Novelty preferences and cocaine-associated cues influence regions associated with the salience network in juvenile female rats.

Preferences for novel environments (novelty-seeking) is a risk factor for addiction, with little known about its underlying circuitry. Exposure to drug cues facilitates addiction maintenance, leading us to hypothesize that exposure to a novel environment activates a shared neural circuitry. Stimulation of the D1 receptor in the prelimbic cortex increases responsivity to drug-associated environments. Here, we use D1 receptor overexpression in the prelimbic cortex to probe brain responses to novelty-preferences (in a free-choice paradigm) and cocaine-associated odors following place conditioning. These same cocaine-conditioned odors were used to study neural circuitry with Blood Oxygen Level Dependent (BOLD) activity. D1 overexpressing females had deactivated BOLD signals related to novelty-preferences within the insula cortex and amygdala and activation in the frontal cortex and dopamine cell bodies. BOLD responses to cocaine cues were also sensitive to D1. Control females demonstrated a place preference for cocaine environments with no significant BOLD response, while D1 overexpressing females demonstrated a place aversion and weak BOLD responses to cocaine-conditioned odor cues within the insula cortex. For comparison, we provide data from an earlier study with juvenile males overexpressing D1 that show a strong preference for cocaine and elevated BOLD responses. The results support the use of a pharmacological manipulation (e.g., D1 overexpression) to probe the neural circuitry downstream from the prelimbic cortex.

Association of Prepubertal and Postpubertal Exposure to Childhood Maltreatment With Adult Amygdala Function.

Importance: Abnormalities in amygdala response to threatening faces have been observed in anxiety disorders, autism, bipolar disorder, depression, posttraumatic stress disorder, and schizophrenia. Abnormally hyperactive and hypoactive responses have typically been associated with anxiety and inhibition vs risk taking and inappropriate social behaviors. Maltreatment is a major risk factor for most of these disorders and is associated with abnormal amygdala function. Objective: To identify the type and age of exposure to childhood maltreatment that are associated with hyperactive and hypoactive amygdala responses in young adulthood. Design, Setting, and Participants: Data collection for this retrospective cohort study took place from November 8, 2010, to August 23, 2012. Data analyses were conducted from September 20, 2012, to June 27, 2018. Participants were recruited from the urban and suburban Boston vicinity without diagnostic restrictions based on exposure history. Exposures: The Maltreatment and Abuse Chronology of Exposure (MACE) scale was used to retrospectively assess type and age of exposure to childhood maltreatment. Main Outcomes and Measures: Activation and pattern information functional magnetic resonance imaging were used to assess bilateral amygdala response to angry and fearful faces vs neutral faces or shapes, and sensitive exposure periods were identified using cross-validated artificial intelligence predictive analytics (50 averaged randomized iterations with training on 63.3% and testing on 36.7% of the sample). Results: Of the 202 participants (mean [SD] age, 23.2 [1.7] years; 118 [58.4%] female), 52 (25.7%) reported no exposure to maltreatment and 150 (74.3%) reported exposure to 1 or more maltreatment types. Eight participants (15.1%) with a MACE score of 0 and 51 (34.2%) with a MACE score of 1 or higher had a history of major depression (odds ratio, 2.40; 95% CI, 1.05-6.06; P = .03); 8 unexposed participants (15.1%) and 46 with MACE scores of 1 or higher (30.9%) had a history of 1 or more anxiety disorders (odds ratio, 2.45; 95% CI, 1.03-6.50; P = .03). Retrospective self-report of physical maltreatment between 3 and 6 years of age and peer emotional abuse at 13 and 15 years were associated with amygdala activation to emotional faces vs shapes. Early exposure was associated with blunted response (ß = -0.17, P < .001), whereas later exposure was associated with augmented response (ß = 0.16, P < .001). Prepubertal vs postpubertal maltreatment was associated with an opposite response on the voxelwise response pattern in clustering stimuli of the same type (eg, mean [SD] emotional ellipse areas for physical maltreatment at age 4 years vs nonverbal emotional abuse at 13 years: 1.41 [1.05] vs 0.25 [0.10], P < .001) and in distinguishing between stimuli of different types (eg, mean [SD] emotional vs neutral faces distance for peer emotional abuse at age 6 years vs 13 years: 1.89 [0.75] vs 0.80 [0.39], P < .001). Conclusions and Relevance: The findings suggest that prepubertal vs postpubertal developmental differences in the association between maltreatment and amygdala response to threatening or salient stimuli exist. Understanding the role of adversity in different sensitive exposure periods and the potential adaptive significance of attenuated vs enhanced amygdala response may help explain why maltreatment may be a risk factor for many different disorders and foster creation of targeted interventions to preempt the emergence of psychopathology in at-risk youths.

Sustained opioid antagonism modulates striatal sensitivity to baby schema in opioid use disorder.

BACKGROUND: Chronic opioid misuse is associated with reduced sensitivity to natural rewards and social motivation deficits that include impaired caregiving. The neurobiological mechanisms underlying these deficits and their response to treatment are not well understood. Baby schema (Kindchenschema) is a set of juvenile physical features, which is perceived as "cute" and triggers motivation for caregiving. Recent studies suggest that the "baby schema effect" is mediated by the brain "reward" network. We studied the impact of opioid antagonist treatment on the baby schema response in patients with opioid use disorder. METHODS: Forty-seven (24 F) recently detoxified patients with opioid use disorder underwent functional magnetic resonance imaging (fMRI) while viewing infant portraits that were parametrically manipulated for baby schema content and rating them for cuteness, at baseline and during treatment with the injectable extended release opioid antagonist naltrexone (XRNTX). The study was not placebo-controlled. RESULTS: The behavioral effect of baby schema, indexed by "cuteness" ratings, was present and unaffected by XRNTX. The brain response to baby schema was absent at baseline, but present in the bilateral ventral striatum after two weeks of XRNTX treatment. The decline in self-reported craving for opioids was positively correlated with the brain fMRI response to baby schema in the bilateral ventral striatum. CONCLUSIONS: Opioid antagonist treatment modulated the brain reward system response to a marker of caregiving motivation in patients with opioid use disorder. Neural response to baby schema may offer a novel probe of social motivation and affiliative behaviors in this population.

Strength of baseline inter-trial correlations forecasts adaptive capacity in the vestibulo-ocular reflex.

Individual differences in sensorimotor adaptability may permit customized training protocols for optimum learning. Here, we sought to forecast individual adaptive capabilities in the vestibulo-ocular reflex (VOR). Subjects performed 400 head-rotation steps (400 trials) during a baseline test, followed by 20 min of VOR gain adaptation. All subjects exhibited mean baseline VOR gain of approximately 1.0, variable from trial to trial, and showed desired reductions in gain following adaptation with variation in extent across individuals. The extent to which a given subject adapted was inversely proportional to a measure of the strength and duration of baseline inter-trial correlations (ß). ß is derived from the decay of the autocorrelation of the sequence of VOR gains, and describes how strongly correlated are past gain values; it thus indicates how much the VOR gain on any given trial is informed by performance on previous trials. To maximize the time that images are stabilized on the retina, the VOR should maintain a gain close to 1.0 that is adjusted predominantly according to the most recent error; hence, it is not surprising that individuals who exhibit smaller ß (weaker inter-trial correlations) also exhibited the best adaptation. Our finding suggests that the temporal structure of baseline behavioral data contains important information that may aid in forecasting adaptive capacities. This has significant implications for the development of personalized physical therapy protocols for patients, and for other cases when it is necessary to adjust motor programs to maintain movement accuracy in response to pathological and environmental changes.

Repair of Physiologic Time Series: Replacement of Anomalous Data Points to Preserve Fractal Exponents.

Extraction of fractal exponents via the slope of the power spectrum is common in the analysis of many physiological time series. The fractal structure thus characterized is a manifestation of long-term correlations, for which the temporal order of the sample values is crucial. However, missing data points due to artifacts and dropouts are common in such data sets, which can seriously disrupt the computation of fractal parameters. We evaluated a number of methods for replacing missing data in time series to enable reliable extraction of the fractal exponent and make recommendations as to the preferred replacement method depending on the proportion of missing values and any a priori estimate of the fractal exponent.

Improved low-cost, MR-compatible olfactometer to deliver tobacco smoke odor.

We describe a low-cost, MRI-compatible olfactometer that delivers fresh cigarette smoke odor, a challenging odorant to present, as well as other odorants. This new olfactometer retains all of the advantages of an earlier design that was capable of only delivering volatile odors (Lowen & Lukas, Behavior Research Methods, 38, 307-313, 2006). The new system incorporates a novel switching mechanism that allows it to deliver fresh smoke generated from a burning cigarette during a stimulus presentation paradigm that might be employed in a cue-reactivity experiment. An evaluation study established that the olfactometer reliably delivered smoke to the participants and that tobacco smoke was discriminated from other odorants; there were no adverse reactions to the device.

Targeting modulates audiences' brain and behavioral responses to safe sex video ads.

Video ads promoting condom use are a key component of media campaigns to stem the HIV epidemic. Recent neuroimaging studies in the context of smoking cessation, point to personal relevance as one of the key variables that determine the effectiveness of public health messages. While minority men who have sex with men (MSM) are at the highest risk of HIV infection, most safe-sex ads feature predominantly Caucasian actors in heterosexual scenarios. We compared brain respons of 45 African American MSM to safe sex ads that were matched (i.e. 'Targeted') to participants' sexual orientation and race, and 'Untargeted' ads that were un matched for these characteristics. Ad recall, perceived 'convincingness' and attitudes towards condom use were also assessed. We found that Targeted ads were better remembered than the Untargeted ads but perceived as equally convincing. Targeted ads engaged brain regions involved in self-referential processing and memory, including the amygdala, hippocampus, temporal and medial prefrontal cortices (MPFC) and the precuneus. Connectivity between MPFC and precuneus and middle temporal gyrus was stronger when viewing Targeted ads. Our results suggest that targeting may increase cognitive processing of safe sex ads and justify further prospective studies linking brain response to media public health interventions and clinical outcomes.

Mood dysregulation and affective instability in emerging adults with childhood maltreatment: An ecological momentary assessment study.

Childhood maltreatment increases risk for mood, anxiety, substance use and personality disorders and is associated with alterations in structure, function and connectivity of brain regions involved in emotional regulation. We sought to assess whether maltreatment was specifically associated with disturbances in positive or negative mood regulation. Ecological momentary ratings were collected with a wristwatch-like device with joy-stick (Seiko ecolog) approximately six times per day over a week in 60 unmedicated participants (22 control, 38 maltreated, 18-25 years old). Forty-five percent of maltreated subjects had a history of major depression but all were currently euthymic. Principal component analysis with varimax rotation was used to provide orthogonal measures of positive and negative valence, which were analyzed for indices of variability, circadian rhythmicity and persistence, using linear and non-linear hierarchical modeling and Hurst analysis. Groups did not differ in mean levels of positive or negative affect. Maltreated subjects had increased variability and circadian and hemicircadian abnormalities in ratings of positive but not negative affect. Conversely, they had higher estimated Hurst exponents for negative but not positive affect ratings indicating a greater degree of persistence. Abnormalities in variability, rhythmicity and persistence were present in both maltreated subjects with and without histories of major depression. These findings suggest that both positive and negative valence systems may be dysregulated in individuals with childhood maltreatment. However the nature of the dysregulation appears to differ fundamentally in these domains, as positive mood ratings were more variable and negative ratings more persistent.

Emotional reaction facilitates the brain and behavioural impact of graphic cigarette warning labels in smokers.

BACKGROUND: Warning labels on cigarette packages are an important venue for information about the hazards of smoking. The 2009 US Family Smoking Prevention and Tobacco Control Act mandated replacing the current text-only labels with graphic warning labels. However, labels proposed by the Food and Drug Administration (FDA) were challenged in court by the tobacco companies, who argued successfully that the proposed labels needlessly encroached on their right to free speech, in part because they included images of high emotional salience that indiscriminately frightened rather than informed consumers. METHODS: We used functional MRI to examine the effects of graphic warning labels' emotional salience on smokers' brain activity and cognition. Twenty-four smokers viewed a random sequence of blocks of graphic warning labels that have been rated high or low on an 'emotional reaction' scale in previous research. RESULTS: We found that labels rated high on emotional reaction were better remembered, associated with reduction in the urge to smoke, and produced greater brain response in the amygdala, hippocampi, inferior frontal gyri and the insulae. CONCLUSIONS: Recognition memory and craving are, respectively, correlates of effectiveness of addiction-related public health communications and interventions, and amygdala activation facilitates the encoding of emotional memories. Thus, our results suggest that emotional reaction to graphic warning labels contributes to their public health impact and may be an integral part of the neural mechanisms underlying their effectiveness. Given the urgency of the debate about the constitutional risks and public health benefits of graphic warning labels, these preliminary findings warrant consideration while longitudinal clinical studies are underway.

Cocaine-conditioned odor cues without chronic exposure: Implications for the development of addiction vulnerability.

Adolescents are highly vulnerable to addiction and are four times more likely to become addicted at first exposure than at any other age. The dopamine D1 receptor, which is typically overexpressed in the normal adolescent prefrontal cortex, is involved in drug cue responses and is associated with relapse in animal models. In human drug addicts, imaging methods have detected increased activation in response to drug cues in reward- and habit-associated brain regions. These same methods can be applied more quantitatively to rodent models. Here, changes in neuronal activation in response to cocaine-conditioned cues were observed using functional magnetic resonance imaging in juvenile rats that were made to over-express either D1 receptors or green fluorescent protein by viral-mediated transduction. Reduced activation was observed in the amygdala and dopamine cell body regions in the low cue-preferring/control juvenile rats in response to cocaine cues. In contrast, increased activation was observed in the dorsal striatum, nucleus accumbens, prefrontal cortex, and dopamine cell bodies in high cue-preferring/D1 juveniles. The increase in cue salience that is mediated by increased D1 receptor density, rather than excessive cocaine experience, appears to underlie the transition from aversion to reward in cue-induced neural response and may form the basis for habit-forming vulnerability.

Effects of citalopram and escitalopram on fMRI response to affective stimuli in healthy volunteers selected by serotonin transporter genotype.

This study was designed to assess whether functional magnetic resonance imaging (fMRI) following antidepressant administration (pharmaco-fMRI) is sufficiently sensitive to detect differences in patterns of activation between enantiomers of the same compound. Healthy adult males (n=11) participated in a randomized, double-blind, cross-over trial with three medication periods during which they received citalopram (racemic mixture), escitalopram (S-citalopram alone), or placebo for 2 weeks. All participants had high expression serotonin transporter genotypes. An fMRI scan that included passive viewing of overt and covert affective faces and affective words was performed after each medication period. Activation in response to overt faces was greater following escitalopram than following citalopram in the right insula, thalamus, and putamen when the faces were compared with a fixation stimulus. For the rapid covert presentation, a greater response was observed in the left middle temporal gyrus in the happy versus fearful contrast following escitalopram than following citalopram. Thus, the combination of genomics and fMRI was successful in discriminating between two very similar drugs. However, the pattern of activation observed suggests that further studies are indicated to understand how to optimally combine the two techniques.

Extended-release naltrexone (XR-NTX) attenuates brain responses to alcohol cues in alcohol-dependent volunteers: a bold FMRI study.

Oral naltrexone reduces heavy drinking, but is less consistent as an abstinence promoter, whereas once-monthly extended-release naltrexone (XR-NTX) also maintains abstinence. The present study sought to determine if alcohol cue reactivity is attenuated by XR-NTX. Twenty-eight detoxified alcohol-dependent adult male and female volunteers received a single i.m. injection of either XR-NTX or placebo under double-blind conditions. An fMRI/cue reactivity procedure was conducted immediately before and two weeks after injection. At baseline, alcohol-related visual and olfactory cues elicited significant increases in orbital and cingulate gyri, inferior frontal and middle frontal gyri. Subsequently, brain activation was significantly altered in XR-NTX-treated individuals. These affected brain regions are associated with the integration of emotion, cognition, reward, punishment, and learning/memory, suggesting that XR-NTX attenuates the salience of alcohol-related cues. Such an effect on brain function may interrupt the processes associated with "slips" and relapse, which may account for XR-NTX's ability to maintain abstinence.

Brain structural abnormalities in Doberman pinschers with canine compulsive disorder.

Obsessive compulsive disorder (OCD) is a debilitating condition, the etiology of which is poorly understood, in part because it often remains undiagnosed/untreated for a decade or more. Characterizing the etiology of compulsive disorders in animal models may facilitate earlier diagnosis and intervention. Doberman pinschers have a high prevalence of an analogous behavioral disorder termed canine compulsive disorder (CCD), which in many cases responds to treatments used for OCD. Thus, studies of CCD may help elucidate the etiology of compulsive disorders. We compared brain structure in Dobermans with CCD (N=8) and unaffected controls (N=8) to determine whether CCD is associated with structural abnormalities comparable to those reported in humans with OCD. We obtained 3 Tesla magnetic resonance structural and diffusion images from anesthetized Dobermans and subjected images to segmentation, voxel based morphometry, and diffusion tensor analyses. CCD dogs exhibited higher total brain and gray matter volumes and lower dorsal anterior cingulate cortex and right anterior insula gray matter densities. CCD dogs also had higher fractional anisotropy in the splenium of the corpus callosum, the degree of which correlated with the severity of the behavioral phenotype. Together, these findings suggest that CCD is associated with structural abnormalities paralleling those identified in humans with OCD. Accordingly, the CCD model, which has a number of advantages over other animal models of OCD, may assist in establishing the neuroanatomical basis for and etiology of compulsive disorders, which could lead to earlier diagnosis of and new treatments for humans and animals with these disorders.

The hypnotic zolpidem increases the synchrony of BOLD signal fluctuations in widespread brain networks during a resting paradigm.

Networks of brain regions having synchronized fluctuations of the blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) time-series at rest, or "resting state networks" (RSNs), are emerging as a basis for understanding intrinsic brain activity. RSNs are topographically consistent with activity-related networks subserving sensory, motor, and cognitive processes, and studying their spontaneous fluctuations following acute drug challenge may provide a way to understand better the neuroanatomical substrates of drug action. The present within-subject double-blind study used BOLD fMRI at 3T to investigate the functional networks influenced by the non-benzodiazepine hypnotic zolpidem (Ambien). Zolpidem is a positive modulator of γ-aminobutyric acid(A) (GABA(A)) receptors, and engenders sedative effects that may be explained in part by how it modulates intrinsic brain activity. Healthy participants (n=12) underwent fMRI scanning 45 min after acute oral administration of zolpidem (0, 5, 10, or 20mg), and changes in BOLD signal were measured while participants gazed at a static fixation point (i.e., at rest). Data were analyzed using group independent component analysis (ICA) with dual regression and results indicated that compared to placebo, the highest dose of zolpidem increased functional connectivity within a number of sensory, motor, and limbic networks. These results are consistent with previous studies showing an increase in functional connectivity at rest following administration of the positive GABA(A) receptor modulators midazolam and alcohol, and suggest that investigating how zolpidem modulates intrinsic brain activity may have implications for understanding the etiology of its powerful sedative effects.

Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation.

Zolpidem is a short-acting imidazopyridine hypnotic that binds at the benzodiazepine binding site on specific GABA(A) receptors to enhance fast inhibitory neurotransmission. The behavioral and receptor pharmacology of zolpidem has been studied extensively, but little is known about its neuronal substrates in vivo. In the present within-subject, double-blind, and placebo-controlled study, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) at 3 Tesla was used to assess the effects of zolpidem within the brain. Healthy participants (n=12) were scanned 60 min after acute oral administration of zolpidem (0, 5, 10, or 20mg), and changes in BOLD signal were measured in the visual cortex during presentation of a flashing checkerboard. Heart rate and oxygen saturation were monitored continuously throughout the session. Zolpidem (10 and 20mg) reduced the robust visual system activation produced by presentation of this stimulus, but had no effects on physiological activity during the fMRI scan. Zolpidem's modulation of the BOLD signal within the visual cortex is consistent with the abundant distribution of GABA(A) receptors localized in this region, as well as previous studies showing a relationship between increased GABA-mediated neuronal inhibition and a reduction in BOLD activation.

fMRI brain activation during a delay discounting task in HIV-positive adults with and without cocaine dependence.

Cocaine use is associated with poorer HIV clinical outcomes and may contribute to neurobiological impairments associated with impulsive decision making. This study examined the effect of cocaine dependence on brain activation during a delay discounting task involving choices between smaller immediate rewards and larger delayed ones. Participants were 39 HIV-positive adults on antiretroviral therapy who had current cocaine dependence ("active," n=15), past cocaine dependence ("recovered," n=13), or no lifetime substance dependence ("naïve," n=11). Based on responses on a traditional delay discounting task, three types of choices were individualized for presentation during functional magnetic resonance imaging: hard (similarly valued), easy (disparately valued), and no (single option). Active participants had significantly smaller increases in activation than naïve participants during hard versus easy choices bilaterally in the precentral gyrus and anterior cingulate cortex and in the right frontal pole (including dorsolateral, ventrolateral, and orbitofrontal cortex). During hard and easy choices relative to no choices, active participants had smaller increases in activation compared to naïve participants in frontoparietal cortical regions. These deficits in the executive network during delay discounting choices may contribute to impulsive decision making among HIV-positive cocaine users, with implications for risk behaviors associated with disease transmission and progression.

Differential effects of acute cocaine and placebo administration on visual cortical activation in healthy subjects measured using BOLD fMRI.

Many blood oxygenation level dependent (BOLD) functional magnetic resonance imaging studies have shown a strong response due to cocaine in brain regions with high concentrations of dopamine receptors. However, cocaine also has non-specific effects, including cardiovascular changes that may cause changes in BOLD signals, raising the possibility that measured changes could be due to these non-specific effects. The following experiment was conducted to address this concern. Subjects were given either cocaine or saline infusions during a long BOLD functional magnetic resonance imaging study. A flashing uniform-field stimulus, periodically alternating between on and off, provided a strong activation of primary visual cortex. There was a significant main effect of drug between cocaine and placebo. Although we did not demonstrate a significant drug x time interaction, BOLD signal changes associated with visual stimulation appeared unchanged after cocaine administration, whereas the signal differences appeared to decrease during placebo. Explanation of the differential response between the two groups may reflect cocaine expectancy instead of a direct effect of cocaine on BOLD signal changes but will require further investigation to fully elucidate.

A low-cost, MR-compatible olfactometer.

We present a design for an olfactometer, suitable for fMRI experiments, that can be constructed at extremely low cost. The olfactometer presents odors directly to the nose via a nasal cannula at unobtrusively low flow velocities, with no large assemblies required on or near the subject's face. The olfactometer can be controlled manually, or by computer via a serial interface. A validation study verified that the olfactometer reliably presents odors to test subjects. Errors and response latency times decreased with increased flow rate in an orderly manner, as expected.

Emotional task-dependent low-frequency fluctuations and methylphenidate: Wavelet scaling analysis of 1/f-type fluctuations in fMRI of the cerebellar vermis.

UNLABELLED: Ion channel currents, neural firing patterns, and brain BOLD signals display 1/f-type fluctuations or fractal properties in time. By design, fMRI methods attempt to minimize the contribution of variance from low-frequency physiological 1/f-noise. New fMRI methods are described to visualize and measure 1/f-type BOLD fluctuations in volunteers recalling affectively neutral or emotional memories or meditating (i.e., attending to breathing) then retrospectively rating emotional content. A wavelet scaling exponent (alpha) was used to characterize signals from 0.015625 to 0.5Hz in cerebellar lobules VIII to X of the vermis (posterior inferior vermis; PIV), a region coordinating balance, eye tracking, locomotion, and vascular tone, and a possible site of pathology in attention deficit hyperactivity disorder (ADHD). RESULTS: Changes in alpha and emotional measures were correlated in PIV voxels (r = 0.622, d.f .= 14, P < 0.0005), but not other regions examined. In contrast, conventional means and standard deviations of PIV voxels were unchanged. Methylphenidate, shown to decrease slow oscillations in rodent basal ganglia [Ruskin DN, Bergstrom DA, Shenker A, Freeman LE, Baek D, Walters JR. Drugs used in the treatment of attention-deficit/hyperactivity disorder affect postsynaptic firing rate and oscillation without preferential dopamine autoreceptor action. Biol Psychiatry 2001;49:340-50.], abolished task-dependent alpha changes in the PIV of an adult with ADHD. Wavelet analysis of long BOLD time series appears well suited to fractal physiology and studies of pharmacologically modulated cerebellar-thalamic-cortical function in ADHD or other psychiatric disorders.

Dynamics of sleep-wake cyclicity in developing rats.

Adult mammals cycle between periods of sleep and wakefulness. Recent assessments of these cycles in humans and other mammals indicate that sleep bout durations exhibit an exponential distribution, whereas wake bout durations exhibit a power-law distribution. Moreover, it was found that wake bout distributions, but not sleep bout distributions, exhibit scale invariance across mammals of different body sizes. Here we test the generalizability of these findings by examining the distributions of sleep and wake bout durations in infant rats between 2 and 21 days of age. In agreement with Lo et al., we find that sleep bout durations exhibit exponential distributions at all ages examined. In contrast, however, wake bout durations also exhibit exponential distributions at the younger ages, with a clear power-law distribution only emerging at the older ages. Further analyses failed to find substantial evidence either of short- or long-term correlations in the data, thus suggesting that the durations of current sleep and wake bouts evolve through time without memory of the durations of preceding bouts. These findings further support the notion that bouts of sleep and wakefulness are regulated independently. Moreover, in light of recent evidence that developmental changes in sleep and wake bouts can be attributed in part to increasing forebrain influences, these findings suggest the possibility of identifying specific neural circuits that modulate the changing complexity of sleep and wake dynamics during development.