Bright light therapy and early morning attention, mathematical performance, electroencephalography and brain connectivity in adolescents with morning sleepiness.

Adolescents typically sleep too little and feel drowsy during morning classes. We assessed whether morning use of an LED bright light device could increase alertness in school students. Twenty-six (8M/18F) healthy, unmedicated participants, ages 13-18 years, (mean 17.1±1.4) were recruited following screenings to exclude psychopathology. Baseline assessments were made of actigraph-assessed sleep, attention, math solving ability, electroencephalography and structural and functional MRI (N = 10-11, pre-post). Participants nonrandomly received 3-4 weeks of bright light therapy (BLT) for 30 minutes each morning and used blue light blocking glasses for 2 hours before bedtime. BLT devices were modified to surreptitiously record degree of use so that the hypothesis tested was whether there was a significant relationship between degree of use and outcome. They were used 57±18% (range 23%-90%) of recommended time. There was a significant association between degree of use and: (1) increased beta spectral power in frontal EEG leads (primary measure); (2) greater post-test improvement in math performance and reduction in errors of omission on attention test; (3) reduced day-to-day variability in bed times, sleep onset, and sleep duration during school days; (4) increased dentate gyrus volume and (5) enhanced frontal connectivity with temporal, occipital and cerebellar regions during Go/No-Go task performance. BLT was associated with improvement in sleep cycle consistency, arousal, attention and functional connectivity, but not sleep onset or duration (primary measures). Although this was an open study, it suggests that use of bright morning light and blue light blocking glasses before bed may benefit adolescents experiencing daytime sleepiness. Clinical trial registration: Clinicaltrials.gov ID-NCT05383690.

Potential sensitive period effects of maltreatment on amygdala, hippocampal and cortical response to threat.

Childhood maltreatment is a leading risk factor for psychopathology, though it is unclear why some develop risk averse disorders, such as anxiety and depression, and others risk-taking disorders including substance abuse. A critical question is whether the consequences of maltreatment depend on the number of different types of maltreatment experienced at any time during childhood or whether there are sensitive periods when exposure to particular types of maltreatment at specific ages exert maximal effects. Retrospective information on severity of exposure to ten types of maltreatment during each year of childhood was collected using the Maltreatment and Abuse Chronology of Exposure scale. Artificial Intelligence predictive analytics were used to delineate the most important type/time risk factors. BOLD activation fMRI response to threatening versus neutral facial images was assessed in key components of the threat detection system (i.e., amygdala, hippocampus, anterior cingulate, inferior frontal gyrus and ventromedial and dorsomedial prefrontal cortices) in 202 healthy, unmedicated, participants (84 M/118 F, 23.2 ± 1.7 years old). Emotional maltreatment during teenage years was associated with hyperactive response to threat whereas early childhood exposure, primarily to witnessing violence and peer physical bullying, was associated with an opposite pattern of greater activation to neutral than fearful faces in all regions. These findings strongly suggest that corticolimbic regions have two different sensitive period windows of enhanced plasticity when maltreatment can exert opposite effects on function. Maltreatment needs to be viewed from a developmental perspective in order to fully comprehend its enduring neurobiological and clinical consequences.

Open assessment of the therapeutic and rate-dependent effects of brain balance center® and interactive metronome® exercises on children with attention deficit hyperactivity disorder.

The aim of this open study was to delineate domains of benefit and effect size measures to design an appropriately powered randomized control trial to assess the efficacy of Brain Balance@ exercises and Interactive Metronome@ training (BB/IM) on ADHD symptoms in children. Participants underwent an extensive 15-week, 5 time per week, at-home training program. Results were assessed in 16 youths with ADHD (14M/2F, 10.8±1.7 years) who completed the program and compared to 8 typically developing controls (4M/F4, 11.0±1.8 years). BB/IM was associated with a significant reduction of 8.3 and 8.2 points on the Conner's Parent Rating Scale - Revised and the ADHD Rating Scale - IV. BB/IM was not associated with improvement on the Quotient ADHD System but with rate-dependent effects on hyperactivity and attention that were similar to previously reported effects of low dose methylphenidate. Both therapeutic and rate-dependent effects were observed on the Tower of London. The study provides information that could be used to design a randomized control trial, which is required for proof of efficacy. A key limitation is that 59% of the 39 enrolled participants with ADHD dropped out of the study and a new study should include multiple ratings during the course of treatment.

Individual Differences in Hemispheric Emotional Valence by Computerized Test Correlate with Lateralized Differences in Nucleus Accumbens, Hippocampal and Amygdala Volumes.

Purpose: Conventional theories of hemispheric emotional valence (HEV) postulate fixed hemispheric differences in emotional processing. Schiffer's dual brain psychology proposes that there are prominent individual differences with a substantial subset showing a reversed laterality pattern. He further proposed that hemispheric differences were more akin to differences in personality than in emotional processing. This theory is supported by findings that unilateral treatments, such as transcranial magnetic stimulation, are effective if they accurately target individual differences in laterality. The aim of this paper was to assess if a computer test of hemispheric emotional valence (CTHEV) could effectively identify individual differences in HEV and to ascertain if these individual differences were associated with underlying differences in brain structure and connectivity. Patients and Methods: The CTHEV was administered to 50 (18 male/32 female) right-handed participants, aged 18-19 years, enrolled in a study assessing the neurobiological effects of childhood maltreatment. Based on a literature review, we determined whether CTHEV correlated with lateralized volumes of the nucleus accumbens, amygdala, hippocampus, and subgenual anterior cingulate as well as volume of the corpus callosum. Results: CTHEV scores correlated with laterality indices of the nucleus accumbens (p = 0.00016), amygdala (p = 0.0138) and hippocampus (p = 0.031). A positive left hemispheric valence was associated with a larger left-sided nucleus accumbens and hippocampus and a smaller left amygdala. We identified four eigenvector network centrality DTI measures that predict CTHEV, most notably the left amygdala, and found that CTHEV results correlated with total and segment-specific corpus callosal volumes. Conclusion: Individual differences in HEV can be readily assessed by computer test and correlate with differences in brain structure and connectivity that could provide a mechanistic understanding. These findings provide further support for a revised understanding of HEV and provide a tool that could be used to guide lateralized brain treatments.

Sex and sensitive period differences in potential effects of maltreatment on axial versus radial diffusivity in the corpus callosum.

Corpus callosum (CC) abnormalities have been observed in several psychiatric disorders. Maltreatment has also been associated with marked differences in CC anatomy and microstructure, though rarely controlled for in psychiatric neuroimaging studies. The aim of this study was to identify type and timing of maltreatment associated with alterations in CC microstructure and to ascertain if they differ by sex. T1 and diffusion-weighted MRIs were obtained from 345 (135 M/210 F) healthy 18-25-year-olds. The Maltreatment and Abuse Chronology of Exposure scale provided retrospective data on exposure to ten types of maltreatment across each year of childhood. AI predictive analytics were used to identify the most significant type and time risk factors. The most striking maltreatment-associated alterations in males were in axial diffusivity and were most specifically associated with exposure to emotional abuse or neglect during segment-specific sensitive periods. In contrast, maltreatment was associated with marked alteration in radial diffusivity and fractional anisotropy in females and was most specifically associated with early physical neglect during one common sensitive period involving all segments except the splenium. Overall sex differences, controlling for maltreatment, brain size, and sociodemographic factors were limited to the genu with greater fractional anisotropy in males and radial diffusivity in females. These findings suggest that maltreatment may target myelinization in females and axonal development in males and that these sex differences need to be taken into account in studies seeking to delineate the contribution of CC abnormalities and interhemispheric communication to psychiatric disorders.

Additional Insights into the Relationship Between Brain Network Architecture and Susceptibility and Resilience to the Psychiatric Sequelae of Childhood Maltreatment.

Childhood maltreatment is associated with increased risk for psychiatric and substance use disorders. However, some maltreated individuals appear resilient to these consequences while manifesting the same array of brain changes as maltreated individuals with psychopathology. Hence, a critical issue has been to identify compensatory brain alterations in these resilient individuals. We recently reported that maltreatment is associated with a more vulnerable structural brain network architecture. Resilient individuals have this same vulnerability but appeared to be able to effectively compensate due to reduced nodal efficiency (ability of a node to influence the global network) in 9 specific brain regions that moderate the relationship between maltreatment and psychopathology. Following up we now report that network vulnerability increases progressively during late adolescence to plateau at about 21 years of age, which may help to explain age of onset of psychopathology. Further, we found that network vulnerability was most significantly affected by parental verbal abuse between 16-18 years of age and number of types of maltreatment during childhood. Asymptomatic individuals with no history of psychopathology had more prominent alterations in nodal efficiency than asymptomatic individuals with prior history, who specifically showed reduced nodal efficiency in right amygdala and right subcallosal gyrus. Experiencing inadequate financial sufficiency during childhood increased risk of susceptibility versus resilience by 2.98-fold (95% CI 1.49-5.97, p = 0.002) after adjusting for differences in exposure to maltreatment. Interestingly, adequate-to-higher financial sufficiency appeared to be protective and was associated with reduced nodal efficiency in the right postcentral gyrus and subcallosal gyrus 'resilience' nodes.

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.

Quitting starts in the brain: a randomized controlled trial of app-based mindfulness shows decreases in neural responses to smoking cues that predict reductions in smoking.

Current treatments for smoking yield suboptimal outcomes, partly because of an inability to reduce cue-induced smoking. Mindfulness training (MT) has shown preliminary efficacy for smoking cessation, yet its neurobiological target remains unknown. Our prior work with nonsmokers indicates that MT reduces posterior cingulate cortex (PCC) activity. In individuals who smoke, the PCC, consistently a main hub of the "default mode network," activates in response to smoking cues. In this randomized controlled trial, we tested the effects of app-delivered MT on PCC reactivity to smoking cues and whether individual differences in MT-mediated PCC changes predicted smoking outcomes. Smoking cue-induced PCC reactivity was measured using functional magnetic resonance imaging at baseline and 1 month after receiving smartphone app-based MT (n = 33) vs. an active control (National Cancer Institute's QuitGuide, n = 34). Whether individual differences in treatment-related changes in PCC activity predicted smoking behavior was assessed. The MT group demonstrated a significant correlation between a reduction in PCC reactivity to smoking cues and a decline in cigarette consumption (r = 0.39, p = 0.02). No association was found in the control group (r = 0.08, p = 0.65). No effects of group alone were found in PCC or cigarette reduction. Post hoc analysis revealed this association is sex specific (women, r = 0.49, p = 0.03; men: r = -0.08, p = 0.79). This initial report indicates that MT specifically reduces smoking cue-induced PCC activity in a subject-specific manner, and the reduction in PCC activity predicts a concurrent decline in smoking. These findings link the hypothesized behavioral effects of MT for smoking to neural mechanisms particularly in women. This lays the groundwork for identifying individuals who may benefit from targeted digital therapeutic treatments such as smartphone-based MT, yielding improved clinical outcomes.

Susceptibility or Resilience to Maltreatment Can Be Explained by Specific Differences in Brain Network Architecture.

BACKGROUND: Childhood maltreatment is a major risk factor for psychopathology. However, some maltreated individuals appear remarkably resilient to the psychiatric effects while manifesting the same array of brain abnormalities as maltreated individuals with psychopathology. Hence, a critical aim is to identify compensatory brain alterations that enable resilient individuals to maintain mental well-being despite alterations in stress-susceptible regions. METHODS: Network models were constructed from diffusion tensor imaging and tractography in physically healthy unmedicated 18- to 25-year-old participants (N = 342, n = 192 maltreated) to develop network-based explanatory models. RESULTS: First, we determined that susceptible and resilient individuals had the same alterations in global fiber stream network architecture using two different definitions of resilience: 1) no lifetime history of Axis I or II disorders, and 2) no clinically significant symptoms of anxiety, depression, anger-hostility, or somatization. Second, we confirmed an a priori hypothesis that right amygdala nodal efficiency was lower in asymptomatic resilient than in susceptible participants or control subjects. Third, we identified eight other nodes with reduced nodal efficiency in resilient individuals and showed that nodal efficiency moderated the relationship between maltreatment and psychopathology. Fourth, we found that models based on global network architecture and nodal efficiency could delineate group membership (control, susceptible, resilient) with 75%, 82%, and 80% cross-validated accuracy. CONCLUSIONS: Together these findings suggest that sparse fiber networks with increased small-worldness following maltreatment render individuals vulnerable to psychopathology if abnormalities occur in specific nodes, but that decreased ability of certain nodes to propagate information throughout the network mitigates the effects and leads to resilience.

Nicotine normalizes cortico-striatal connectivity in non-smoking individuals with major depressive disorder.

Nicotine dependence and major depressive disorder (MDD) are highly comorbid, yet causal links between these prevalent disorders are unclear. One possible mechanism is that nicotine ameliorates MDD-related neurobiological dysfunction in specific networks. For instance, cortico-striatal circuitry is enhanced by nicotine, and such paths are disrupted in individuals with MDD. Specifically, MDD has been associated with reduced connectivity between the nucleus accumbens (NAc) and rostral anterior cingulate cortex (rACC) but enhanced connectivity between the dorsal striatum (DS) and dorsolateral prefrontal cortex (DLPFC). Determining whether nicotine normalizes these circuits in non-smokers with MDD may elucidate mechanisms underlying links between disorders. This was tested by administering placebo and a 2-mg dose of nicotine to unmedicated non-smokers with and without MDD prior to collecting resting-state functional magnetic imaging data using a cross-over design. On placebo, individuals with MDD showed significantly reduced NAc-rACC and a trend for enhanced DS-DLPFC functional connectivity relative to healthy controls. In MDD, acute nicotine administration normalized both pathways to the level of healthy controls, while having no impact on healthy controls. Nicotine's effects on NAc-rACC connectivity was influenced by anhedonia, consistent with the role of this network in reward and nicotine's ability to enhance reward deficiencies in MDD. These results indicate that nicotine normalizes dysfunctional cortico-striatal communication in unmedicated non-smokers with MDD. Nicotine's influence on these circuitries highlights a possible mechanism whereby individuals with MDD are more vulnerable to develop nicotine dependence. Findings suggest that nicotinic agents may have therapeutic effects on disrupted cortico-striatal connectivity.

Physical and biological roles of mesoscale eddies in Japanese eel larvae dispersal in the western North Pacific Ocean.

The physical and biological roles of mesoscale eddies in Japanese eel larvae dispersal are investigated using a three-dimensional (3D) particle-tracking method, with a focus on the Subtropical Counter Current eddies of the western North Pacific Ocean. Virtual eel larvae (v-larvae) movements depends on the 3D ocean currents and active swimming behavior, including vertical swimming (diel vertical migration), horizontal directional swimming toward settlement habitat, and horizontal swimming toward available food. V-larvae are able to remain in eddies passively due to mesoscale eddy nonlinearity and/or actively due to attraction to rich food supplies. Thus, both physical trapping and biological attraction to food contribute to the retention of v-larvae in eddies. Physical trapping dominates the retention of v-larvae whose swimming speeds are slower than the eddy propagation speed, whereas biological food attraction prevails in the retention of v-larvae swimming faster than eddy propagation. Food availability differs between warm (anti-cyclonic) and cold (cyclonic) eddies, with the latter providing a richer food supply. Fish larvae that are retained for longer durations in cold eddies (shorter durations in warm eddies) are able to obtain more food and potentially grow faster, which enhances survival rates.

Differential effects of childhood neglect and abuse during sensitive exposure periods on male and female hippocampus.

The hippocampus is a highly stress susceptible structure and hippocampal abnormalities have been reported in a host of psychiatric disorders including major depression and post-traumatic stress disorder (PTSD). The hippocampus appears to be particularly susceptible to early life stress with a graded reduction in volume based on number of types (multiplicity) or severity of maltreatment. We assessed whether the most important predictors of adult hippocampal volume were multiplicity, severity or duration of exposure or timing of maltreatment during developmental sensitive periods. 3T MRIs were collected on 336 unmedicated, right-handed subjects (132M/204F, 18-25 years). Exposure to broad categories of abuse and neglect during each year of childhood were assessed using the Maltreatment and Abuse Chronology of Exposure scale and evaluated using artificial intelligence and predictive analytics. Male hippocampal volume was predicted by neglect, but not abuse, up through 7 years of age. Female hippocampal volume was predicted by abuse, but not neglect, at 10, 11, 15 and 16 years. Exposure at peak age had greater predictive importance than multiplicity, severity or duration. There were also marked gender differences in subfields and portions (head, body or tail) affected by exposure. History and symptoms of major depression, PTSD or anxiety disorders were not predictive of hippocampal volume once maltreatment was accounted for. Neglect appears to foster inadequate hippocampal development in males while abuse appears to produce a stress-related deficit in females. Studies assessing hippocampal volume in psychiatric disorders need to control for the gender-specific effects of abuse and neglect.

Childhood maltreatment is associated with alteration in global network fiber-tract architecture independent of history of depression and anxiety.

Childhood maltreatment is a major risk factor for psychopathology. It is also associated with alterations in the network architecture of the brain, which we hypothesized may play a significant role in the development of psychopathology. In this study, we analyzed the global network architecture of physically healthy unmedicated 18-25 year old subjects (n=262) using diffusion tensor imaging (DTI) MRI and tractography. Anatomical networks were constructed from fiber streams interconnecting 90 cortical or subcortical regions for subjects with no-to-low (n=122) versus moderate-to-high (n=140) exposure to maltreatment. Graph theory analysis revealed lower degree, strength, global efficiency, and maximum Laplacian spectra, higher pathlength, small-worldness and Laplacian skewness, and less deviation from artificial networks in subjects with moderate-to-high exposure to maltreatment. On balance, local clustering was similar in both groups, but the different clusters were more strongly interconnected in the no-to-low exposure group. History of major depression, anxiety and attention deficit hyperactivity disorder did not have a significant impact on global network measures over and above the effect of maltreatment. Maltreatment is an important factor that needs to be taken into account in studies examining the relationship between network differences and psychopathology.

Does sleep disruption mediate the effects of childhood maltreatment on brain structure?

Background: Childhood maltreatment is associated with alterations in morphology of stress susceptible brain regions. Maltreatment is also known to markedly increase risk for psychopathology and to have an enduring disruptive effect on sleep. Objective: To determine whether abnormalities in sleep continuity have effects on brain morphometry and to evaluate the extent to which sleep impairments mediate the effects of maltreatment on brain structure. Method: Maltreatment and Abuse Chronology of Exposure (MACE) scale ratings, actigraph-assessed sleep and 3T MRI were obtained on N = 37 18-19-year-old participants recruited from the community (N = 34 with neuroimaging). Results: Fourteen participants had no history of maltreatment while N = 23 were exposed, on average, to 4.7 types of maltreatment. Multiplicity of maltreatment was strongly associated with reduced sleep efficiency, increased wake after sleep onset time and number/duration of awakenings, which were independent of effects of maltreatment on depression and anxiety. The most important predictors of impaired sleep were exposure to parental non-verbal emotional abuse at 9-10 years of age. Reduced sleep efficiency correlated with reduced grey matter volume in hippocampus including CA1 subfield, molecular layer and dentate gyrus as well as inferior frontal gyrus and insula. Sleep mediated 39-46% of the effects of maltreatment on volume of hippocampal structures and inferior frontal gyrus. Conclusions: Actigraph-assessed sleep is disrupted in maltreated late teens and mediates a significant portion of the effects of maltreatment on hippocampal volume. Studies are needed to assess whether efforts to enhance sleep in maltreated children can pre-empt or ameliorate neurobiological consequences of maltreatment.

Objetivo: determinar si las anomalías en la continuidad del sueño tienen efectos sobre la morfometría cerebral y evaluar en qué medida las alteraciones del sueño intervienen en los efectos del maltrato sobre la estructura del cerebro. Método: Se obtuvieron las puntuaciones de la Escala de cronología de la exposición al maltrato y al abuso (MACE, por sus siglas en inglés), sueño evaluado por actigraph y 3T MRI en N = 37 participantes de 18-19 años reclutados en la comunidad (N = 34 con neuroimagen). Resultados: Catorce participantes no tenían antecedentes de malos tratos mientras que N = 23 habían estado expuestos, de media, a 4.7 tipos de maltrato. La multiplicidad de los malos tratos se asoció fuertemente con una menor eficiencia del sueño, tiempo mayor de vigilia después de la hora de inicio del sueño y el número / duración de despertares, que fueron independientes de los efectos del maltrato sobre la depresión y la ansiedad. Los predictores más importantes de problemas de sueño fueron la exposición al abuso emocional no verbal de los padres a los 9-10 años de edad. La reducción de la eficiencia del sueño se correlacionó con la reducción del volumen de la materia gris en el hipocampo, incluido el subcampo CA1, la capa molecular y la circunvolución dentada, así como la circunvolución frontal inferior y la ínsula. El sueño mediaba en el 39-46% de los efectos del maltrato sobre el volumen de las estructuras del hipocampo y la circunvolución frontal inferior. Conclusiones: el sueño evaluado por Actigraph se ve alterado en adolescentes mayores maltratados y media en una parte importante de los efectos del maltrato sobre el volumen del hipocampo. Se necesitan estudios para evaluar si los esfuerzos para mejorar el sueño en los niños maltratados pueden adelantar o mejorar las consecuencias neurobiológicas del maltrato.

The effects of childhood maltreatment on brain structure, function and connectivity.

Maltreatment-related childhood adversity is the leading preventable risk factor for mental illness and substance abuse. Although the association between maltreatment and psychopathology is compelling, there is a pressing need to understand how maltreatment increases the risk of psychiatric disorders. Emerging evidence suggests that maltreatment alters trajectories of brain development to affect sensory systems, network architecture and circuits involved in threat detection, emotional regulation and reward anticipation. This Review explores whether these alterations reflect toxic effects of early-life stress or potentially adaptive modifications, the relationship between psychopathology and brain changes, and the distinction between resilience, susceptibility and compensation.

Oceanic Distribution, Behaviour, and a Winter Aggregation Area of Adult Atlantic Sturgeon, Acipenser oxyrinchus oxyrinchus, in the Bay of Fundy, Canada.

Seasonal distribution of adult Atlantic sturgeon was examined using pop-up satellite archival tags (PSATs) and ultrasonic transmitters deployed in the Saint John River, New Brunswick, Canada. Seven MK10 PSATs programmed for release in June 2012 and seven MiniPAT PSATs programmed for release in February and April 2013 were deployed in August 2011 and 2012, respectively. Eleven of 14 PSATs surfaced and transmitted depth and temperature data archived for the duration of their deployment (121-302 days). Among these eleven PSATs, five were recovered and 15-sec archival data was downloaded. Following exit from the Saint John River in the fall, tagged fish occupied a mean monthly depth of 76.3-81.6 m at temperatures as low as 4.9˚C throughout the winter before returning to shallower areas in the spring. The majority of ultrasonic detections occurred in the Bay of Fundy, but fish were detected as far as Riviere Saint-Jean, Quebec, approximately 1500 km from the Bay of Fundy (representing long-distance migratory rates of up to 44 km/day). All PSATs were first detected in the Bay of Fundy. Tags that released in February and April were found 5-21 km offshore of the Saint John Harbour, while tags that released in June were first detected in near shore areas throughout the Bay of Fundy. The substrate at winter tag release locations (estimated from backward numerical particle-tracking experiments) consisted primarily of moraines and postglacial mud substrate with low backscatter strength, indicative of soft or smooth seabed. Based on the proximity of winter tag release locations, the consistent depths observed between fish, and previous research, it is suspected that a winter aggregation exists in the Bay of Fundy. This study expands the understanding of the marine distribution and range of Atlantic sturgeon on the east coast of Canada.

Actigraph measures discriminate pediatric bipolar disorder from attention-deficit/hyperactivity disorder and typically developing controls.

BACKGROUND: Distinguishing pediatric bipolar disorder (BD) from attention-deficit hyperactivity disorder (ADHD) can be challenging. Hyperactivity is a core feature of both disorders, but severely disturbed sleep and circadian dysregulation are more characteristic of BD, at least in adults. We tested the hypothesis that objective measures of activity, sleep, and circadian rhythms would help differentiate pediatric subjects with BD from ADHD and typically developing controls. METHODS: Unmedicated youths (N = 155, 97 males, age 5-18) were diagnosed using DSM-IV criteria with Kiddie-SADS PL/E. BD youths (n = 48) were compared to typically developing controls (n = 42) and children with ADHD (n = 44) or ADHD plus comorbid depressive disorders (n = 21). Three-to-five days of minute-to-minute belt-worn actigraph data (Ambulatory Monitoring Inc.), collected during the school week, were processed to yield 28 metrics per subject, and assessed for group differences with analysis of covariance. Cross-validated machine learning algorithms were used to determine the predictive accuracy of a four-parameter model, with measures reflecting sleep, hyperactivity, and circadian dysregulation, plus Indic's bipolar vulnerability index (VI). RESULTS: There were prominent group differences in several activity measures, notably mean 5 lowest hours of activity, skewness of diurnal activity, relative circadian amplitude, and VI. A predictive support vector machine model discriminated bipolar from non-bipolar with mean accuracy of 83.1 ± 5.4%, ROC area of 0.781 ± 0.071, kappa of 0.587 ± 0.136, specificity of 91.7 ± 5.3%, and sensitivity of 64.4 ± 13.6%. CONCLUSIONS: Objective measures of sleep, circadian rhythmicity, and hyperactivity were abnormal in BD. Wearable sensor technology may provide bio-behavioral markers that can help differentiate children with BD from ADHD and healthy controls.

Impacts of Interannual Ocean Circulation Variability on Japanese Eel Larval Migration in the Western North Pacific Ocean.

The Japanese eel larvae hatch near the West Mariana Ridge seamount chain and travel through the North Equatorial Current (NEC), the Kuroshio, and the Subtropical Countercurrent (STCC) region during their shoreward migration toward East Asia. The interannual variability of circulation over the subtropical and tropical regions of the western North Pacific Ocean is affected by the Philippines-Taiwan Oscillation (PTO). This study examines the effect of the PTO on the Japanese eel larval migration routes using a three-dimensional (3D) particle tracking method, including vertical and horizontal swimming behavior. The 3D circulation and hydrography used for particle tracking are from the ocean circulation reanalysis produced by the Japan Coastal Ocean Predictability Experiment 2 (JCOPE2). Our results demonstrate that bifurcation of the NEC and the strength and spatial variation of the Kuroshio affect the distribution and migration of eel larvae. During the positive phase of PTO, more virtual eels ("v-eels") can enter the Kuroshio to reach the south coast of Japan and more v-eels reach the South China Sea through the Luzon Strait; the stronger and more offshore swing of the Kuroshio in the East China Sea leads to fewer eels entering the East China Sea and the onshore movement of the Kuroshio to the south of Japan brings the eels closer to the Japanese coast. Significant differences in eel migration routes and distributions regulated by ocean circulation in different PTO phases can also affect the otolith increment. The estimated otolith increment suggests that eel age tends to be underestimated after six months of simulation due to the cooler lower layer temperature. Underestimation is more significant in the positive PTO years due to the wide distribution in higher latitudes than in the negative PTO years.

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.

Locomotor micro-activities associated with therapeutic responses in patients with seasonal affective disorders.

BACKGROUND: Psychomotor retardation, leaden paralysis and fatigue are often used to describe patients with depressive disorders. However, there is limited understanding of their meaning and how they are objectively manifested in the physical world. Patients with seasonal affective disorder (SAD) are characteristically hypoactive, and experience restoration in energy during effective treatment with bright light. In this study, we attempt to identify quantitative metrics of psychomotor activity that correspond to the clinical perceptions of hypoactivity and to the early activating effects of treatment. METHODS: Novel means of assessing the microstructure of activity was employed using wavelets and Hurst exponents to indicate the proclivity of subjects to persist at higher and lower levels of activity. This was assesed using actigraphs in 16 unmedicated patients with SAD before and following two weeks of bright light therapy. RESULTS: Two weeks of phototherapy had no significant effect on mean levels of diurnal activity, but altered the microstructure of the activity. Specifically, phototherapy produced a significant reduction in inertial resistance in patients who had a 50% or greater reduction in Hamilton Depression scores (n=8), as reflected in reduced tendency to persist at low levels of activity. There was also a strong correlation between ratings of fatigue and measures of persistence at high versus low activity in initial responders, but not in initial non-responders. CONCLUSION: These findings suggest that light therapy alters the nature of diurnal activity troughs in early responsive patients, reducing their tendency to persist at low levels, possibly reflecting an alleviation of psychomotor retardation.