Assistant Professor, Department of Human Physiology
Ph.D. University of California, San Diego
B.A Tufts University
Ian Greenhouse’s research examines how humans initiate and cancel movement. His lab combines behavioral testing with electrophysiology, neuroimaging, and brain stimulation in healthy and clinical populations. His current research explores the relationship between the inhibitory neurochemical gamma-aminobutyric acid (GABA) and motor performance.
Dr. Greenhouse earned his BA in Psychology at Tufts University and his Ph.D. at the University of California, San Diego. He completed postdoctoral training at the University of California, Berkeley. He joined the Department of Human Physiology at the University of Oregon in the Fall of 2017.
The Neural Specificity of Movement Preparation During Actual and Imagined Movements.
Cereb Cortex. 2019 Feb 01;29(2):689-700
Authors: Lebon F, Ruffino C, Greenhouse I, Labruna L, Ivry RB, Papaxanthis C
Current theories consider motor imagery, the mental representation of action, to have considerable functional overlap with the processes involved in actual movement preparation and execution. To test the neural specificity of motor imagery, we conducted a series of 3 experiments using transcranial magnetic stimulation (TMS). We compared changes in corticospinal excitability as people prepared and implemented actual or imagined movements, using a delayed response task in which a cue indicated the forthcoming response. TMS pulses, used to elicit motor-evoked responses in the first dorsal interosseous muscle of the right hand, were applied before and after an imperative signal, allowing us to probe the state of excitability during movement preparation and implementation. Similar to previous work, excitability increased in the agonist muscle during the implementation of an actual or imagined movement. Interestingly, preparing an imagined movement engaged similar inhibitory processes as that observed during actual movement, although the degree of inhibition was less selective in the imagery conditions. These changes in corticospinal excitability were specific to actual/imagined movement preparation, as no modulation was observed when preparing and generating images of cued visual objects. Taken together, inhibition is a signature of how actions are prepared, whether they are imagined or actually executed.
PMID: 29309536 [PubMed - in process]
Big GABA: Edited MR spectroscopy at 24 research sites.
Neuroimage. 2017 10 01;159:32-45
Authors: Mikkelsen M, Barker PB, Bhattacharyya PK, Brix MK, Buur PF, Cecil KM, Chan KL, Chen DY, Craven AR, Cuypers K, Dacko M, Duncan NW, Dydak U, Edmondson DA, Ende G, Ersland L, Gao F, Greenhouse I, Harris AD, He N, Heba S, Hoggard N, Hsu TW, Jansen JFA, Kangarlu A, Lange T, Lebel RM, Li Y, Lin CE, Liou JK, Lirng JF, Liu F, Ma R, Maes C, Moreno-Ortega M, Murray SO, Noah S, Noeske R, Noseworthy MD, Oeltzschner G, Prisciandaro JJ, Puts NAJ, Roberts TPL, Sack M, Sailasuta N, Saleh MG, Schallmo MP, Simard N, Swinnen SP, Tegenthoff M, Truong P, Wang G, Wilkinson ID, Wittsack HJ, Xu H, Yan F, Zhang C, Zipunnikov V, Zöllner HJ, Edden RAE
Magnetic resonance spectroscopy (MRS) is the only biomedical imaging method that can noninvasively detect endogenous signals from the neurotransmitter γ-aminobutyric acid (GABA) in the human brain. Its increasing popularity has been aided by improvements in scanner hardware and acquisition methodology, as well as by broader access to pulse sequences that can selectively detect GABA, in particular J-difference spectral editing sequences. Nevertheless, implementations of GABA-edited MRS remain diverse across research sites, making comparisons between studies challenging. This large-scale multi-vendor, multi-site study seeks to better understand the factors that impact measurement outcomes of GABA-edited MRS. An international consortium of 24 research sites was formed. Data from 272 healthy adults were acquired on scanners from the three major MRI vendors and analyzed using the Gannet processing pipeline. MRS data were acquired in the medial parietal lobe with standard GABA+ and macromolecule- (MM-) suppressed GABA editing. The coefficient of variation across the entire cohort was 12% for GABA+ measurements and 28% for MM-suppressed GABA measurements. A multilevel analysis revealed that most of the variance (72%) in the GABA+ data was accounted for by differences between participants within-site, while site-level differences accounted for comparatively more variance (20%) than vendor-level differences (8%). For MM-suppressed GABA data, the variance was distributed equally between site- (50%) and participant-level (50%) differences. The findings show that GABA+ measurements exhibit strong agreement when implemented with a standard protocol. There is, however, increased variability for MM-suppressed GABA measurements that is attributed in part to differences in site-to-site data acquisition. This study's protocol establishes a framework for future methodological standardization of GABA-edited MRS, while the results provide valuable benchmarks for the MRS community.
PMID: 28716717 [PubMed - indexed for MEDLINE]
Physiological Markers of Motor Inhibition during Human Behavior.
Trends Neurosci. 2017 04;40(4):219-236
Authors: Duque J, Greenhouse I, Labruna L, Ivry RB
Transcranial magnetic stimulation (TMS) studies in humans have shown that many behaviors engage processes that suppress excitability within the corticospinal tract. Inhibition of the motor output pathway has been extensively studied in the context of action stopping, where a planned movement needs to be abruptly aborted. Recent TMS work has also revealed markers of motor inhibition during the preparation of movement. Here, we review the evidence for motor inhibition during action stopping and action preparation, focusing on studies that have used TMS to monitor changes in the excitability of the corticospinal pathway. We discuss how these physiological results have motivated theoretical models of how the brain selects actions, regulates movement initiation and execution, and switches from one state to another.
PMID: 28341235 [PubMed - indexed for MEDLINE]
Individual Differences in Resting Corticospinal Excitability Are Correlated with Reaction Time and GABA Content in Motor Cortex.
J Neurosci. 2017 03 08;37(10):2686-2696
Authors: Greenhouse I, King M, Noah S, Maddock RJ, Ivry RB
Individuals differ in the intrinsic excitability of their corticospinal pathways and, perhaps more generally, their entire nervous system. At present, we have little understanding of the mechanisms underlying these differences and how variation in intrinsic excitability relates to behavior. Here, we examined the relationship between individual differences in intrinsic corticospinal excitability, local cortical GABA levels, and reaction time (RT) in a group of 20 healthy human adults. We measured corticospinal excitability at rest with transcranial magnetic stimulation, local concentrations of basal GABA with magnetic resonance spectroscopy, and RT with a behavioral task. All measurements were repeated in two separate sessions, and tests of reliability confirmed the presence of stable individual differences. There was a negative correlation between corticospinal excitability and RT, such that larger motor-evoked potentials (MEPs) measured at rest were associated with faster RTs. Interestingly, larger MEPs were associated with higher levels of GABA in M1, but not in three other cortical regions. Together, these results suggest that individuals with more excitable corticospinal pathways are faster to initiate planned responses and have higher levels of GABA within M1, possibly to compensate for a more excitable motor system.SIGNIFICANCE STATEMENT This study brings together physiological, behavioral, and neurochemical evidence to examine variability in the excitability of the human motor system. Previous work has focused on state-based factors (e.g., preparedness, uncertainty), with little attention given to the influence of inherent stable characteristics. Here, we examined how the excitability of the motor system relates to reaction time and the regional content of the inhibitory neurotransmitter GABA. Importantly, motor pathway excitability and GABA concentrations were measured at rest, outside a task context, providing assays of intrinsic properties of the individuals. Individuals with more excitable motor pathways had faster reaction times and, paradoxically, higher concentrations of GABA. We propose that greater GABA capacity in the motor cortex counteracts an intrinsically more excitable motor system.
PMID: 28179557 [PubMed - indexed for MEDLINE]
Individual differences in GABA content are reliable but are not uniform across the human cortex.
Neuroimage. 2016 Oct 01;139:1-7
Authors: Greenhouse I, Noah S, Maddock RJ, Ivry RB
1H magnetic resonance spectroscopy (MRS) provides a powerful tool to measure gamma-aminobutyric acid (GABA), the principle inhibitory neurotransmitter in the human brain. We asked whether individual differences in MRS estimates of GABA are uniform across the cortex or vary between regions. In two sessions, resting GABA concentrations in the lateral prefrontal, sensorimotor, dorsal premotor, and occipital cortices were measured in twenty-eight healthy individuals. GABA estimates within each region were stable across weeks, with low coefficients of variation. Despite this stability, the GABA estimates were not correlated between regions. In contrast, the percentage of brain tissue per volume, a control measure, was correlated between the three anterior regions. These results provide an interesting dissociation between an anatomical measure of individual differences and a neurochemical measure. The different patterns of anatomy and GABA concentrations have implications for understanding regional variation in the molecular topography of the brain in health and disease.
PMID: 27288552 [PubMed - indexed for MEDLINE]
Nonspecific Inhibition of the Motor System during Response Preparation.
J Neurosci. 2015 Jul 29;35(30):10675-84
Authors: Greenhouse I, Sias A, Labruna L, Ivry RB
UNLABELLED: Motor system excitability is transiently inhibited during the preparation of responses. Previous studies have attributed this inhibition to the operation of two mechanisms, one hypothesized to help resolve competition between alternative response options, and the other to prevent premature response initiation. By this view, inhibition should be restricted to task-relevant muscles. Although this prediction is supported in one previous study (Duque et al., 2010), studies of stopping ongoing actions suggest that some forms of motor inhibition may be widespread (Badry et al., 2009). This motivated us to conduct a series of transcranial magnetic stimulation (TMS) experiments to examine in detail the specificity of preparatory inhibition in humans. Motor-evoked potentials were inhibited in task-irrelevant muscles during response preparation, even when the muscles were contralateral and not homologous to the responding effector. Inhibition was also observed in both choice and simple response task conditions, with and without a preparatory interval. Control experiments ruled out that this inhibition is due to expectancy of TMS or a possible need to cancel the prepared response. These findings suggest that motor inhibition during response preparation broadly influences the motor system and likely reflects a process that occurs whenever a response is selected. We propose a reinterpretation of the functional significance of preparatory inhibition, one by which inhibition reduces noise to enhance signal processing and modulates the gain of a selected response.
SIGNIFICANCE STATEMENT: Motor preparation entails the recruitment of excitatory and inhibitory neural mechanisms. The current experiments address the specificity of inhibitory mechanisms, asking whether preparatory inhibition affects task-irrelevant muscles. Participants prepared a finger movement to be executed at the end of a short delay period. Transcranial magnetic stimulation over primary motor cortex provided an assay of corticospinal excitability. Consistent with earlier work, the agonist muscle for the forthcoming response was inhibited during the preparatory period. Moreover, this inhibition was evident in task-irrelevant muscles, although the magnitude of inhibition depended on whether the response was fixed or involved a choice. These results implicate a broadly tuned inhibitory mechanism that facilitates response preparation, perhaps by lowering background activity before response initiation.
PMID: 26224853 [PubMed - indexed for MEDLINE]
Influence of Delay Period Duration on Inhibitory Processes for Response Preparation.
Cereb Cortex. 2016 06;26(6):2461-70
Authors: Lebon F, Greenhouse I, Labruna L, Vanderschelden B, Papaxanthis C, Ivry RB
In this study, we examined the dynamics of inhibitory preparatory processes, using a delayed response task in which a cue signaled a left or right index finger (Experiment 1) or hand (Experiment 2) movement in advance of an imperative signal. In Experiment 1, we varied the duration of the delay period (200, 500, and 900 ms). When transcranial magnetic stimulation (TMS) was applied 100 ms before the imperative, motor evoked potentials (MEPs) elicited in the first dorsal interosseous were strongly inhibited. For delays of 500 ms or longer, this inhibition was greater when the targeted muscle was selected compared with when it was not selected. In contrast, the magnitude of inhibition just after the cue was inversely related to the duration of the delay period, and the difference between the selected and nonselected conditions was attenuated. In Experiment 2, TMS and peripheral nerve stimulation procedures were used during a 300-ms delay period. MEPs in the flexor carpi radialis for both selected and nonselected conditions were inhibited, but without any change in the H-reflex. Taken together, these results reveal the dual influence of temporal constraints associated with anticipation and urgency on inhibitory processes recruited during response preparation.
PMID: 25882038 [PubMed - indexed for MEDLINE]
Inhibition during response preparation is sensitive to response complexity.
J Neurophysiol. 2015 Apr 01;113(7):2792-800
Authors: Greenhouse I, Saks D, Hoang T, Ivry RB
Motor system excitability is transiently suppressed during the preparation of movement. This preparatory inhibition is hypothesized to facilitate response selection and initiation. Given that demands on selection and initiation processes increase with movement complexity, we hypothesized that complexity would influence preparatory inhibition. To test this hypothesis, we probed corticospinal excitability during a delayed-response task in which participants were cued to prepare right- or left-hand movements of varying complexity. Single-pulse transcranial magnetic stimulation was applied over right primary motor cortex to elicit motor evoked potentials (MEPs) from the first dorsal interosseous (FDI) of the left hand. MEP suppression was greater during the preparation of responses involving coordination of the FDI and adductor digiti minimi relative to easier responses involving only the FDI, independent of which hand was cued to respond. In contrast, this increased inhibition was absent when the complex responses required sequential movements of the two muscles. Moreover, complexity did not influence the level of inhibition when the response hand was fixed for the trial block, regardless of whether the complex responses were performed simultaneously or sequentially. These results suggest that preparatory inhibition contributes to response selection, possibly by suppressing extraneous movements when responses involve the simultaneous coordination of multiple effectors.
PMID: 25717168 [PubMed - indexed for MEDLINE]