Boston University Cognitive & Clinical Neuroscience Laboratory

Research in the laboratory seeks to understand (i) the nature of visual perception and cognition (e.g., attention, working memory, executive control, learning) in the healthy adult brain, (ii) how these processes break down in normal aging and neuropsychiatric illnesses, such as schizophrenia, and (iii) how we can leverage insights from basic and clinical science to develop novel interventions for optimizing cognition in healthy people and restoring abilities in aging and patient populations.
In our laboratory, we examine cognitive mechanisms from a physiologically inspired perspective centered on large-scale brain networks and how they interact through synchronized electrophysiological rhythms. We focus on the phase, frequency, and power of local electroencephalographic (EEG) rhythms, as well as a variety of neural coding schemes, such as cross-frequency coupling and phase synchronization, hypothesized to index flexible cortical circuits that integrate information across multiple temporal and spatial scales during cognition. We combine measures of EEG rhythms and their synchronization with source reconstruction methods (e.g., beamforming) to improve reasoning about the spatial location of these neural signals and networks.
Although the correlational cognitive neuroscience methods that we use in our research provide fast progress and rapid hypothesis testing, we believe that obtaining causal control over neural activity is one of the best ways to understand how information is processed in the human brain. To this end, our research utilizes neuromodulation techniques, such as transcranial direct-current stimulation (tDCS) and transcranial alternating-current stimulation (tACS). Our expertise with noninvasive neuromodulation allows us to establish causal relationships between brain activity and behavior, and build customized stimulation protocols for boosting mental functions in healthy and patient populations.
Finally, we believe a strong scientific approach involves the use of converging evidence from multiple methods, levels of analysis, and subject groups. Thus, in addition to expertise with behavioral (e.g., eye tracking, psychophysics), electrophysiological, and noninvasive neuromodulation techniques, we also employ computational modeling and neuroimaging methods, and are expanding our patient populations to include Alzheimer’s disease, obsessive-compulsive disorder, generalized anxiety disorder, and depression.

Current areas of investigation

Reactive Executive Control

How does the human brain control information processing and actions, allowing us to override habits and routines to make better decisions and learn? Our ongoing research examines the dynamic neural processing of reactive executive function using control-related electrophysiology (e.g., ERN, FRN, Pe, N2, theta coherence) and source reconstruction methods (e.g., surface Laplace, beamforming, minimum norm), behavioral adjustments (e.g., post-error slowing, adjustment efficiency), and noninvasive neuromodulation (e.g., tDCS, HD-tACS). The results from this line of work have clarified how the neural mechanisms of medial frontal cortex monitor ongoing actions and their outcomes, recruit lateral prefrontal regions for implementing behavioral adjustments, and generate training signals to drive learning.
Nguyen JA, Deng Y, Reinhart RMG (2018). Brain-state determines learning improvements after transcranial alternating-current stimulation to frontal cortex. Brain Stimulation. 11(4):723-726
Reinhart RMG (2017). Disruption and rescue of interareal theta phase coupling and adaptive behavior. Proceedings of the National Academy of Sciences, USA. 114(43):11542-11547.
Reinhart RMG, Zhu J, Park S, Woodman GF (2015). Synchronizing theta oscillations with direct-current stimulation strengthens adaptive control in the human brain. Proceedings of the National Academy of Sciences, USA. 112(30):9448-9453.
Reinhart RMG & Woodman GF (2014). Causal control of medial-frontal cortex governs electrophysiological and behavioral indices of performance monitoring and learning. Journal of Neuroscience. 34(12):4214-4227.
Reinhart RMG, Carlisle NB, Kang S, Woodman GF (2012). Event-related potentials elicited by errors during the stop-signal task. II: Human effector specific error responses. Journal of Neurophysiology. 107:2794-807.

Proactive Executive Control

How do the visual working memory and long-term memory systems proactively drive perceptual attention during the analysis of complex visual scenes? Our current research examining proactive executive control is focused on the visual working memory and long-term memory systems that guide perceptual attention during the analysis of complex visual scenes. In this line of work, we have proposed the new hypothesis that superior attentional performance is due to the over-representation of task-relevant information being stored in working and long-term memory. Using novel behavioral paradigms (e.g., memory-guided visual search), and methods of EEG (e.g., alpha coherence and power, cross-frequency coupling, time lag cross correlation) and event-related potentials (ERPs; e.g., CDA, Anterior P1, N2pc, P1, N1), we have shown how the brain stores redundant target information across memory systems and dynamically uses these additional resources to improve performance in a variety of situations calling for greater attentional control and behavioral efficiency, including when obtaining a large reward is possible, when subjects are under great pressure, or when attention is being trained using mental imagery. In addition, this work has provided a causal demonstration of the redundant target template hypothesis. We have shown that it is possible to use noninvasive electrical brain stimulation to enhance visual attention by accelerating the time at which long-term memory representations come online to supplement the working memory representations controlling attention, as subjects become proficient at performing a task.
Woodman GF, Wang S, Sutterer D, Reinhart RMG, Fukuda K (2021). Alpha suppression indexes a spotlight of visual-spatial attention that can shine on both perceptual and memory representations.
Psychonomic Bulletin & Review.
Grover S, Reinhart RMG (2019). Combining transcranial stimulation and electrophysiology to understand the memory representations that guide attention. In: Spatial Learning and Attention Guidance. Pollmann S. (Ed). Neuromethods. Humana Press. pp. 1-29.
Reinhart RMG, McClenahan L, Woodman GF (2016). Attention’s accelerator. Psychological Science. 27(6):790-798.
Reinhart RMG, McClenahan L, Woodman GF (2015). Visualizing trumps vision in training attention. Psychological Science. 26(7):1114-1122.
Reinhart RMG & Woodman GF (2015). Enhanced long-term memories after stimulation tune visual attention in one trial. Proceedings of the National Academy of Sciences, USA. 112(2):625-630.
Reinhart RMG & Woodman GF (2014). High stakes trigger the use of multiple memories to enhance cognitive control of attention. Cerebral Cortex. 24(8):2022-2035.
Reinhart RMG & Woodman GF (2014). Oscillatory coupling reveals the dynamic reorganization of large-scale neural networks as cognitive demands change. Journal of Cognitive Neuroscience. 26(1):175-188.
Reinhart RMG, Carlisle NB, Woodman GF (2014). Visual working memory gives up attentional control early in learning ruling out inter-hemispheric cancellation. Psychophysiology. 51(8):800-804.
Woodman GF, Carlisle NB, Reinhart RMG (2013). Where do we store the memory representations that guide attention? Journal of Vision. 13(3):1-17.
Reinhart RMG, Heitz RP, Purcell BA, Weigand PK, Schall JD, Woodman GF (2012). Homologous mechanisms of visuospatial working memory maintenance in macaque and human: Properties and sources. Journal of Neuroscience. 32(22):7711-7722.

Executive Dysfunction in Schizophrenia

What are the neurobiological bases for the symptoms and disturbances in neuropsychiatric disorders, such as schizophrenia? Schizophrenia is the most debilitating disorder known, surpassing metastatic cancer, multiple sclerosis, and untreated AIDS. While schizophrenia is most well known for its remarkable psychotic symptoms, such as hallucinations and delusions, it is actually the cognitive deficits associated with the illness that are the primary drivers of functional disability. Our contributions to schizophrenia research have focused on the neural mechanisms of cognitive dysfunction using EEG (e.g., gamma power, theta coherence), ERPs (e.g., CDA, anterior P1, ERN, C1, N1b) and noninvasive neuromodulation (e.g., tDCS). We have shown how abnormal electrophysiological indices of frontal cortical mechanisms (e.g., theta coherence, ERN) underlie adaptive control, learning, and long-term memory impairments in schizophrenia, and how these neural signatures can be rectified using noninvasive brain stimulation, removing differences between people with schizophrenia and healthy controls in terms of error-related electrophysiology, post-error behavioral adjustments, stimulus-response learning, and attentional performance. In addition, we have shown impaired plasticity in the visual cortex of people with schizophrenia using a long-term potentiation paradigm and set of early visually evoked potentials (C1, N1b) and EEG steady-state responses.
Roach BJ, Ford JM, Ferri JM, Gunduz-Bruce H, Krystal JH, Jaeger J, Reinhart RMG, O’Leary D, Mathalon DH (in review). Gamma oscillations and excitation/inhibition imbalance: Parallel effects of N-Methyl D-Aspartate receptor antagonism and psychosis.
Raymond N, Reinhart RMG, Keshavan M, Lizano P (2022). An integrated neuroimaging approach to inform transcranial electrical stimulation targeting in visual hallucinations. Harvard Review of Psychiatry.
Grover S, Keshavan MS, Lizano PL, Reinhart RMG (2021). Proximate markers of cognitive dysfunction in schizophrenia. Schizophrenia Research.
Reinhart RMG, Park S, Woodman GF (2018). Localization and elimination of attentional dysfunction in schizophrenia during visual search. Schizophrenia Bulletin. 45(1):96-105.
Kort NS, Ford JM, Roach BJ, Gunduz-Bruce H, Krystal JH, Jaeger J, Reinhart RMG, Mathalon DH (2017). Role of N-methyl D-aspartate receptors in action-based predictive coding deficits in schizophrenia. Biological Psychiatry81(6):514-24.
Reinhart RMG, Zhu J, Park S, Woodman GF (2015). Synchronizing theta oscillations with direct-current stimulation strengthens adaptive control in the human brain. Proceedings of the National Academy of Sciences, USA. 112(30):9448-9453.
Reinhart RMG, Zhu J, Park S, Woodman GF (2015). Medial-frontal stimulation enhances learning in schizophrenia by restoring prediction-error signaling. Journal of Neuroscience. 35(35):12232-12240.
Cavus I, Reinhart RMG, Roach BJ, Gueorguieva R, Teyler TJ, Clapp WC, Ford JM, Krystal JH, Mathalon DH (2012). Impaired visual cortical plasticity in schizophrenia. Biological Psychiatry. 71(6):512-520.
Gunduz-Bruce H, Reinhart RMG, Roach BJ, Gueorguieva R, Oliver S, D’Souza DC, Ford JM, Krystal JH, Mathalon DH (2012). Glutamatergic modulation of auditory information processing in the human brain. Biological Psychiatry. 71:969-77.
Reinhart RMG, Mathalon DH, Roach BJ, Ford JM (2011). Relationships between pre-stimulus gamma power and subsequent P300 and reaction time break down in schizophrenia. International Journal of Psychophysiology. 79(1):16-24.

Noninvasive Electrical Brain Stimulation

Can we optimize patterns of human brain activity and performance in healthy people and people with neuropsychiatric disorders using safe, drug-free methods of noninvasive neuromodulation? Our contributions to science also include pioneering new noninvasive neuromodulation methods, models, and protocols for the development of neuroscience approaches toward understanding basic mechanisms, identifying biomarkers in brain disorders, and laying groundwork for safe, drug-free interventions for patients with cognitive impairments. With the goal of sharing with the broader scientific communities what we have learned about using noninvasive electrical stimulation to manipulate how the brain perceives, attends, remembers, and responds to information from our environment, as well as to spur discussion of the standardization of methods and enhance reproducibility, we have published a full-length tutorial on transcranial direct-current stimulation. We have also published a commentary on how direct-current stimulation can exert remarkable temporal precision in its influence of specific electrophysiological mechanisms that are as brief as 100 ms during a 1-5 second flow of information processing. Recently, we have developed HD-tACS protocols, uniquely tailored to individual brain oscillations and their synchronization, to probe behaviorally useful neural circuitry and improve key aspects of cognitive decline for older adults or address clinical symptoms of mental illnesses, such as obsessive-compulsive disorder.
Grover S, Reinhart RMG (in review). Rhythmic mechanisms of obsessive-compulsive disorder: New hypotheses and experimental therapeutic.
Grover S, Fayzullina R, Bullard BM, Levina V, Reinhart RMG (in review). Noninvasive rhythmic neuromodulation improves cognition in healthy, aging, and psychiatric populations: A systematic review and meta-analysis.
Reinhart RMG (accepted). Synchronizing neural rhythms: Personalized noninvasive network-based neuromodulation aids impaired cognition. Science.
Grover S, Wen W, Viswanathan V, Gill CT, Reinhart RMG (accepted). Long-lasting, dissociable improvements in working memory and long-term memory in older adults with repetitive neuromodulation. Nature Neuroscience.
Grover S, Nguyen JA, Viswanathan V, Reinhart RMG (2021). High-frequency neuromodulation improves obsessive-compulsive behavior. Nature Medicine. 27(2):232-238.
Grover S, Nguyen JA, Reinhart RMG (2021). Synchronizing brain rhythms to improve cognition. Annual Review of Medicine. 72:29-43.
Grover S, Reinhart RMG (2020). Modulating anterior midcingulate cortex using theta burst stimulation. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 5(11):1007-1008.
Deng Y, Reinhart RMG, Choi I, Shinn-Cunningham B (2019). Causal links between parietal alpha activity and spatial auditory attention. eLife. 8:e51184.
Reinhart RMG & Nguyen JA (2019). Working memory revived in older adults by synchronizing rhythmic brain circuits. Nature Neuroscience. 22(5):820-827.
Reinhart RMG, Cosman JD, Fukuda K, Woodman GF (2017). Using transcranial direct-current stimulation (tDCS) to understand cognitive processing. Attention, Perception & Psychophysics. 79(1):3-23
Reinhart RMG, Xiao W, McClenahan L, Woodman GF (2016). Electrical stimulation of visual cortex can immediately improve spatial vision. Current Biology26(14):1867-72.
Reinhart RMG & Woodman GF (2015). The surprising temporal specificity following direct-current stimulation. Trends in Neurosciences. 38(8):459-461.