Congrats Team! Our research paper entitled, "Working memory revived in older adults by synchronizing rhythmic brain circuits," made the 2019 Altmetric Top 100, as one of the most-discussed and shared pieces of research published in the past year (ranked in the top 0.007% of all discussed research this year). https://www.altmetric.com/top100/2019/

Congratulations, Breanna Bullard for presenting her exciting new brain stimulation findings at the Boston University Underrepresented Graduate Student Organization (UGSO) Academic Research Symposium!

Postdoc in electrophysiology and noninvasive brain stimulation

Our laboratory is seeking a postdoctoral researcher interested in gaining experience in the cognitive neuroscience of learning and memory in healthy younger and older adults using behavior, electrophysiological measurements of rhythmic brain activity, and noninvasive neuromodulation. This position is funded by the National Institute of Mental Health and the National Institute of Aging. Applicants must have a Ph.D. in neuroscience, psychology or a related field, and should possess a strong background in programming (preferably Python or Matlab), electrophysiology, and mathematics. For more information, please contact Rob Reinhart at rmgr@bu.edu.

Working memory revived in older adults by synchronizing rhythmic brain circuits

Nature Neuroscience

Reinhart RMG & Nguyen JA

Understanding normal brain aging and developing methods to maintain or improve cognition in older adults are major goals of fundamental and translational neuroscience. Here, we show a core feature of cognitive decline - working memory deficits - emerges from disconnected local and long-range circuits instantiated by theta-gamma phase-amplitude codes in temporal cortex and theta phase synchronization across frontotemporal cortex. We developed a noninvasive stimulation procedure for modulating long-range theta interactions in adults aged 60-76 years. After 25 minutes of stimulation, frequency tuned to individual brain network dynamics, we observed a preferential increase in neural synchronization patterns and the return of sender-receiver relationships of information flow within and between frontotemporal regions. The end result was rapid improvement in working memory performance that outlasted a 50-minute post-stimulation period. The results provide insight into the physiological foundations of age-related cognitive impairment and contribute groundwork for future non-pharmacological interventions targeting aspects of cognitive decline.

Congratulations, Charlotte Xiyou Wang on being awarded Undergraduate Research Opportunity Program (UROP) funding for the summer!

Localization and elimination of attentional dysfunction in schizophrenia during visual search

Schizophrenia Bulletin

Reinhart RMG, Park S, Woodman GF

Theories of the locus of visual selective attention dysfunction in schizophrenia propose that the deficits arise from either an inability to maintain working memory representations that guide attention, or difficulty focusing lower-level visual attention mechanisms. However, these theoretical accounts neglect the role of long-term memory representations in controlling attention. Here we show that the control of visual attention is impaired in people with schizophrenia, and that this impairment is driven by an inability to shift top-down attentional control from working memory to long-term memory across practice. Next, we provide converging evidence for the source of attentional impairments in long-term memory by showing that noninvasive electrical stimulation of medial frontal cortex normalizes long-term memory related neural signatures and patients’ behavior. Our findings suggest that long-term memory structures may be a source of impaired attentional selection in schizophrenia when visual attention is taxed during the processing of multi-object arrays.

Disruption and rescue of interareal theta phase coupling and adaptive behavior.

Proceedings of the National Academy of Sciences, USA.

Reinhart RMG

Rescuing executive functions in people with neurological and neuropsychiatric disorders has been a major goal of psychology and neuroscience for decades. Innovative computer-training regimes for executive functions have made tremendous inroads, yet the positive effects of training have not always translated into improved cognitive functioning and often take many days to emerge. In the present study, we asked whether it was possible to immediately change components of executive function by directly manipulating neural activity using a stimulation technology called high-definition transcranial alternating current stimulation (HDtACS). Twenty minutes of inphase stimulation over medial frontal cortex (MFC) and right lateral prefrontal cortex (lPFC) synchronized theta (∼6 Hz) rhythms between these regions in a frequency and spatially specific manner and rapidly improved adaptive behavior with effects lasting longer than 40 min. In contrast, antiphase stimulation in the same individuals desynchronized MFC-lPFC theta phase coupling and impaired adaptive behavior. Surprisingly, the exogenously driven impairments in performance could be instantly rescued by reversing the phase angle of alternating current. The results suggest executive functions can be rapidly up- or down-regulated by modulating theta phase coupling of distant frontal cortical areas and can contribute to the development of tools for potentially normalizing executive dysfunction in patient populations.

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Using transcranial direct-current stimulation (tDCS) to understand cognitive processing

Attention, Perception, & Psychophysics

Reinhart RMG, Fukuda K, Cosman JD, Woodman GF

Noninvasive brain stimulation methods are becoming increasingly common tools in the kit of the cognitive scientist. In particular, transcranial direct-current stimulation (tDCS) is showing great promise as a tool to causally manipulate the brain and understand how information is processed. The popularity of this method of brain stimulation is based on the fact that it is safe, inexpensive, its effects are long lasting, and you can increase the likelihood that neurons will fire near one electrode and decrease the likelihood that neurons will fire near another. However, this method of manipulating the brain to draw causal inferences is not without complication. Because tDCS methods continue to be refined and are not yet standardized, there are reports in the literature that show some striking inconsistencies. Primary among the complications of the technique is that the tDCS method uses two or more electrodes to pass current and all of these electrodes will have effects on the tissue underneath them. In this tutorial, we will share what we have learned about using tDCS to manipulate how the brain perceives, attends, remembers, and responds to information from our environment. Our goal is to provide a starting point for new users of tDCS and spur discussion of the standardization of methods to enhance replicability.

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Attention's accelerator

Psychological Science

Reinhart RMG, McClenahan L, Woodman GF

How do people get attention to operate at peak efficiency in high-pressure situations? We tested the hypothesis that the general mechanism that allows this is the maintenance of multiple target representations in working and long-term memory. We recorded subjects’ event-related potentials (ERPs) indexing the working memory and long-term memory representations used to control attention while performing visual search. We found that subjects used both types of memories to control attention when they performed the visual search task with a large reward at stake, or when they were cued to respond as fast as possible. However, under normal circumstances, one type of target memory was sufficient for slower task performance. The use of multiple types of memory representations appears to provide converging top-down control of attention, allowing people to step on the attentional accelerator in a variety of high-pressure situations.

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Role of n-methyl d-aspartate receptors in action-based predictive coding deficits in schizophrenia

Biological Psychiatry

Kort NS, Ford JM, Roach BJ, Gunduz-Bruce H, Krystal JH, Jaeger J, Reinhart RMG, Mathalon DH

Background. Recent theoretical models of schizophrenia posit that dysfunction of the neural mechanisms subserving predictive coding contributes to symptoms and cognitive deficits, and this dysfunction is further posited to result from N-Methyl D-aspartate glutamate receptor (NMDAR) hypofunction. Previously, by examining auditory cortical responses to self-generated speech sounds, we demonstrated that predictive coding during vocalization is disrupted in schizophrenia. In order to test the hypothesized contribution of NMDAR hypofunction to this disruption, we examined the effects of the NMDAR antagonist, ketamine, on predictive coding during vocalization in healthy volunteers and compared them to the effects of schizophrenia. Methods. In two separate studies, the N1 component of the event-related potential (ERP) elicited by speech sounds during vocalization (Talk) and passive playback (Listen) were compared to assess the degree of N1 suppression during vocalization, a putative measure of auditory predictive coding. In the cross-over study, 31 healthy volunteers completed two randomly ordered test days, a saline day and a ketamine day. ERPs during the Talk/Listen task were obtained pre-infusion and during infusion on both days, and N1 amplitudes were compared across days. In the case-control study, N1 amplitudes from 34 schizophrenia patients and 33 healthy controls were compared. Results. N1 suppression to self-produced vocalizations was significantly and similarly diminished by ketamine (Cohen’s d=1.14) and schizophrenia (Cohen’s d=.85). Conclusions. Disruption of NMDARs causes dysfunction in predictive coding during vocalization in a manner similar to the dysfunction observed in schizophrenia patients, consistent with the theorized contribution of NMDAR hypofunction to predictive coding deficits in schizophrenia.

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