Michael C. Chen

Michael C. Chen
PureTech Health

PhD

About

35
Publications
6,401
Reads
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2,450
Citations
Introduction
PureTech Health; Sonde Health; Harvard Medical School - Beth Israel Deaconess Medical Center
Additional affiliations
October 2012 - November 2015
Beth Israel Deaconess Medical Center
Position
  • PostDoc Position
November 2004 - June 2006
Yale University
Position
  • Research Assistant
September 2006 - September 2012
Stanford University
Position
  • PhD Student
Education
September 2006 - September 2012
Stanford University
Field of study
September 2002 - June 2006
Yale University
Field of study

Publications

Publications (35)
Article
Interaction between the basal ganglia and the cortex plays a critical role in a range of behaviors. Output from the basal ganglia to the cortex is thought to be relayed through the thalamus, but an intriguing alternative is that the basal ganglia may directly project to and communicate with the cortex. We explored an efferent projection from the gl...
Article
Full-text available
Sleep and wakefulness are promoted not by a single neural pathway but via wake or sleep-promoting nodes distributed across layers of the brain. We equate each layer with a brain region in proposing a layered subsumption model for arousal based on a computational architecture. Beyond the brainstem the layers include the diencephalon (hypothalamus, t...
Article
Full-text available
The midbrain dopamine system via the dorsal and ventral striatum regulates a wide range of behaviors. To dissect the role of dopaminergic projections to the dorsal striatum (nigrostriatal projection) and ventral striatum (mesolimbic projection) in sleep–wake behavior, we selectively chemogenetically stimulated nigrostriatal or mesolimbic projection...
Article
Objectives The National Sleep Foundation (NSF) sought to test, refine, and add statistical rigor to its previously described provisional Sleep Satisfaction Tool (SST). The tool assesses the general population's sleep satisfaction. Design In 2017, NSF created a provisional tool through systematic literature review and an expert consensus panel proc...
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Full-text available
In this study we uncovered, through targeted ablation, a potential role for corticospinal, cerebello-rubro-spinal, and hypothalamic A11 dopaminergic systems in the development of restless legs syndrome (RLS)-like movements during sleep. Targeted lesions in select basal ganglia (BG) structures also revealed a major role for nigrostriatal dopamine, t...
Article
Objectives: The goal of this project was to provisionally identify the basic elements of sleep satisfaction within the general population. Methods: The National Sleep Foundation conducted a systematic literature review and identified 495 published articles evaluating potential indicators of sleep satisfaction. The National Sleep Foundation then...
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Discrete populations of neurons at multiple levels of the brainstem control rapid eye movement (REM) sleep and the accompanying loss of postural muscle tone, or atonia. The specific contributions of these brainstem cell populations to REM sleep control remains incompletely understood. Here we show in rats that viral vector-based lesions of the vent...
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Full-text available
Human and animal studies have identified an especially critical role for the brainstem parabrachial (PB) complex in regulating electrocortical (electroencephalogram [EEG]) and behavioral arousal: lesions of the PB complex produce a monotonous high-voltage, slow-wave EEG and eliminate spontaneous behaviors. We report here that targeted chemogenetic...
Article
Rapid eye movement (REM) sleep is a recurring part of the sleep-wake cycle characterized by fast, desynchronized rhythms in the electroencephalogram (EEG), hippocampal theta activity, rapid eye movements, autonomic activation, and loss of postural muscle tone (atonia). The brain circuitry governing REM sleep is located in the pontine and medullary...
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The basal ganglia, a network of subcortical structures, play a critical role in movements, sleep and mental behavior. Basal ganglia disorders such as Parkinson’s disease and Huntington’s disease affect sleep. Deep brain stimulation (DBS) to treat motor symptoms in Parkinson’s disease can ameliorate sleep disturbances. Our series of previous studies...
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Full-text available
The role of specific cortical regions in sleep-regulating circuits is unclear. The anterior insula (AI) has strong reciprocal connectivity with wake and sleep-promoting hypothalamic and brainstem regions, and we hypothesized that the AI regulates patterns of sleep and wakefulness. To test this hypothesis, we lesioned the AI in rats (n = 8) and comp...
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The neural substrate of sleep homeostasis is unclear, but both cortical and subcortical structures are thought to be involved in sleep regulation. To test whether prior neuronal activity in the cortex or in subcortical regions drives sleep rebound, we systemically administered atropine (100 mg/kg) to rats, producing a dissociated state with slow-wa...
Article
Our recent study indicates that the lesions of the prefrontal cortex in rats result in depressive-like behavior in forced swim test and REM sleep alterations, two well-established biomarkers of depression disorder. We hypothesized that antidepressants may target the PFC to reverse depression. Systemic injections of antidepressants: the tricyclic an...
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Full-text available
Lesions of the globus pallidus externa (GPe) produce a profound sleep loss (∼45%) in rats, suggesting that GPe neurons promote sleep. As GPe neuronal activity is enhanced by dopamine (DA) from the substantia nigra pars compacta (SNc), we hypothesized that SNc DA via the GPe promotes sleep. To test this hypothesis, we selectively destroyed the DA af...
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Full-text available
Assessing neural commonalities and differences among depression, anxiety and their comorbidity is critical in developing a more integrative clinical neuroscience and in evaluating currently debated categorical vs dimensional approaches to psychiatric classification. Therefore, in this study, we sought to identify patterns of anomalous neural respon...
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Full-text available
The cerebral cortex and basal ganglia (BG) form a neural circuit that is disrupted in disorders such as Parkinson's disease. We found that neuronal activity (c-Fos) in the BG followed cortical activity, i.e., high in arousal state and low in sleep state. To determine if cortical activity is necessary for BG activity, we administered atropine to rat...
Article
Rapid eye movement (REM) sleep in mammals is associated with wakelike cortical and hippocampal activation and concurrent postural muscle atonia. Research during the past 5 decades has revealed the details of the neural circuitry regulating REM sleep and muscle atonia during this state. REM-active glutamatergic neurons in the sublaterodorsal nucleus...
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Background: Major depressive disorder (MDD) is characterized by abnormalities in structure, function, and connectivity in several brain regions. Few studies have examined how these regions are organized in the brain or investigated network-level structural aberrations that might be associated with depression. Methods: We used graph analysis to e...
Article
Recent research detailing the intrinsic functional organization of the brain provides a unique and useful framework to gain a better understanding of the neural bases of Major Depressive Disorder (MDD). In this review, we first present a brief history of neuroimaging research that has increased our understanding of the functional macro-architecture...
Article
Rapid eye movement (REM) sleep behavior disorder (RBD) is a failure of the circuitry regulating motor atonia during REM sleep. In REM sleep, neurons of the sublaterodorsal tegmental nucleus (SLD) project to interneurons in the ventromedial medulla (VMM) and spinal cord that in turn inhibit spinal motoneurons. In RBD, degeneration of this circuitry...
Article
Recent resting-state fMRI studies have shown that the apparent functional connectivity (FC) between brain regions may undergo changes on time-scales of seconds to minutes, the basis and importance of which are largely unknown. Here, we examine the electrophysiological correlates of within-scan FC variations during a condition of eyes-closed rest. A...
Article
A range of prefrontal and subcortical volumetric abnormalities have been found in adults and adolescents with bipolar disorder. It is unclear, however, if these deficits are present early in the onset of mania or are a consequence of multiple mood episodes or prolonged exposure to medication. The goal of this study was to examine whether youth with...
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Full-text available
Despite advances in neurobiological research on Major Depressive Disorder and Social Anxiety Disorder, little is known about the neural functioning of individuals with comorbid depression/social anxiety. We examined the timing of neural responses to social stress in individuals with major depression and/or social anxiety. We hypothesized that havin...
Article
Depression is characterized by sleep difficulties, but the extent to which subjective and objective sleep disturbances precede depression are unclear. This study was designed to examine perceptions of sleep quality in addition to actigraphy- and diary-measured sleep variables in healthy girls at low and high familial risk for major depressive disor...
Article
Sleep disturbance is an early marker for bipolar disorder (BD) onset in youth. We characterized sleep quality in adolescents experiencing mania within the last 6-12 months. We examined the association between mood and sleep in 27 adolescents with BD and 24 matched healthy controls (HC). Subjects were assessed by parent and teen report of sleep, a s...
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Researchers have documented that the hippocampus is smaller in individuals with depression than in those without. The temporal or causal association of this reduction in hippocampal volume in depression, however, is not known. To test the hypothesis that reduced hippocampal volume precedes and therefore may be implicated in the onset of depression....
Article
Major Depressive Disorder (MDD) is one of the most prevalent and costly of all psychiatric disorders. The hypothalamic pituitary adrenal (HPA)-axis, which regulates the hormonal response to stress, has been found to be disrupted in depression. HPA dysregulation may represent an important risk factor for depression. To examine a possible genetic und...
Article
Central nervous system plasticity is essential for normal function, but can also reinforce abnormal network behavior, leading to epilepsy and other disorders. The role of altered ion channel expression in abnormal plasticity has not been thoroughly investigated. Nav1.6 is the most abundantly expressed sodium channel in the nervous system. Because o...

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