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1.  Life-long consequences of juvenile exposure to psychotropic drugs on brain and behavior 
Progress in brain research  2014;211:13-30.
Psychostimulants such as methylphenidate (MPH) and antidepressants such as fluoxetine (FLX) are widely used in the treatment of various mental disorders or as cognitive enhancers. These medications are often combined, for example, to treat co-morbid disorders. There is a considerable body of evidence from animal models indicating that individually these psychotropic medications can have detrimental effects on brain and behavior, especially when given during sensitive periods of brain development. However, almost no studies investigate possible interactions between these drugs. This is surprising given that their combined neurochemical effects (enhanced dopamine and serotonin neurotransmission) mimic some effects of illicit drugs such as cocaine and amphetamine. Here we summarize recent studies in juvenile rats on the molecular effects in the mid- and forebrain and associated behavioral changes, after such combination treatments. Our findings indicate that these combined MPH+FLX treatments can produce similar molecular changes as seen after cocaine exposure, while inducing behavioral changes indicative of dysregulated mood and motivation, effects that often endure into adulthood.
doi:10.1016/B978-0-444-63425-2.00002-7
PMCID: PMC4331026  PMID: 24968775
3.  Molecular mechanisms of clinical concentrating and diluting disorders 
Progress in brain research  2008;170:539-550.
Impaired urinary dilution leading to water retention and hyponatremia may occur in patients with cardiac failure, cirrhosis, pregnancy, hypothyroidism, glucocorticoid and mineralocorticoid deficiency. The mechanisms for these defects predominantly involve the non-osmotic stimulation of arginine vasopressin release with upregulation of aquaporin 2 water channel expression and trafficking to the apical membrane of the principal cells of the collecting duct. These perturbations are reversed by V2 vasopressin receptor antagonists. In contrast, urinary concentration defects leading to polyuria are vasopressin-resistant. They may involve several factors, such as impaired counter-current concentration secondary to downregulation of Na-K-2Cl co-transporter. Vasopressin-resistant downregulation of aquaporin 2 expression has also been described as a factor in impaired urinary concentration.
doi:10.1016/S0079-6123(08)00441-X
PMCID: PMC4319677  PMID: 18655907
vasopressin; water channels; hyponatremia; V2 receptor antagonists; aquaretics
4.  Making the lifetime connection between brain and machine for restoring and enhancing function 
Progress in brain research  2011;194:1-25.
A reliable neural interface that lasts a lifetime will lead to the development of neural prosthetic devices as well as the possibility that brain function can be enhanced. Our data demonstrate that a reliable neural interface is best achieved when the surrounding neuropil grows into the electrode tip where it is held securely, allowing myelinated axons to be recorded using implanted amplifiers. Stable single and multiunits were recorded from three implanted subjects and classified according to amplitudes and firing rates. In one paralyzed and mute subject implanted for over 5 years with a double electrode in the speech motor cortex, the single units allowed recognition of over half the 39 English language phonemes detected using a variety of decoding methods. These single units were used by the subject in a speech task where vowel phonemes were recognized and fed back to the subject using audio output. Weeks of training resulted in an 80% success rate in producing four vowels in an adaptation of the classic center-out task used in motor control studies. The importance of using single units was shown in a different task using pure tones that the same subject heard and then sung or hummed in his head. Feedback was associated with smoothly coordinated unit firings. The plasticity of the unit firings was demonstrated over several sessions first without, and then with, feedback. These data suggest that units can be reliably recorded over years, that there is an inverse relationship between single unit firing rate and amplitude, that pattern recognition decoding paradigms can allow phoneme recognition, that single units appear more important than multiunits when precision is important, and that units are plastic in their functional relationships. These characteristics of a reliable neural interface are essential for the development of neural prostheses and also for the future enhancement of human brain function.
doi:10.1016/B978-0-444-53815-4.00020-0
PMCID: PMC4305334  PMID: 21867791
brain computer interfacing; brain machine interfacing; neurotrophic electrode; long-term human recording; speech prosthesis; single unit recording; multi-unit recording; local field potentials
5.  Cortical Plasticity, Excitatory–Inhibitory Balance, and Sensory Perception 
Progress in brain research  2013;207:65-90.
Experience shapes the central nervous system throughout life. Structural and functional plasticity confers a remarkable ability on the brain, allowing neural circuits to adequately adapt to dynamic environments. This process can require selective adjustment of many excitatory and inhibitory synapses in an organized manner, in such a way as to enhance representations of behaviorally important sensory stimuli while preserving overall network excitability. The rules and mechanisms that orchestrated these changes across different synapses and throughout neuronal ensembles are beginning to be understood. Here, we review the evidence connecting synaptic plasticity to functional plasticity and perceptual learning, focusing on the roles of various neuromodulatory systems in enabling plasticity of adult neural circuits. However, the challenge remains to appropriately leverage these systems and forms of plasticity to persistently improve perceptual abilities and behavioral performance.
doi:10.1016/B978-0-444-63327-9.00003-5
PMCID: PMC4300113  PMID: 24309251
neuromodulation; sensory cortex; synaptic plasticity; excitatory–inhibitory balance; perception
6.  Cortical Odor Processing in Health and Disease 
Progress in brain research  2014;208:275-305.
The olfactory system has a rich cortical representation, including a large archicortical component present in most vertebrates, and in mammals neocortical components including the entorhinal and orbitofrontal cortices. Together, these cortical components contribute to normal odor perception and memory. They help transform the physicochemical features of volatile molecules inhaled or exhaled through the nose into the perception of odor objects with rich associative and hedonic aspects. This chapter focuses on how olfactory cortical areas contribute to odor perception and begins to explore why odor perception is so sensitive to disease and pathology. Odor perception is disrupted by a wide range of disorders including Alzheimer’s disease, Parkinson’s disease, schizophrenia, depression, autism, and early life exposure to toxins. This olfactory deficit often occurs despite maintained functioning in other sensory systems. Does the unusual network of olfactory cortical structures contribute to this sensitivity?
doi:10.1016/B978-0-444-63350-7.00011-5
PMCID: PMC4284974  PMID: 24767487
piriform cortex; orbitofrontal cortex; entorhinal cortex; mediodorsal thalamus; odor perception
7.  Consensus for tinnitus patient assessment and treatment outcome measurement: Tinnitus Research Initiative meeting, Regensburg, July 2006 
Progress in brain research  2007;166:525-536.
There is widespread recognition that consistency between research centres in the ways that patients with tinnitus are assessed and outcomes following interventions are measured would facilitate more effective co-operation and more meaningful evaluations and comparisons of outcomes. At the first Tinnitus Research Initiative meeting held in Regensburg in July 2006 an attempt was made through workshops to gain a consensus both for patient assessments and for outcome measurements. It is hoped that this will contribute towards better cooperation between research centres in finding and evaluating treatments for tinnitus by allowing better comparability between studies.
doi:10.1016/S0079-6123(07)66050-6
PMCID: PMC4283806  PMID: 17956816
tinnitus; standards; assessment; questionnaires; treatment; outcome; case history
8.  Affective brain areas and sleep disordered breathing 
Progress in brain research  2014;209:275-293.
The neural damage accompanying the hypoxia, reduced perfusion, and other consequences of sleep-disordered breathing found in obstructive sleep apnea, heart failure (HF), and congenital central hypoventilation syndrome (CCHS), appears in areas that serve multiple functions, including emotional drives to breathe, and involve systems that serve affective, cardiovascular, and breathing roles. The damage, assessed with structural magnetic resonance imaging (MRI) procedures, shows tissue loss or water content and diffusion changes indicative of injury, and impaired axonal integrity between structures; damage is preferentially unilateral. Functional MRI responses in affected areas also are time- or amplitude- distorted to ventilatory or autonomic challenges. Among the structures injured are the insular, cingulate, and ventral medial prefrontal cortices, as well as cerebellar deep nuclei and cortex, anterior hypothalamus, raphé, ventrolateral medulla, basal ganglia and, in CCHS, the locus coeruleus. Raphé and locus coeruleus injury may modify serotonergic and adrenergic modulation of upper airway and arousal characteristics. Since both axons and gray matter show injury, the consequences to function, especially to autonomic, cognitive, and mood regulation, are major. Several affected rostral sites, including the insular and cingulate cortices and hippocampus, mediate aspects of dyspnea, especially in CCHS, while others, including the anterior cingulate and thalamus, participate in initiation of inspiration after central breathing pauses, and the medullary injury can impair baroreflex and breathing control. The ancillary injury associated with sleep-disordered breathing to central structures can elicit multiple other distortions in cardiovascular, cognitive, and emotional functions in addition to effects on breathing regulation.
doi:10.1016/B978-0-444-63274-6.00014-X
PMCID: PMC4060533  PMID: 24746053
Obstructive Sleep Apnea; Congenital Central Hypoventilation Syndrome; Heart Failure; Hypothalamus; Medulla; Brainstem; Magnetic Resonance Imaging; Dyspnea
9.  Coding odor identity and odor value in awake rodents 
Progress in brain research  2014;208:205-222.
In the last decade, drastic changes in the understanding of the role of the olfactory bulb and piriform cortex in odor detection have taken place through awake behaving recording in rodents. It is clear that odor responses in mitral and granule cells are strikingly different in the olfactory bulb of anesthetized vs. awake animals. In addition, sniff recording has evidenced that mitral cell responses to odors during the sniff can convey information on the odor identity and sniff phase. Moreover, we review studies that show that the mitral cell conveys not only information on odor identity but also on whether the odor is rewarded or not (odor value). Finally, we discuss how the substantial increase in awake behaving recording raises questions for future studies.
doi:10.1016/B978-0-444-63350-7.00008-5
PMCID: PMC4131676  PMID: 24767484
olfaction; awake behaving; anesthetized; sniff; olfactory bulb; piriform cortex
10.  Convergence of pattern generator outputs on a common mechanism of diaphragm motor unit recruitment 
Progress in brain research  2014;209:309-329.
Motor units are the final element of neuromotor control. In manner analogous to the organization of neuromotor control in other skeletal muscles, diaphragm motor units comprise phrenic motoneurons located in the cervical spinal cord that innervate the diaphragm muscle, the main inspiratory muscle in mammals. Diaphragm motor units play a primary role in sustaining ventilation, but are also active in other non-ventilatory behaviors, including coughing, sneezing, vomiting, defecation and parturition. Diaphragm muscle fibers comprise all fiber types. Thus, diaphragm motor units display substantial differences in contractile and fatigue properties, but importantly properties of the motoneuron and muscle fibers within a motor unit are matched. As in other skeletal muscles, diaphragm motor units are recruited in order such that motor units that display greater fatigue resistance are recruited earlier and more often than more fatigable motor units. The properties of the motor unit population are critical determinants of the function of a skeletal muscle across the range of possible motor tasks. Accordingly, fatigue-resistant motor units are sufficient to generate the forces necessary for ventilatory behaviors whereas more fatigable units are only activated during expulsive behaviors important for airway clearance. Neuromotor control of diaphragm motor units may reflect selective inputs from distinct pattern generators distributed according to the motor unit properties necessary to accomplish these different motor tasks. In contrast, widely-distributed inputs to phrenic motoneurons from various pattern generators (e.g., for breathing, coughing or vocalization) would dictate recruitment order based on intrinsic electrophysiological properties.
doi:10.1016/B978-0-444-63274-6.00016-3
PMCID: PMC4154308  PMID: 24746055
Ventilation; respiratory muscles; inspiration; motor unit; diaphragm muscle
11.  Cognitive Neuroscience of Sleep 
Progress in brain research  2010;185:1-19.
Mechanism is at the heart of understanding, and this chapter addresses underlying brain mechanisms and pathways of cognition and the impact of sleep on these processes, especially those serving learning and memory. This chapter reviews the current understanding of the relationship between sleep/waking states and cognition from the perspective afforded by basic neurophysiological investigations. The extensive overlap between sleep mechanisms and the neurophysiology of learning and memory processes provide a foundation for theories of a functional link between the sleep and learning systems. Each of the sleep states, with its attendant alterations in neurophysiology, is associated with facilitation of important functional learning and memory processes. For rapid eye movement (REM) sleep, salient features such as PGO waves, theta synchrony, increased acetylcholine, reduced levels of monoamines and, within the neuron, increased transcription of plasticity-related genes, cumulatively allow for freely occurring bidirectional plasticity (long-term potentiation (LTP) and its reversal, depotentiation). Thus, REM sleep provides a novel neural environment in which the synaptic remodeling essential to learning and cognition can occur, at least within the hippocampal complex. During nonREM sleep Stage 2 spindles, the cessation and subsequent strong bursting of noradrenergic cells and coincident reactivation of hippocampal and cortical targets would also increase synaptic plasticity, allowing targeted bidirectional plasticity in the neocortex as well. In delta nonREM sleep, orderly neuronal reactivation events in phase with slow wave delta activity, together with high protein synthesis levels, would facilitate the events that convert early LTP to long lasting LTP. Conversely, delta sleep does not activate immediate early genes associated with de novo LTP. This nonREM sleep-unique genetic environment combined with low acetylcholine levels may serve to reduce the strength of cortical circuits that activate in the ~50% of delta-coincident reactivation events that do not appear in their waking firing sequence. The chapter reviews the results of manipulation studies, typically total sleep or REM sleep deprivation, that serve to underscore the functional significance of the phenomenological associations. Finally, the implications of sleep neurophysiology for learning and memory will be considered from a larger perspective in which the association of specific sleep states with both potentiation or depotentiation is integrated into mechanistic models of cognition.
doi:10.1016/B978-0-444-53702-7.00001-4
PMCID: PMC4180265  PMID: 21075230
Bidirectional plasticity; Long Term Potentiation (LTP); depotentiation; Spindles; Theta; Slow Waves; Acetylcholine (ACh); Norepinephrine (NE); Serotonin (5HT); Memory Consolidation
12.  Persistent neural activity in the prefrontal cortex: a mechanism by which BDNF regulates working memory? 
Progress in brain research  2008;169:251-266.
Working memory is the ability to maintain representations of task-relevant information for short periods of time to guide subsequent actions or make decisions. Neurons of the prefrontal cortex exhibit persistent firing during the delay period of working memory tasks. Despite extensive studies, the mechanisms underlying this persistent neural activity remain largely obscure. The neurotransmitter systems of dopamine, NMDA, and GABA have been implicated, but further investigations are necessary to establish their precise roles and relationships. Recent research has suggested a new component: brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, TrkB. We review the research on persistent activity and suggest that BDNF/TrkB signaling in a distinct class of interneurons plays an important role in organizing persistent neural activity at the single-neuron and network levels.
doi:10.1016/S0079-6123(07)00015-5
PMCID: PMC4163787  PMID: 18394479
TrkB; neurotrophins; plateau potentials; parvalbumin; interneurons; dopamine; ACh; GABA
13.  Dimensional reduction in sensorimotor systems: A framework for understanding muscle coordination of posture 
Progress in brain research  2007;165:299-321.
The simple act of standing up is an important and essential motor behavior that most humans and animals achieve with ease. Yet, maintaining standing balance involves complex sensorimotor transformations that must continually integrate a large array of sensory inputs and coordinate multiple motor outputs to muscles throughout the body. Multiple, redundant local sensory signals are integrated to form an estimate of a few global, task-level variables important to postural control, such as body center of mass position and body orientation with respect to Earth-vertical. Evidence suggests that a limited set of muscle synergies, reflecting preferential sets of muscle activation patterns, are used to move task variables such as center of mass position in a predictable direction following a postural perturbations.
We propose a hierarchal feedback control system that allows the nervous system the simplicity of performing goal-directed computations in task-variable space, while maintaining the robustness afforded by redundant sensory and motor systems. We predict that modulation of postural actions occurs in task-variable space, and in the associated transformations between the low-dimensional task-space and high-dimensional sensor and muscle spaces. Development of neuromechanical models that reflect these neural transformations between low and high-dimensional representations will reveal the organizational principles and constraints underlying sensorimotor transformations for balance control, and perhaps motor tasks in general. This framework and accompanying computational models could be used to formulate specific hypotheses about how specific sensory inputs and motor outputs are generated and altered following neural injury, sensory loss, or rehabilitation.
doi:10.1016/S0079-6123(06)65019-X
PMCID: PMC4121431  PMID: 17925254
Muscle; balance; EMG; muscle synergy; motor control; biomechanics; feedback; sensorimotor integration
14.  Cerebellar and Prefrontal Cortex Contributions to Adaptation, Strategies, and Reinforcement Learning 
Progress in brain research  2014;210:217-253.
Traditionally, motor learning has been studied as an implicit learning process, one in which movement errors are used to improve performance in a continuous, gradual manner. The cerebellum figures prominently in this literature given well-established ideas about the role of this system in error-based learning and the production of automatized skills. Recent developments have brought into focus the relevance of multiple learning mechanisms for sensorimotor learning. These include processes involving repetition, reinforcement learning, and strategy utilization. We examine these developments, considering their implications for understanding cerebellar function and how this structure interacts with other neural systems to support motor learning. Converging lines of evidence from behavioral, computational, and neuropsychological studies suggest a fundamental distinction between processes that use error information to improve action execution or action selection. While the cerebellum is clearly linked to the former, its role in the latter remains an open question.
doi:10.1016/B978-0-444-63356-9.00009-1
PMCID: PMC4118688  PMID: 24916295
cerebellum; prefrontal cortex; basal ganglia; sensorimotor learning; adaptation; reinforcement learning; systems interaction; error-based learning; ataxia
15.  Biological and social influences on cognitive control processes dependent on prefrontal cortex 
Progress in brain research  2011;189:319-339.
Cognitive control functions (“executive functions” [EFs] such as attentional control, self-regulation, working memory, and inhibition) that depend on prefrontal cortex (PFC) are critical for success in school and in life. Many children begin school lacking needed EF skills. Disturbances in EFs occur in many mental health disorders, such as ADHD and depression. This chapter addresses modulation of EFs by biology (genes and neurochemistry) and the environment (including school programs) with implications for clinical disorders and for education. Unusual properties of the prefrontal dopamine system contribute to PFC’s vulnerability to environmental and genetic variations that have little effect elsewhere. EFs depend on a late-maturing brain region (PFC), yet they can be improved even in infants and preschoolers, without specialists or fancy equipment. Research shows that activities often squeezed out of school curricula (play, physical education, and the arts) rather than detracting from academic achievement help improve EFs and enhance academic outcomes. Such practices may also head off problems before they lead to diagnoses of EF impairments, including ADHD. Many issues are not simply education issues or health issues; they are both.
doi:10.1016/B978-0-444-53884-0.00032-4
PMCID: PMC4103914  PMID: 21489397
executive functions; self-regulation; dopamine; COMT; interventions; dopamine transporter; ADHD; gender difference
16.  Imaging dopamine neurotransmission in live human brain 
Progress in brain research  2014;211:165-182.
Dopamine is an important regulator of cognition and behavior, but its precise influence on human brain processing remains unclear because of the lack of a reliable technique to study dopamine in the live human brain. In the recent years, a number of techniques have been developed to detect, map, and measure dopamine released during task performance. Most of these techniques are based on molecular imaging methods and have varying degrees of sensitivity. We developed a single-scan dynamic molecular imaging technique for the detection of dopamine released during task performance in the live human brain. This technique is extremely sensitive and has test–retest reliability. Using this technique, we detected dopamine released during the processing of a number of cognitive, behavioral, and emotional tasks. Since this technique acquires data that cannot be obtained using any other techniques, it extends the scope of neuroimaging research.
doi:10.1016/B978-0-444-63425-2.00007-6
PMCID: PMC4085579  PMID: 24968780
dopamine; molecular imaging; raclopride; fallypride; cognition; behavior; emotion; attention-deficit hyperactivity disorder
17.  A Cognitive Framework for Understanding and Improving Interference Resolution in the Brain 
Progress in brain research  2013;207:351-377.
All of us are familiar with the negative impact of interference on achieving our task goals. We are referring to interference by information, which either impinges on our senses from an external environmental source or is internally generated by our thoughts. Informed by more than a decade of research on the cognitive and neural processing of interference, we have developed a framework for understanding how interference impacts our neural systems and especially how it is regulated and suppressed during efficient on-task performance. Importantly, externally and internally generated interferences have distinct neural signatures, and further, distinct neural processing emerges depending on whether individuals must ignore and suppress the interference, as for distractions, or engage with them in a secondary task, as during multitasking. Here, we elaborate on this cognitive framework and how it changes throughout the human lifespan, focusing mostly on research evidence from younger adults and comparing these findings to data from older adults, children, and cognitively impaired populations. With insights gleaned from our growing understanding, we then describe three novel translational efforts in our lab directed at improving distinct aspects of interference resolution using cognitive training. Critically, these training approaches were specifically developed to target improved interference resolution based on neuroplasticity principles and have shown much success in randomized controlled first version evaluations in healthy aging. Our results show not only on-task training improvements but also robust generalization of benefit to other cognitive control abilities. This research showcases how an in-depth understanding of neural mechanisms can then inform the development of effective deficit-targeted interventions, which can in turn benefit both healthy and cognitively impaired populations.
doi:10.1016/B978-0-444-63327-9.00013-8
PMCID: PMC4067257  PMID: 24309262
interference; distraction; multitasking; attention; cognitive control; cognitive training; neuroplasticity; aging
18.  Effects of Glycinergic Inhibition Failure on Respiratory Rhythm and Pattern Generation 
Progress in brain research  2014;209:25-38.
Inhibitory interactions between neurons of the respiratory network are involved in rhythm generation and pattern formation. Using a computational model of brainstem respiratory networks, we investigated the possible effects of suppressing glycinergic inhibition on the activity of different respiratory neuron types. Our study revealed that progressive suppression of glycinergic inhibition affected all neurons of the network and disturbed neural circuits involved in termination of inspiration. Causal was a dysfunction of postinspiratory inhibition targeting inspiratory neurons, which often led to irregular preterm reactivation of these neurons, producing double or multiple short-duration inspiratory bursts. An increasing blockade of glycinergic inhibition led to apneustic inspiratory activity. Similar disturbances of glycinergic inhibition also occur during hypoxia. A clear difference in prolonged hypoxia, however, is that the rhythm terminates in expiratory apnea. The critical function of glycinergic inhibition for normal respiratory rhythm generation and the consequences of its reduction, including in pathological conditions, are discussed.
doi:10.1016/B978-0-444-63274-6.00002-3
PMCID: PMC4065418  PMID: 24746041
computational modeling; respiratory rhythm; pre-Bötzinger complex; glycinergic inhibition; apneusis; apnea; hypoxia; translational medicine
19.  Rhythmic Bursting in the Pre-Bötzinger Complex: Mechanisms and Models 
Progress in brain research  2014;209:1-23.
The pre-Bötzinger complex (pre-BötC), a neural structure involved in respiratory rhythm generation, can generate rhythmic bursting activity in vitro that persists after blockade of synaptic inhibition. Experimental studies have identified two mechanisms potentially involved in this activity: one based on the persistent sodium current (INaP) and the other involving calcium (ICa) and/or calcium-activated nonspecific cation (ICAN) currents. In this modeling study, we investigated bursting generated in single neurons and excitatory neural populations with randomly distributed conductances of INaP and ICa. We analyzed the possible roles of these currents, the Na+/K+ pump, synaptic mechanisms, and network interactions in rhythmic bursting generated under different conditions. We show that a population of synaptically coupled excitatory neurons with randomly distributed INaP- and/or ICAN-mediated burst generating mechanisms can operate in different oscillatory regimes with bursting dependent on either current or independent of both. The existence of multiple oscillatory regimes and their state dependence may explain rhythmic activities observed in the pre-BötC under different conditions.
doi:10.1016/B978-0-444-63274-6.00001-1
PMCID: PMC4059190  PMID: 24746040
neural oscillations; respiration; persistent sodium current; calcium-activated nonspecific cation current; sodium–potassium pump
20.  Cardiorespiratory Coupling: Common Rhythms in Cardiac, Sympathetic, and Respiratory Activities 
Progress in brain research  2014;209:191-205.
Cardiorespiratory coupling is an encompassing term describing more than the well-recognized influences of respiration on heart rate and blood pressure. Our data indicate that cardiorespiratory coupling reflects a reciprocal interaction between autonomic and respiratory control systems, and the cardiovascular system modulates the ventilatory pattern as well. For example, cardioventilatory coupling refers to the influence of heart beats and arterial pulse pressure on respiration and is the tendency for the next inspiration to start at a preferred latency after the last heart beat in expiration. Multiple complementary, well-described mechanisms mediate respiration’s influence on cardiovascular function, whereas mechanisms mediating the cardiovascular system’s influence on respiration may only be through the baroreceptors but are just being identified. Our review will describe a differential effect of conditioning rats with either chronic intermittent or sustained hypoxia on sympathetic nerve activity but also on ventilatory pattern variability. Both intermittent and sustained hypoxia increase sympathetic nerve activity after 2 weeks but affect sympatho-respiratory coupling differentially. Intermittent hypoxia enhances sympatho-respiratory coupling, which is associated with low variability in the ventilatory pattern. In contrast, after constant hypobaric hypoxia, 1-to-1 coupling between bursts of sympathetic and phrenic nerve activity is replaced by 2-to-3 coupling. This change in coupling pattern is associated with increased variability of the ventilatory pattern. After baro-denervating hypobaric hypoxic-conditioned rats, splanchnic sympathetic nerve activity becomes tonic (distinct bursts are absent) with decreases during phrenic nerve bursts and ventilatory pattern becomes regular. Thus, conditioning rats to either intermittent or sustained hypoxia accentuates the reciprocal nature of cardiorespiratory coupling. Finally, identifying a compelling physiologic purpose for cardiorespiratory coupling is the biggest barrier for recognizing its significance. Cardiorespiratory coupling has only a small effect on the efficiency of gas exchange; rather, we propose that cardiorespiratory control system may act as weakly coupled oscillator to maintain rhythms within a bounded variability.
doi:10.1016/B978-0-444-63274-6.00010-2
PMCID: PMC4052709  PMID: 24746049
neural control of heart rate; neural control of sympathetic nerve activity; neural control of respiration; weakly coupled oscillators
21.  Assessment of genome and proteome profiles in cocaine abuse 
Progress in brain research  2006;158:173-195.
Until recently, knowledge of the impact of abuse drugs on gene and protein expression in the brain was limited to less than 100 targets. With the advent of high-throughput genomic and proteomic techniques investigators are now able to evaluate changes across the entire genome and across thousands of proteins in defined brain regions and generate expression profiles of vulnerable neuroanatomical substrates in rodent and non-human primate drug abuse models and in human post-mortem brain tissue from drug abuse victims. The availability of gene and protein expression profiles will continue to expand our understanding of the short- and long-term consequences of drug addiction and other addictive disorders and may provide new approaches or new targets for pharmacotherapeutic intervention. This chapter will review gene expression data from rodent, non-human primate and human post-mortem studies of cocaine abuse and will provide a preliminary proteomic profile of human cocaine abuse and explore how these studies have advanced our understanding of addiction.
doi:10.1016/S0079-6123(06)58009-4
PMCID: PMC4048548  PMID: 17027697
microarray; RNA amplification; gene expression; molecular fingerprint; qPCR; transcriptome; proteome; brain; post-mortem; monkey
22.  Decoding Speech for Understanding and Treating Aphasia 
Progress in brain research  2013;207:435-456.
Aphasia is an acquired language disorder with a diverse set of symptoms that can affect virtually any linguistic modality across both the comprehension and production of spoken language. Partial recovery of language function after injury is common but typically incomplete. Rehabilitation strategies focus on behavioral training to induce plasticity in underlying neural circuits to maximize linguistic recovery. Understanding the different neural circuits underlying diverse language functions is a key to developing more effective treatment strategies. This chapter discusses a systems identification analytic approach to the study of linguistic neural representation. The focus of this framework is a quantitative, model-based characterization of speech and language neural representations that can be used to decode, or predict, speech representations from measured brain activity. Recent results of this approach are discussed in the context of applications to understanding the neural basis of aphasia symptoms and the potential to optimize plasticity during the rehabilitation process.
doi:10.1016/B978-0-444-63327-9.00018-7
PMCID: PMC4043958  PMID: 24309265
aphasia; speech; language; neural encoding; decoding
23.  Functional Genomics and Psychiatric Illness 
Progress in brain research  2002;138:10.1016/S0079-6123(02)38087-7.
doi:10.1016/S0079-6123(02)38087-7
PMCID: PMC3843349  PMID: 12432779
24.  Modulation of the brain's functional network architecture in the transition from wake to sleep 
Progress in brain research  2011;193:10.1016/B978-0-444-53839-0.00018-1.
The transition from quiet wakeful rest to sleep represents a period over which attention to the external environment fades. Neuroimaging methodologies have provided much information on the shift in neural activity patterns in sleep, but the dynamic restructuring of human brain networks in the transitional period from wake to sleep remains poorly understood. Analysis of electrophysiological measures and functional network connectivity of these early transitional states shows subtle shifts in network architecture that are consistent with reduced external attentiveness and increased internal and self-referential processing. Further, descent to sleep is accompanied by the loss of connectivity in anterior and posterior portions of the default-mode network and more locally organized global network architecture. These data clarify the complex and dynamic nature of the transitional period between wake and sleep and suggest the need for more studies investigating the dynamics of these processes.
doi:10.1016/B978-0-444-53839-0.00018-1
PMCID: PMC3811144  PMID: 21854969
sleep; functional connectivity; graph theory; brain networks; alpha EEG; fMRI; EEG/fMRI
25.  The evolution of neocortex in primates 
Progress in brain research  2012;195:91-102.
We can learn about the evolution of neocortex in primates through comparative studies of cortical organization in primates and those mammals that are the closest living relatives of primates, in conjunction with brain features revealed by the skull endocasts of fossil archaic primates. Such studies suggest that early primates had acquired a number of features of neocortex that now distinguish modern primates. Most notably, early primates had an array of new visual areas, and those visual areas widely shared with other mammals had been modified. Posterior parietal cortex was greatly expanded with sensorimotor modules for reaching, grasping, and personal defense. Motor cortex had become more specialized for hand use, and the functions of primary motor cortex were enhanced by the addition and development of premotor and cingulate motor areas. Cortical architecture became more varied, and cortical neuron populations became denser overall than in nonprimate ancestors. Primary visual cortex had the densest population of neurons, and this became more pronounced in the anthropoid radiation. Within the primate clade, considerable variability in cortical size, numbers of areas, and architecture evolved.
doi:10.1016/B978-0-444-53860-4.00005-2
PMCID: PMC3787901  PMID: 22230624
prosimians; tarsiers; anthropoids; sensory cortex; motor cortex

Results 1-25 (115)