Masaki Nishida

REM Sleep, Prefrontal Theta, and the Consolidation of Human Emotional Memory

Both emotion and sleep are independently known to modulate declarative memory. Memory can be facilitated by emotion, leading to enhanced consolidation across increasing time delays. Sleep also facilitates offline memory processing, resulting in superior recall the next day. Here we explore whether rapid eye movement (REM) sleep, and aspects of its unique neurophysiology, underlie these convergent influences on memory. Using a nap paradigm, we measured the consolidation of neutral and negative emotional memories, and the association with REM-sleep electrophysiology. Subjects that napped showed a consolidation benefit for emotional but not neutral memories. The No-Nap control group showed no evidence of a consolidation benefit for either memory type. Within the Nap group, the extent of emotional memory facilitation was significantly correlated with the amount of REM sleep and also with right-dominant prefrontal theta power during REM. Together, these data support the role of REM-sleep neurobiology in the consolidation of emotional human memories, findings that have direct translational implications for affective psychiatric and mood disorders.

A Role for REM Sleep in Recalibrating the Sensitivity of the Human Brain to Specific Emotions

Although the impact of sleep on cognitive function is increasingly well established, the role of sleep in modulating affective brain processes remains largely uncharacterized. Using a face recognition task, here we demonstrate an amplified reactivity to anger and fear emotions across the day, without sleep. However, an intervening nap blocked and even reversed this negative emotional reactivity to anger and fear while conversely enhancing ratings of positive (happy) expressions. Most interestingly, only those subjects who obtained rapid eye movement (REM) sleep displayed this remodulation of affective reactivity for the latter 2 emotion categories. Together, these results suggest that the evaluation of specific human emotions is not static across a daytime waking interval, showing a progressive reactivity toward threat-related negative expressions. However, an episode of sleep can reverse this predisposition, with REM sleep depotentiating negative reactivity toward fearful expressions while concomitantly facilitating recognition and ratings of reward-relevant positive expressions. These findings support the view that sleep, and specifically REM neurophysiology, may represent an important factor governing the optimal homeostasis of emotional brain regulation.

Sleep-dependent facilitation of episodic memory details.

While a role for sleep in declarative memory processing is established, the qualitative nature of this consolidation benefit, and the physiological mechanisms mediating it, remain debated. Here, we investigate the impact of sleep physiology on characteristics of episodic memory using an item- (memory elements) and context- (contextual details associated with those elements) learning paradigm; the latter being especially dependent on the hippocampus. Following back-to-back encoding of two word lists, each associated with a different context, participants were assigned to either a Nap-group, who obtained a 120-min nap, or a No Nap-group. Six hours post-encoding, participants performed a recognition test involving item-memory and context-memory judgments. In contrast to item-memory, which demonstrated no between-group differences, a significant benefit in context-memory developed in the Nap-group, the extent of which correlated both with the amount of stage-2 NREM sleep and frontal fast sleep-spindles. Furthermore, a difference was observed on the basis of word-list order, with the sleep benefit and associated physiological correlations being selective for the second word-list, learned last (most proximal to sleep). These findings suggest that sleep may preferentially benefit contextual (hippocampal-dependent) aspects of memory, supported by sleep-spindle oscillations, and that the temporal order of initial learning differentially determines subsequent offline consolidation.

Theta oscillation in the human anterior cingulate cortex during all-night sleep: An electrocorticographic study

Ten epileptic patients each with subdural electrodes surgically attached to the anterior cingulate cortex (ACC; two cases), the orbitofrontal cortex (OFC; seven cases), or both (one case) were included in this study. We recorded each patients ACC or OFC electrocorticogram (ECoG) during the time period that the patient was awake and naturally asleep. We performed a Fast Fourier Transformation (FFT) power spectral analysis on each ECoG to examine its frequency component. We found that the ACC showed regular and continuous theta oscillation (5-7Hz) during wakefulness and rapid eye movement (REM) sleep, but not during slow wave sleep. Theta waves observed in REM sleep were not as distinct as those found in wakefulness. We also discovered that the orbitofrontal signals represented spectral peaks in the theta band only during wakefulness. This suggests the coexistence of theta oscillation in the ACC. Considering our previous observations of gamma and beta oscillations in the human hippocampus, we hypothesize that the human limbic system manifests two oscillatory activities. The results obtained in this study suggest that electrophysiological activity in the ACC could be related to particular psychological functions in wakefulness and in REM sleep. These results are useful in elucidating the human brain mechanism.

High frequency activities in the human orbitofrontal cortex in sleep-wake cycle

We recorded human orbitofrontal electrocorticogram during wakefulness and sleep in epileptic patients using subdural electrodes. During wakefulness and rapid eye movement (REM) sleep, we observed beta activity in the raw orbitofrontal signals. Power spectral analysis demonstrated beta enhancement during wakefulness and REM sleep when compared to slow wave sleep (SWS). During the phasic REM periods, the beta power was significantly lower than during the tonic REM periods. Gamma enhancement manifested itself in four out of six subjects during the phasic periods. This study is the first that has focused on electrical activity in the human orbitofrontal cortex. Although the role of the orbitofrontal cortex during sleep still remains unclear, high frequency activities give us important suggestions in elucidating the human sleep mechanism.

Slow sleep spindle and procedural memory consolidation in patients with major depressive disorder.

Introduction Evidence has accumulated, which indicates that, in healthy individuals, sleep enhances procedural memory consolidation, and that sleep spindle activity modulates this process. However, whether sleep-dependent procedural memory consolidation occurs in patients medicated for major depressive disorder remains unclear, as are the pharmacological and physiological mechanisms that underlie this process. Methods Healthy control participants (n=17) and patients medicated for major depressive disorder (n=11) were recruited and subjected to a finger-tapping motor sequence test (MST; nondominant hand) paradigm to compare the averaged scores of different learning phases (presleep, postsleep, and overnight improvement). Participants’ brain activity was recorded during sleep with 16 electroencephalography channels (between MSTs). Sleep scoring and frequency analyses were performed on the electroencephalography data. Additionally, we evaluated sleep spindle activity, which divided the spindles into fast-frequency spindle activity (12.5–16 Hz) and slow-frequency spindle activity (10.5–12.5 Hz). Result Sleep-dependent motor memory consolidation in patients with depression was impaired in comparison with that in control participants. In patients with depression, age correlated negatively with overnight improvement. The duration of slow-wave sleep correlated with the magnitude of motor memory consolidation in patients with depression, but not in healthy controls. Slow-frequency spindle activity was associated with reduction in the magnitude of motor memory consolidation in both groups. Conclusion Because the changes in slow-frequency spindle activity affected the thalamocortical network dysfunction in patients medicated for depression, dysregulated spindle generation may impair sleep-dependent memory consolidation. Our findings may help to elucidate the cognitive deficits that occur in patients with major depression both in the waking state and during sleep.

Impulse response function based on multivariate AR model can differentiate focal hemisphere in temporal lobe epilepsy

The purpose of this study is to propose and investigate a new approach for discriminating between focal and non-focal hemispheres in intractable temporal lobe epilepsy, based on applying multivariate time series analysis to the discharge-free background brain activity observed in nocturnal electrocorticogram (ECoG) time series. Five unilateral focal patients and one bilateral focal patient were studied. In order to detect the location of epileptic foci, linear multivariate autoregressive (MAR) models were fitted to the ECoG data; as a new approach for the purpose of summarizing these models in a single relevant parameter, the behavior of the corresponding impulse response functions was studied and described by an attenuation coefficient. In the majority of unilateral focal patients, the averaged attenuation coefficient was found to be almost always significantly larger in the focal hemisphere, as compared to the non-focal hemisphere. Also the amplitude of the fluctuations of the attenuation coefficient was significantly larger in the focal hemisphere. Moreover, in one patient showing a typical regular sleep cycle, the attenuation coefficient in the focal hemisphere tended to be larger during REM sleep and smaller during Non-REM sleep. In the bilateral focal patient, no statistically significant distinction between the hemispheres was found. This study provides encouraging results for new investigations of brain dynamics by multivariate parametric modeling. It opens up the possibility of relating diseases like epilepsy to the properties of inconspicuous background brain dynamics, without the need to record and analyze epileptic seizures or other evidently pathological waveforms.

Topographical distribution of fast and slow sleep spindles in medicated depressive patients

Purpose: To compare the properties of sleep spindles between healthy subjects and medicated patients with major depressive episode, including frequency range, spectra power, and spatial distribution of spindle power. Methods: Continuous 16-channel EEG was used to record nocturnal sleep in healthy control subjects and medicated depressive patients. Recordings were analyzed for changes in EEG power spectra and power topography. Additionally, we graphically demonstrated the pattern of spatial distribution of each type of sleep spindle, divided into fast (12.5–14 Hz) and slow spindles (11–12.5 Hz). Results: Sleep EEG records of depressive subjects exhibited a significantly higher amplitude of slow spindles in the prefrontal region, compared with the healthy controls (P < 0.01). Fast spindles were dominant in the centroparietal region in both depressive patients and the control group. Enhanced slow spindles in the prefrontal region were observed in the medicated depressive patients and not in the healthy controls. The frequency of fast spindles in depressive patients was globally higher than that in healthy participants. Conclusions: The alteration in sleep spindles seen in medicated depressive subjects may reflect a pharmacological modulation of synaptic function involving the thalamic-reticular and thalamocortical mechanisms.

Unilateral hippocampal infarction associated with an attempted suicide: a case report

IntroductionIn our case report we describe the case of a patient who experienced a stroke in her left hippocampus that was found following an attempted suicide via glyphosate overdose. To the best of our knowledge this is the first case report to describe a hippocampal infarction associated with a drug overdose.Case presentationA 64-year-old Japanese woman was brought to our emergency department after ingestion of an unknown dose of glyphosate surfactant herbicide in order to attempt suicide. On admission, she was assumed to be presenting with depression or psychiatric illness, however, sudden-onset memory deficit became apparent. The patient manifested delirium, confusion, and severe anxiety. In addition, short-term memory loss was prominent, with the patient forgetting her attempted suicide. Following an array of standard tests and a brain computed tomography scan (which only showed an old infraction), we performed a magnetic resonance imaging scan and neuropsychological evaluations. The brain magnetic resonance image revealed a small high-intensity lesion in the dorsal part of the left hippocampal body, and memory tests demonstrated severe short-term recall deficits. We diagnosed her with a left hippocampal infarction and administered a course of 75mg of clopidogrel. She gradually became less confused over the course of a week, and a follow-up memory test revealed partial improvement in some domains. No abnormalities were found on a follow-up brain scan. However, despite rehabilitation, memory impairments remain.ConclusionsIt is important to note that had the symptom of short-term memory been absent or less severe, she might have been misdiagnosed with depression or another psychiatric illness. Although a computed tomography scan failed to detect hippocampal lesions, a diffusion-weighted magnetic resonance imaging scan clearly revealed a lesion within the left hippocampus. Therefore, in addition to assessments focusing on psychiatric illnesses that might be the root cause of an attempted suicide, organic factors should be considered along with radiological examination and precise memory assessments for diagnosing similar cases.

Relation between Parametric Change of the Workload and Prefrontal Cortex Activity during a Modified Version of the 'Rock, Paper, Scissors' Task

Background/Aims: Modified rock, paper, scissors (RPS) tasks have previously been used in neuroscience to investigate activity of the prefrontal cortex (PFC). In this study, we investigated hemodynamic changes in the PFC using near-infrared spectroscopy (NIRS) during a modified RPS task in which each subjects successful performance rate was equalized; the workload was increased parametrically in order to reveal the resulting pattern of PFC activation. Methods: The subjects were 20 healthy adults. During RPS, the player uses hand gestures to represent rock, paper, and scissors. Rock beats scissors, paper beats rock, and scissors beats paper. In the modified RPS task, the player is instructed to lose intentionally against the computer hand; the computer goes first and the player follows. The interstimulus interval (ISI) level was adjusted with 11 steps. If the level rose, the ISI decreased and the workload increased parametrically. The maximal level (maxLv: the shortest ISI and the biggest workload) in which a subject could perform the task correctly was determined for every subject during rehearsal of the task prior to the experiment. Lowering the level from the maxLv made the task easier. Hemodynamic changes were measured by NIRS over 4 task levels (maxLv-3, maxLv-2, maxLv-1 and maxLv). Results: The hemodynamic changes in the left lateral PFC and bilateral Brodmann area 6 rose significantly with the increase in workload and presented a linear trend. Conclusion: These results suggest that PFC activation may linearly increase with increased workload during a modified RPS task in which successful performance rates of subjects are equalized.