Reporting Guidelines and Issues to Consider for Using Intracranial Brain Stimulation in Studies of Human Declarative Memory

Participants with stimulating and recording electrodes implanted within the brain for clinical evaluation and treatment provide a rare opportunity to unravel the neuronal correlates of human memory, as well as offer potential for modulation of behavior. Recent intracranial stimulation studies of memory have been inconsistent in methodologies employed and reported conclusions, which renders generalizations and construction of a framework impossible. In an effort to unify future study efforts and enable larger meta-analyses we propose in this mini-review a set of guidelines to consider when pursuing intracranial stimulation studies of human declarative memory and summarize details reported by previous relevant studies. We present technical and safety issues to consider when undertaking such studies and a checklist for researchers and clinicians to use for guidance when reporting results, including targeting, placement, and localization of electrodes, behavioral task design, stimulation and electrophysiological recording methods, details of participants, and statistical analyses. We hope that, as research in invasive stimulation of human declarative memory further progresses, these reporting guidelines will aid in setting standards for multicenter studies, in comparison of findings across studies, and in study replications

Repeating Spatial Activations in Human Entorhinal Cortex

SummaryThe ability to remember and navigate spatial environments is critical for everyday life. A primary mechanism by which the brain represents space is through hippocampal place cells, which indicate when an animal is at a particular location [1]. An important issue is understanding how the hippocampal place-cell network represents specific properties of the environment, such as signifying that a particular position is near a doorway or that another position is near the end of a corridor. The entorhinal cortex (EC), as the main input to the hippocampus, may play a key role in coding these properties because it contains neurons that activate at multiple related positions per environment [2–6]. We examined the diversity of spatial coding across the human medial temporal lobe by recording neuronal activity during virtual navigation of an environment containing four similar paths. Neurosurgical patients performed this task as we recorded from implanted microelectrodes, allowing us to compare the human neuronal representation of space with that of animals. EC neurons activated in a repeating manner across the environment, with individual cells spiking at the same relative location across multiple paths. This finding indicates that EC cells represent non-specific information about location relative to an environment’s geometry, unlike hippocampal place cells, which activate at particular random locations. Given that spatial navigation is considered to be a model of how the brain supports non-spatial episodic memory [7–10], these findings suggest that EC neuronal activity is used by the hippocampus to represent the properties of different memory episodes [2, 11]

Enhancing the Ecological Validity of fMRI Memory Research Using Virtual Reality

Functional magnetic resonance imaging (fMRI) is a powerful research tool to understand the neural underpinnings of human memory. However, as memory is known to be context-dependent, differences in contexts between naturalistic settings and the MRI scanner environment may potentially confound neuroimaging findings. Virtual reality (VR) provides a unique opportunity to mitigate this issue by allowing memories to be formed and/or retrieved within immersive, navigable, visuospatial contexts. This can enhance the ecological validity of task paradigms, while still ensuring that researchers maintain experimental control over critical aspects of the learning and testing experience. This mini-review surveys the growing body of fMRI studies that have incorporated VR to address critical questions about human memory. These studies have adopted a variety of approaches, including presenting research participants with VR experiences in the scanner, asking participants to retrieve information that they had previously acquired in a VR environment, or identifying neural correlates of behavioral metrics obtained through VR-based tasks performed outside the scanner. Although most such studies to date have focused on spatial or navigational memory, we also discuss the promise of VR in aiding other areas of memory research and facilitating research into clinical disorders

Specific responses of human hippocampal neurons are associated with better memory

A population of human hippocampal neurons has shown responses to individual concepts (e.g., Jennifer Aniston) that generalize to different instances of the concept. However, recordings from the rodent hippocampus suggest an important function of these neurons is their ability to discriminate overlapping representations, or pattern separate, a process that may facilitate discrimination of similar events for successful memory. In the current study, we explored whether human hippocampal neurons can also demonstrate the ability to discriminate between overlapping representations and whether this selectivity could be directly related to memory performance. We show that among medial temporal lobe (MTL) neurons, certain populations of neurons are selective for a previously studied (target) image in that they show a significant decrease in firing rate to very similar (lure) images. We found that a greater proportion of these neurons can be found in the hippocampus compared with other MTL regions, and that memory for individual items is correlated to the degree of selectivity of hippocampal neurons responsive to those items. Moreover, a greater proportion of hippocampal neurons showed selective firing for target images in good compared with poor performers, with overall memory performance correlated with hippocampal selectivity. In contrast, selectivity in other MTL regions was not associated with memory performance. These findings show that a substantial proportion of human hippocampal neurons encode specific memories that support the discrimination of overlapping representations. These results also provide previously unidentified evidence consistent with a unique role of the human hippocampus in orthogonalization of representations in declarative memory

Transcranial Focused Ultrasound Targeting the Amygdala May Increase Psychophysiological and Subjective Negative Emotional Reactivity in Healthy Older Adults.

BACKGROUND: The amygdala is highly implicated in an array of psychiatric disorders but is not accessible using currently available noninvasive neuromodulatory techniques. Low-intensity transcranial focused ultrasound (TFUS) is a neuromodulatory technique that has the capability of reaching subcortical regions noninvasively. METHODS: We studied healthy older adult participants (N = 21, ages 48-79 years) who received TFUS targeting the right amygdala and left entorhinal cortex (active control region) using a 2-visit within-participant crossover design. Before and after TFUS, behavioral measures were collected via the State-Trait Anxiety Inventory and an emotional reactivity and regulation task utilizing neutral and negatively valenced images from the International Affective Picture System. Heart rate and self-reported emotional valence and arousal were measured during the emotional reactivity and regulation task to investigate subjective and physiological responses to the task. RESULTS: Significant increases in both self-reported arousal in response to negative images and heart rate during emotional reactivity and regulation task intertrial intervals were observed when TFUS targeted the amygdala; these changes were not evident when the entorhinal cortex was targeted. No significant changes were found for state anxiety, self-reported valence to the negative images, cardiac response to the negative images, or emotion regulation. CONCLUSIONS: The results of this study provide preliminary evidence that a single session of TFUS targeting the amygdala may alter psychophysiological and subjective emotional responses, indicating some potential for future neuropsychiatric applications. However, more work on TFUS parameters and targeting optimization is necessary to determine how to elicit changes in a more clinically advantageous way

The Priority Structure of Bank Regulatory Capital: The Case of Subordinated Debt

The aftermath of a crisis often brings reflections on the adequacy of regulatory capital against financial shocks. Accordingly, succeeding regulatory interventions focus on strengthening the resilience of the banking system by improving the quality and quantity of capital, and subordinated debt (sub-debt) remains key to these reforms. Whether, however, the regulatory motive underpins the decision of banks to issue sub-debt is unclear. Moreover, the perceptions of shareholders on the regulatory function of sub-debt are less understood. This thesis attempts to answer these questions by first reviewing other roles of sub-debt then testing if regulation drives its issuance and finally revealing shareholder incentives that weaken its regulatory function. Contrasting capital requirement motives with other explanations, and accounting for equity issuance, we find that banks issue sub-debt primarily to improve their regulatory capital buffer. While a few non-regulatory factors, related to easier entry conditions to debt market, influence the issuance decision, their economic impact is smaller than the impact of the buffer. By exploring how variations in tail risk and size influence the sub-debt and equity issuance decisions by banks with low buffers, we show that issuance choices do not reflect risk-shifting incentives. Next, we review shareholders’ perceptions of the regulatory value of sub-debt vis-a-vis the risk-shifting and wealth-expropriation incentives associated with senior debt by comparing the reaction of stocks to these security announcements. We find that senior debt incentives are more valuable than the regulatory benefit of sub-debt. Contrary to regulatory expectations, announcement of sub-debt (capital-improving) offers are valueless even when undertaken by risky or less-capitalized banks; rather, senior debt offered by these vulnerable banks generate significant shareholder value. Pursuant to these risk-shifting motives, senior debt issuers get riskier post-issuance. These findings suggest that the broader debt priority structure harbours perverse incentives that dilute the regulatory effectiveness of sub-debt

Longitudinal changes in medial temporal cortical thickness in normal subjects with the APOE-4 polymorphism

People with the apolipoprotein-Eε4 (APOE-4) genetic risk for Alzheimer's disease show morphologic differences in medial temporal lobe regions when compared to non-carriers of the allele. Using a high-resolution MRI and cortical unfolding approach, our aim was to determine the rate of cortical thinning among medial temporal lobe subregions over the course of 2 years. We hypothesized that APOE-4 genetic risk would contribute to longitudinal cortical thickness change in the subiculum and entorhinal cortex, regions preferentially susceptible to Alzheimer's disease related pathology. Thirty-two cognitively intact subjects, mean age 61 years, 16 APOE-4 carriers, 16 non-carriers, underwent baseline and follow-up MRI scans. Over this relatively brief interval, we found significantly greater cortical thinning in the subiculum and entorhinal cortex of APOE-4 carriers when compared to non-carriers of the allele. Average cortical thinning across all medial temporal lobe subregions combined was also significantly greater for APOE-4 carriers. This finding is consistent with the hypothesis that carrying the APOE-4 allele renders subjects at a higher risk for developing Alzheimer's disease

Proceedings of the Eighth Annual Deep Brain Stimulation Think Tank: Advances in Optogenetics, Ethical Issues Affecting DBS Research, Neuromodulatory Approaches for Depression, Adaptive Neurostimulation, and Emerging DBS Technologies

We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was founded in 2012 providing a space where clinicians, engineers, researchers from industry and academia discuss current and emerging DBS technologies and logistical and ethical issues facing the field. The emphasis is on cutting edge research and collaboration aimed to advance the DBS field. The Eighth Annual DBS Think Tank was held virtually on September 1 and 2, 2020 (Zoom Video Communications) due to restrictions related to the COVID-19 pandemic. The meeting focused on advances in: (1) optogenetics as a tool for comprehending neurobiology of diseases and on optogenetically-inspired DBS, (2) cutting edge of emerging DBS technologies, (3) ethical issues affecting DBS research and access to care, (4) neuromodulatory approaches for depression, (5) advancing novel hardware, software and imaging methodologies, (6) use of neurophysiological signals in adaptive neurostimulation, and (7) use of more advanced technologies to improve DBS clinical outcomes. There were 178 attendees who participated in a DBS Think Tank survey, which revealed the expansion of DBS into several indications such as obesity, post-traumatic stress disorder, addiction and Alzheimer’s disease. This proceedings summarizes the advances discussed at the Eighth Annual DBS Think Tank

Direct recordings of grid-like neuronal activity in human spatial navigation

Grid cells in the entorhinal cortex appear to represent spatial location via a triangular coordinate system. Such cells, which have been identified in rats, bats and monkeys, are believed to support a wide range of spatial behaviors. Recording neuronal activity from neurosurgical patients performing a virtual-navigation task, we identified cells exhibiting grid-like spiking patterns in the human brain, suggesting that humans and simpler animals rely on homologous spatial-coding schemes