation in chronic stroke were recruited to have TMS measures for extensor digitorum communis (EDC) and biceps muscles bef...

Stroke, 2018

Associations between subcortical gray matter volume and motor performance post-stroke are unclear... more Associations between subcortical gray matter volume and motor performance post-stroke are unclear, partly because many stroke MRI studies are underpowered. Potential influences of the severity of motor impairment, lesion laterality, and time since stroke on these associations is also unknown. Here, we addressed these questions using a large dataset (n=629) from the ENIGMA Stroke Recovery working group (http://enigma.usc.edu). Regression analyses examined brain volumes as predictors of motor scores. ENIGMA FreeSurfer protocols extracted volumes from 16 subcortical regions on T1-weighted MRIs; segmentations were manually quality controlled. Motor scores were calculated as a percentage of the maximum possible score (100% = no impairment). Covariates (e.g., age, sex, intracranial volume) were modeled. Statistical significance was assessed nonparametrically by permutation. Separate analyses were performed, stratifying by motor severity and time since stroke. Each analysis was also subdiv...

Journal of Neurophysiology, 1992

1. To understand how a multisegmental animal coordinates motor activity over more than one segmen... more 1. To understand how a multisegmental animal coordinates motor activity over more than one segment, we studied shortening behavior in the medicinal leech, in which several segments contract longitudinally in response to a moderately strong mechanical stimulus. 2. We first demonstrated that the neuronal activity responsible for shortening behavior occurred in semi-intact and isolated nerve cord preparations, and then characterized the responses of motor neurons in isolated preparations. The motor output during shortening was simultaneous excitation of motor neurons innervating dorsal longitudinal muscle and of motor neurons innervating ventral longitudinal muscle. 3. The stronger the stimulus, the more segments produced the shortening motor output, with the segments nearest the stimulus recruited first. 4. Although the shortening response was produced in several segments near the site of stimulation, it was never produced in the stimulated segment, where the local bending motor outpu...

Biological Psychiatry, 2018

Background: The inhibitory deficits in the motor cortex in schizophrenia have been well demonstra... more Background: The inhibitory deficits in the motor cortex in schizophrenia have been well demonstrated using short-interval intracortical inhibition (SICI) by transcranial magnetic stimulation (TMS). However, it remains unknown whether these deficits originate from dysfunction of motor cortex itself or reflect abnormal modulations of the motor cortex by other schizophrenia-related brain areas. Methods: Twenty-four patients with schizophrenia spectrum disorders and 30 healthy controls completed the study. SICI was obtained by delivering TMS over the left motor cortex. Restingstate functional magnetic resonance imaging and diffusion tensor imaging fractional anisotropy were used to measure functional connectivity (FC) and white matter microstructures, respectively. Stimulation sites for SICI at the motor cortex were used as the seeds to obtain the whole-brain FC maps. The clinical symptoms were assessed with Brief Psychiatric Rating Scale (BPRS). Results: In schizophrenia, left prefrontal cortex (PFC)-motor cortex FC was inversely associated with SICI but positively associated with the underlying white matter microstructure at the left corona radiata (CR), and also associated with overall symptoms (all corrected p<0.05). Mediation analysis showed that the PFC-motor cortex FC significantly mediates the corona radiata white matter effects on SICI (p=0.007). Conclusions: Higher resting-state left PFC-motor cortex functional connectivity, accompanied by a higher FA of left corona radiata, predicts less inhibitory deficits, suggesting the inhibitory deficits in the motor cortex in schizophrenia may in part be mediated by a top-down prefrontal influence. SICI may serve as a robust biomarker indexing inhibitory dysfunction at anatomic as well as circuitry levels in schizophrenia.

Cerebellum (London, England), Jan 15, 2018

Cerebellar-prefrontal connectivity has been recognized as important for behaviors ranging from mo... more Cerebellar-prefrontal connectivity has been recognized as important for behaviors ranging from motor coordination to cognition. Many of these behaviors are known to involve excitatory or inhibitory modulations from the prefrontal cortex. We used cerebellar transcranial magnetic stimulation (TMS) with simultaneous electroencephalography (EEG) to probe cerebellar-evoked electrical activity in prefrontal cortical areas and used magnetic resonance spectroscopy (MRS) measures of prefrontal GABA and glutamate levels to determine if they are correlated with those potentials. Cerebellar-evoked bilateral prefrontal synchrony in the theta to gamma frequency range showed patterns that reflect strong GABAergic inhibitory function (r = - 0.66, p = 0.002). Stimulation of prefrontal areas evoked bilateral prefrontal synchrony in the theta to low beta frequency range that reflected, conversely, glutamatergic excitatory function (r = 0.66, p = 0.002) and GABAergic inhibitory function (r = - 0.65, p ...

Neurorehabilitation and Neural Repair, 2000

In recovered stroke patients, performance of motor tasks with the affected limb has been reported... more In recovered stroke patients, performance of motor tasks with the affected limb has been reported to activate cortical areas ipsilateral to the affected side. The better to determine the causal role these areas play in recovery of motor function, we assessed cerebral activation during motor activity longitudinally after hemiparesis due to cerebral infarction. A secondary goal was to ascertain the relation between mirror movements and activation ipsilateral to motor activity. Positron emission tomography with oxygen-15 water measured regional cerebral blood flow during wrist movement early and late in the course of recovery from hemiparesis. Surface electromyography recorded muscular activity, and computer-assisted video analysis quantified movement during the scans. Mirror movements, movements contralateral to the instructed movement of the hemiparetic arm, were often seen. Activation of motor areas in the hemisphere ipsilateral to the affected limb roughly correlated with presence ...

Neuroscience, 1999

The effect of the neurosteroid dehydroepiandrosterone sulfate on inhibitory synaptic transmission... more The effect of the neurosteroid dehydroepiandrosterone sulfate on inhibitory synaptic transmission was studied in area CA1 of the rat hippocampus using an in vitro hippocampal slice preparation. Synaptic responses elicited by stimulation of Schaffer collateral fibers were recorded extracellularly as population spikes in the somatic region and as synaptic field potentials in the dendritic region. Bath application of dehydroepiandrosterone sulfate (10 microM) enhanced the synaptically evoked somatic population spike with no effect on the dendritic synaptic potential. Isolation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor-mediated component of the synaptic response by addition of antagonists of N-methyl-D-aspartate and GABA receptors to the perfusion saline demonstrated that dehydroepiandrosterone sulfate had no effect on this component of the dendritic synaptic potential. In contrast, dehydroepiandrosterone sulfate antagonized GABA receptor-mediated inhibitory effects in the somatic region, resulting in an augmentation of the somatic population spike amplitude. Paired-pulse facilitation was unaltered by dehydroepiandrosterone sulfate, thus arguing against possible presynaptic sites of dehydroepiandrosterone sulfate's actions. These results indicate that dehydroepiandrosterone sulfate can alter synaptic transmission in the hippocampus through selective postsynaptic actions on inhibitory synaptic transmission. A synaptic effect of dehydroepiandrosterone sulfate is consistent with a neuromodulatory role for this neurosteroid in the central nervous system, and may contribute to the reported effects of dehydroepiandrosterone sulfate on cognitive processes such as learning and memory.

Neurorehabilitation and Neural Repair, 2007

Background. Recovery of motor function after stroke may be associated with changes in inhibitory ... more Background. Recovery of motor function after stroke may be associated with changes in inhibitory and facilitatory circuits within the motor cortex. Objective. We explored such changes longitudinally after stroke, using transcranial magnetic stimulation (TMS). Methods. Subjects ( N = 27) with a single cerebral infarction affecting movement of either hand were studied at <10 days poststroke, 1 month, and 6 months. Age-matched control subjects ( N = 9) were studied at 2 times. Results. In contrast to previous studies, paired-pulse inhibition was increased in patients with a subcortical stroke compared to control subjects. After a cortical stroke, paired-pulse facilitation was also increased. Stroke location affected the time course of inhibition. Subcortical stroke resulted in increased inhibition initially that decreased over time, whereas cortical stroke had no significant effect on inhibition and a more immediate and lasting effect on facilitation. Conclusions. The time course of...

Experientia, 1988

bution and partial characterization of FMRFamide-like peptides in the stomatogastric nervous syst... more bution and partial characterization of FMRFamide-like peptides in the stomatogastric nervous system of the rock crab, Cancer borealis and the spiny lobster, Panulirus interruptus.

Archives of Physical Medicine and Rehabilitation, 2010

Cycling with functional electrical stimulation (FES) is mainly used for people with spinal cord i... more Cycling with functional electrical stimulation (FES) is mainly used for people with spinal cord injury; however it has been applied to other populations. There are no reports of its benefits for adults with cerebral palsy (CP). Design: Mixed quantitative/qualitative case report. Setting: Home-based intervention. Patient: 49-year-old man with spastic diplegia classified as Gross Motor Functional Classification System Level II. Interventions: The participant cycled with FES to the quadriceps, plantarflexor, and gluteal muscles for 30 minutes, 3 times per week for 12 weeks. He volitionally cycled at his maximal resistance level and FES augmented his effort to allow more vigorous cycling. Main Outcome Measures: Data collected included gait spatiotemporal parameters, the Timed Up & Go (TUG), a 6-minute walk test (6MWT), isometric muscle strength, percent lean tissue, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), the Canadian Occupational Performance Measure (COPM), and qualitative semi-structured interviews. Results: TUG time decreased (11.9Ϯ0.4 to 9.0Ϯ0.8s), barefoot gait speed improved (111.8Ϯ8.3 to 120.7Ϯ4.3cm/s), and 6MWT distance increased by 20.1m. Strength improved in the quadriceps, hamstrings, and dorsiflexors, but declined for the plantarflexors. Percent lean tissue was unchanged. SF-36 scores improved (62.1 to 77.6), and he rated his COPM satisfaction and performance as improved for 4 of 5 goals. The participant reported greater ease of walking, "I'm not dragging my legs as much," and fewer falls. Contradictory to the improvements noted was the development of low back pain that the participant attributed to positioning during cycling. Conclusions: FES cycling may be effective in improving impairments that translate into improved function. Potential issues with cycle seating and design should be addressed.

Archives of Physical Medicine and Rehabilitation, 2012

Disclosure: Magstim 200. Objective: Demonstrate safety and efficacy of repetitive transcranial ma... more Disclosure: Magstim 200. Objective: Demonstrate safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) for severe traumatic brain injury (TBI). Design: Baseline-Control Pilot. Setting: Medical research unit. Participants: Two men in vegetative state for 287 and 188 days. Poor recovery likelihood indicated by low odds (27% ; 45%) for regaining consciousness and unresponsiveness to somatosensory evoked potentials (SSEP). rTMS subjects are compared with controls (n ϭ 22) admitted to rehabilitation an average of 54 days after TBI. Intervention: 30 rTMS sessions without neurostimulants. Main Outcomes: For both groups, neurobehavioral functioning measured for six weeks with the Disorders of Consciousness Scale (DOCS). For rTMS, functional imaging, diffusion tensor imaging (DTI), functional connectivity, brainstem auditory evoked potentials, SSEP and safety data collected at least weekly. Results: No adverse events. rTMS # 1 progressed from non-responsive to inconsistent command following and answering yes/no questions (DOCS gain ϭ 15.2). rTMS # 2 progressed from non-responsive to consistent communication in sentences (DOCS gainϭ 9.7). rTMS subjects achieved greater DOCS gains than average control gains (9.2). Region of interest, functional connectivity and DTI findings indicate that rTMS neurobeahvioral gains related to increasing number and strength of significantly (p ϭ 0.001) correlated regions and between the Brainstem, Thalamus, Wernicke's and Heschl's. Patterns corresponding with more function (#2), relative to less (#1), include increasing strength of some correlations simultaneous with decreasing strength of others s (e. g. midbrain to thalamus) and bilateral rather than only ipsilateral changes. Conclusions: DOCS gains during rTMS exceed controls' gains and correspond with changes in brainstem-thalamo-cortical connections.

The computing …, Jan 3, 1989

Google, Inc. (search). ...

The Journal of Immunology

We have studied the effects of immune complexes on the expression of macrophage surface proteins ... more We have studied the effects of immune complexes on the expression of macrophage surface proteins in vitro. Increased expression of the H-2 molecules I-A, I-E, and K on the macrophage membrane was induced by in vitro culture with crude lymphokine or interferon-gamma. Expression of all three of the molecules was additionally increased by stimulating the cultures with heat-killed Listeria monocytogenes. Addition of soluble immune complexes to the cultures did not have any effect on macrophage expression of these proteins. However, significant inhibition of lymphokine or interferon-gamma induction of I-A, I-E, and H-2K was observed when macrophages were cultured on plates to which immune complexes had been bound. This inhibition was dose dependent, required an immunoglobulin (Ig) molecule with an intact Fc portion, did not require the presence of T cells, and occurred in the presence of indomethacin. Complexes containing IgG1, IgG2a, IgG2b, and IgE, but not IgM or IgA, antibodies mediat...

IEEE Transactions on Neural Systems and Rehabilitation Engineering

We aim to build a system incorporating electroencephalography (EEG) and augmented reality (AR) th... more We aim to build a system incorporating electroencephalography (EEG) and augmented reality (AR) that is capable of identifying the presence of visual spatial neglect (SN) and mapping the estimated neglected visual field. An EEG-based brain-computer interface (BCI) was used to identify those spatiospectral features that best detect participants with SN among stroke survivors using their EEG responses to ipsilesional and contralesional visual stimuli. Frontal-central delta and alpha, frontalparietal theta, Fp1 beta, and left frontal gamma were found to be important features for neglect detection. Additionally, temporal analysis of the responses shows that the proposed model is accurate in detecting potentially neglected targets. These targets were predicted using common spatial patterns as the feature extraction algorithm and regularized discriminant analysis combined with kernel density estimation for classification. With our preliminary results, our system shows promise for reliably detecting

2021 43rd Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), 2021

Spatial neglect (SN) is a neurological disorder that causes inattention to visual stimuli in the ... more Spatial neglect (SN) is a neurological disorder that causes inattention to visual stimuli in the contralesional visual field, stemming from unilateral brain injury such as stroke. The current gold standard method of SN assessment, the conventional Behavioral Inattention Test (BIT-C), is highly variable and inconsistent in its results. In our previous work, we built an augmented reality (AR)-based BCI to overcome the limitations of the BIT-C and classified between neglected and nonneglected targets with high accuracy. Our previous approach included personalization of the neglect detection classifier but the process required rigorous retraining from scratch and timeconsuming feature selection for each participant. Future steps of our work will require rapid personalization of the neglect classifier; therefore, in this paper, we investigate fine-tuning of a neural network model to hasten the personalization process. Clinical relevance-The proposed approach will utilize EEG data from multiple individuals, and enable rapid adaptation of the neglect classifier to each specific participant's EEG that could be collected over multiple days. Further research will investigate important EEG channels and it will provide a robust modality for online EEG-guided neglect detection and rehabilitation.

2020 42nd Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), 2020

Spatial neglect (SN) is a neurological syndrome in stroke patients, commonly due to unilateral br... more Spatial neglect (SN) is a neurological syndrome in stroke patients, commonly due to unilateral brain injury. It results in inattention to stimuli in the contralesional visual field. The current gold standard for SN assessment is the behavioral inattention test (BIT). BIT includes a series of penand-paper tests. These tests can be unreliable due to high variablility in subtest performances; they are limited in their ability to measure the extent of neglect, and they do not assess the patients in a realistic and dynamic environment. In this paper, we present an electroencephalography (EEG)-based brain-computer interface (BCI) that utilizes the Starry Night Test to overcome the limitations of the traditional SN assessment tests. Our overall goal with the implementation of this EEG-based Starry Night neglect detection system is to provide a more detailed assessment of SN. Specifically, to detect the presence of SN and its severity. To achieve this goal, as an initial step, we utilize a convolutional neural network (CNN) based model to analyze EEG data and accordingly propose a neglect detection method to distinguish between stroke patients without neglect and stroke patients with neglect.Clinical relevance—The proposed EEG-based BCI can be used to detect neglect in stroke patients with high accuracy, specificity and sensitivity. Further research will additionally allow for an estimation of a patient’s field of view (FOV) for more detailed assessment of neglect.

Archives of Physical Medicine and Rehabilitation, 2021

Toxicon, 2021

For José Nuno Oliveira, on his 60th birthday A classical result in algebraic specification states... more For José Nuno Oliveira, on his 60th birthday A classical result in algebraic specification states that a total function defined on an initial algebra is a homomorphism if and only if the kernel of that function is a congruence. We expand on the discussion of that result from an earlier paper: extending it from total to partial functions, simplifying the proofs using relational calculus, and generalising the setting to regular categories.

Infection and Immunity, 1985

We have investigated possible mechanisms underlying immune complex suppression of resistance to L... more We have investigated possible mechanisms underlying immune complex suppression of resistance to Listeria monocytogenes. Inhibition of resistance was found when immune complexes were formed in vivo in immune mice or in nonimmune mice adoptively transferred with specific antibody. Suppression was also found when nonimmune mice were injected with immune complexes preformed in vitro. We investigated the role of complement by decomplementing mice with cobra venom factor purified by high-pressure liquid chromatography. Complete depletion of serum C3 did not eliminate immune complex suppression of resistance to L. monocytogenes, suggesting that complement activation is not required for immune complex suppression. Infection-induced changes in the surface phenotype and functional properties of macrophages from normal and immune complex-suppressed mice were also investigated. Macrophage expression of both H-2K and Ia molecules increased during the response of normal mice to L. monocytogenes. ...