The effect of NK3-Saporin injection within the arcuate nucleus on puberty, the LH surge, and the response to Senktide in female sheep†.

The timing of puberty onset is reliant on increased gonadotropin-releasing hormone (GnRH). This elicits a corresponding increase in luteinizing hormone (LH) due to a lessening of sensitivity to the inhibitory actions of estradiol (E2). The mechanisms underlying the increase in GnRH release likely involve a subset of neurons within the arcuate (ARC) nucleus of the hypothalamus that contain kisspeptin, neurokinin B (NKB), and dynorphin (KNDy neurons). We aimed to determine if KNDy neurons in female sheep are critical for: timely puberty onset; the LH surge; and the response to an intravenous injection of the neurokinin-3 receptor (NK3R) agonist, senktide. Prepubertal ewes received injections aimed at the ARC containing blank-saporin (control, n = 5) or NK3-saporin (NK3-SAP, n = 6) to ablate neurons expressing NK3R. Blood samples taken 3/week for 65 days following surgery were assessed for progesterone to determine onset of puberty. Control ewes exhibited onset of puberty at 33.2 ± 3.9 days post sampling initiation, whereas 5/6 NK3-SAP treated ewes didn't display an increase in progesterone. After an artificial LH surge protocol, surge amplitude was lower in NK3-SAP ewes. Finally, ewes were treated with senktide to determine if an LH response was elicited. LH pulses were evident in both groups in the absence of injections, but the response to senktide vs saline was similar between groups. These results show that KNDy cells are necessary for timely puberty onset and for full expresson of the LH surge. The occurrence of LH pulses in NK3-SAP treated ewes may indicate a recovery from an apulsatile state.

Neuronal Firing and Waveform Alterations through Ictal Recruitment in Humans.

Analyzing neuronal activity during human seizures is pivotal to understanding mechanisms of seizure onset and propagation. These analyses, however, invariably using extracellular recordings, are greatly hindered by various phenomena that are well established in animal studies: changes in local ionic concentration, changes in ionic conductance, and intense, hypersynchronous firing. The first two alter the action potential waveform, whereas the third increases the "noise"; all three factors confound attempts to detect and classify single neurons. To address these analytical difficulties, we developed a novel template-matching-based spike sorting method, which enabled identification of 1239 single neurons in 27 patients (13 female) with intractable focal epilepsy, that were tracked throughout multiple seizures. These new analyses showed continued neuronal firing with widespread intense activation and stereotyped action potential alterations in tissue that was invaded by the seizure: neurons displayed increased waveform duration (p < 0.001) and reduced amplitude (p < 0.001), consistent with prior animal studies. By contrast, neurons in "penumbral" regions (those receiving intense local synaptic drive from the seizure but without neuronal evidence of local seizure invasion) showed stable waveforms. All neurons returned to their preictal waveforms after seizure termination. We conclude that the distinction between "core" territories invaded by the seizure versus "penumbral" territories is evident at the level of single neurons. Furthermore, the increased waveform duration and decreased waveform amplitude are neuron-intrinsic hallmarks of seizure invasion that impede traditional spike sorting and could be used as defining characteristics of local recruitment.SIGNIFICANCE STATEMENT Animal studies consistently show marked changes in action potential waveform during epileptic discharges, but acquiring similar evidence in humans has proven difficult. Assessing neuronal involvement in ictal events is pivotal to understanding seizure dynamics and in defining clinical localization of epileptic pathology. Using a novel method to track neuronal firing, we analyzed microelectrode array recordings of spontaneously occurring human seizures, and here report two dichotomous activity patterns. In cortex that is recruited to the seizure, neuronal firing rates increase and waveforms become longer in duration and shorter in amplitude as the neurons are recruited to the seizure, while penumbral tissue shows stable action potentials, in keeping with the "dual territory" model of seizure dynamics.

Ventromedial Prefrontal Volume in Adolescence Predicts Hyperactive/Inattentive Symptoms in Adulthood.

Youths with attention-deficit/hyperactivity disorder symptomatology often exhibit residual inattention and/or hyperactivity in adulthood; however, this is not true for all individuals. We recently reported that dimensional, multi-informant ratings of hyperactive/inattentive symptoms are associated with ventromedial prefrontal cortex (vmPFC) structure. Herein, we investigate the degree to which vmPFC structure during adolescence predicts hyperactive/inattentive symptomatology at 5-year follow-up. Structural equation modeling was used to test the extent to which adolescent vmPFC volume predicts hyperactive/inattentive symptomatology 5 years later in early adulthood. 1104 participants (M = 14.52 years, standard deviation = 0.42; 583 females) possessed hyperactive/inattentive symptom data at 5-year follow-up, as well as quality controlled neuroimaging data and complete psychometric data at baseline. Self-reports of hyperactive/inattentive symptomatology were obtained during adolescence and at 5-year follow-up using the Strengths and Difficulties Questionnaire (SDQ). At baseline and 5-year follow-up, a hyperactive/inattentive latent variable was derived from items on the SDQ. Baseline vmPFC volume predicted adult hyperactive/inattentive symptomatology (standardized coefficient = -0.274, P < 0.001) while controlling for baseline hyperactive/inattentive symptomatology. These results are the first to reveal relations between adolescent brain structure and adult hyperactive/inattentive symptomatology, and suggest that early structural development of the vmPFC may be consequential for the subsequent expression of hyperactive/inattentive symptoms.

Heavy drinking in adolescents is associated with change in brainstem microstructure and reward sensitivity.

Heavy drinker adolescents: altered brainstem microstructure.

The cortical-cerebellar circuit is vulnerable to heavy drinking (HD) in adults. We hypothesized early microstructural modifications of the pons/midbrain region, containing core structures of the reward system, in HD adolescents. Thirty-two otherwise symptom-free HDs at age 14 (HD14) and 24 abstainers becoming HDs at age 16 (HD16) were identified in the community with the Alcohol Use Disorders Identification Test (AUDIT) and compared with abstainers. The monetary incentive delay (MID) task assessed reward-sensitive performance. Voxelwise statistics of diffusion tensor imaging (DTI) values in the thalamo-ponto-mesencephalic region were obtained using tract-based spatial statistics. Projections between the ventral tegmental area (VTA) and the nucleus accumbens (NAcc) were identified by probabilistic tractography. Lower fraction of anisotropy and higher radial diffusivity (RD) values were detected in the upper dorsal pons of HD14 adolescents, and a trend for higher RD in HD16, compared with abstainers. When expecting reward, HD14 had higher MID task success scores than abstainers, and success scores were higher with a lower number of tracts in all adolescents. In symptom-free community adolescents, a region of lower white matter (WM) integrity in the pons at age 14 was associated with current HD and predicted HD at age 16. HD was related to reward sensitivity.

Cross-scale effects of neural interactions during human neocortical seizure activity.

Small-scale neuronal networks may impose widespread effects on large network dynamics. To unravel this relationship, we analyzed eight multiscale recordings of spontaneous seizures from four patients with epilepsy. During seizures, multiunit spike activity organizes into a submillimeter-sized wavefront, and this activity correlates significantly with low-frequency rhythms from electrocorticographic recordings across a 10-cm-sized neocortical network. Notably, this correlation effect is specific to the ictal wavefront and is absent interictally or from action potential activity outside the wavefront territory. To examine the multiscale interactions, we created a model using a multiscale, nonlinear system and found evidence for a dual role for feedforward inhibition in seizures: while inhibition at the wavefront fails, allowing seizure propagation, feedforward inhibition of the surrounding centimeter-scale networks is activated via long-range excitatory connections. Bifurcation analysis revealed that distinct dynamical pathways for seizure termination depend on the surrounding inhibition strength. Using our model, we found that the mesoscopic, local wavefront acts as the forcing term of the ictal process, while the macroscopic, centimeter-sized network modulates the oscillatory seizure activity.

Role of paroxysmal depolarization in focal seizure activity.

We analyze the role of inhibition in sustaining focal epileptic seizure activity. We review ongoing seizure activity at the mesoscopic scale that can be observed with microelectrode arrays as well as at the macroscale of standard clinical EEG. We provide clinical, experimental, and modeling data to support the hypothesis that paroxysmal depolarization (PD) is a critical component of the ictal machinery. We present dual-patch recordings in cortical cultures showing reduced synaptic transmission associated with presynaptic occurrence of PD, and we find that the PD threshold is cell size related. We further find evidence that optically evoked PD activity in parvalbumin neurons can promote propagation of neuronal excitation in neocortical networks in vitro. Spike sorting results from microelectrode array measurements around ictal wave propagation in human focal seizures demonstrate a strong increase in putative inhibitory firing with an approaching excitatory wave, followed by a sudden reduction of firing at passage. At the macroscopic level, we summarize evidence that this excitatory ictal wave activity is strongly correlated with oscillatory activity across a centimeter-sized cortical network. We summarize Wilson-Cowan-type modeling showing how inhibitory function is crucial for this behavior. Our findings motivated us to develop a network motif of neurons in silico, governed by a reduced version of the Hodgkin-Huxley formalism, to show how feedforward, feedback, PD, and local failure of inhibition contribute to observed dynamics across network scales. The presented multidisciplinary evidence suggests that the PD not only is a cellular marker or epiphenomenon but actively contributes to seizure activity.NEW & NOTEWORTHY We present mechanisms of ongoing focal seizures across meso- and macroscales of microelectrode array and standard clinical recordings, respectively. We find modeling, experimental, and clinical evidence for a dual role of inhibition across these scales: local failure of inhibition allows propagation of a mesoscopic ictal wave, whereas inhibition elsewhere remains intact and sustains macroscopic oscillatory activity. We present evidence for paroxysmal depolarization as a mechanism behind this dual role of inhibition in shaping ictal activity.

Are children with unrecognised psychiatric disorders being excluded from school? A secondary analysis of the British Child and Adolescent Mental Health Surveys 2004 and 2007.

BACKGROUND: There is limited research that explores the association between exclusion from school and mental health, but it seems intuitively plausible that the recognition of mental difficulties by key teachers and parents would influence the likelihood of exclusion from school. METHODS: A secondary analysis of the British Child and Adolescent Mental Health survey 2004, (n = 7997) and the 2007 follow-up (n = 5326) was conducted. Recognition of difficulty was assessed via a derived variable that combined the first item of the Impact supplement of the Strengths and Difficulties Questionnaire which asked parents and teachers if they thought that the child has difficulties with emotions, behaviour and concentration, and the presence/absence of psychiatric disorder measured by the Development and Well-being Assessment. RESULTS: Adjusted logistic regression models demonstrated that children with recognised difficulties were more likely to be excluded [adjusted odds ratio (OR) 5.78, confidence interval 3.45-9.64, p < 0.001], but children with unrecognised difficulties [adjusted OR 3.58 (1.46-8.81) p < 0.005] or recognised subclinical difficulties [adjusted OR 3.42 (2.04-5.73) p < 0.001] were also more likely to be excluded than children with no difficulties. Children with conduct disorder and attention deficit hyperactivity disorder were most likely to be excluded compared with other types of disorder. CONCLUSION: Exclusion from school may result from a failure to provide timely and effective support rather than a failure to recognise psychopathology.

Western organizational change capacity theory and its application to public health organizations in China: A multiple case analysis.

As health reform becomes a crucial task for both Chinese and United States government, public health organizations are required to adopt changes based on reform policy. Organizational Change Capacity theory is a Western theory that indicates the capacities that organizations should possess when pursuing successful organizational change. This study seeks to understand the applicability of this theory to Chinese public health organizations by contrasting organizations that have achieved success or remained challenged in implementing organizational change to optimize health reform. The research questions are: Is the Organizational Change Capacity theory applicable in Chinese public health organizations? How should it be modified to best fit Chinese public health organizations? Seventy-two participants from 12 public health organizations in Beijing and Xi'an were recruited for interviews and follow-up questionnaires that asked for experiences during their organizational changes. During the analysis, a new Chinese Organizational Change Capacity theory with nine main themes emerged. This new framework provides a guideline for Chinese public health organizations to evaluate their change capacity, and offers a theoretical foundation for researchers to design interventions that increase these organizations' capacity in achieving successful change.

Regulation of GnRH pulsatility in ewes.

Early work in ewes provided a wealth of information on the physiological regulation of pulsatile gonadotropin-releasing hormone (GnRH) secretion by internal and external inputs. Identification of the neural systems involved, however, was limited by the lack of information on neural mechanisms underlying generation of GnRH pulses. Over the last decade, considerable evidence supported the hypothesis that a group of neurons in the arcuate nucleus that contain kisspeptin, neurokinin B and dynorphin (KNDy neurons) are responsible for synchronizing secretion of GnRH during each pulse in ewes. In this review, we describe our current understanding of the neural systems mediating the actions of ovarian steroids and three external inputs on GnRH pulsatility in light of the hypothesis that KNDy neurons play a key role in GnRH pulse generation. In breeding season adults, estradiol (E2) and progesterone decrease GnRH pulse amplitude and frequency, respectively, by actions on KNDy neurons, with E2 decreasing kisspeptin and progesterone increasing dynorphin release onto GnRH neurons. In pre-pubertal lambs, E2 inhibits GnRH pulse frequency by decreasing kisspeptin and increasing dynorphin release, actions that wane as the lamb matures to allow increased pulsatile GnRH secretion at puberty. Less is known about mediators of undernutrition and stress, although some evidence implicates kisspeptin and dynorphin, respectively, in the inhibition of GnRH pulse frequency by these factors. During the anoestrus, inhibitory photoperiod acting via melatonin activates A15 dopaminergic neurons that innervate KNDy neurons; E2 increases dopamine release from these neurons to inhibit KNDy neurons and suppress the frequency of kisspeptin and GnRH release.

Neuroanatomical Relationship of Neuronal Nitric Oxide Synthase to Gonadotropin-Releasing Hormone and Kisspeptin Neurons in Adult Female Sheep and Primates.

BACKGROUND: Neuronal intermediates that communicate estrogen and progesterone feedback to gonadotropin-releasing hormone (GnRH) neurons are essential for modulating reproductive cyclicity. Individually, kisspeptin and nitric oxide (NO) influence GnRH secretion. However, it is possible these 2 neuronal intermediates interact with one another to affect reproductive cyclicity. METHODS: We investigated the neuroanatomical relationship of one isoform of the enzyme that synthesizes NO, neuronal NO synthase (nNOS), to kisspeptin and GnRH in adult female rhesus monkeys and sheep using dual-label immunofluorescence. Additionally, we evaluated if the phase of the reproductive cycle would affect these relationships. RESULTS: Overall, no effect of the stage of cycle was observed for any variable in this study. In the arcuate nucleus (ARC) of sheep, 98.8 ± 3.5% of kisspeptin neurons colocalized with nNOS, and kisspeptin close-contacts were observed onto nNOS neurons. In contrast to ewes, no colocalization was observed between kisspeptin and nNOS in the infundibular ARC of primates, but kisspeptin fibers were apposed to nNOS neurons. In the preoptic area of ewes, 15.0 ± 4.2% of GnRH neurons colocalized with nNOS. In primates, 38.8 ± 10.1% of GnRH neurons in the mediobasal hypothalamus colocalized with nNOS, and GnRH close-contacts were observed onto nNOS neurons in both sheep and primates. CONCLUSION: Although species differences were observed, this work establishes a neuroanatomical framework between nNOS and kisspeptin and nNOS and GnRH in adult female nonhuman primates and sheep.

Comparing the characteristics and outcomes of parent- and teacher-reported oppositional defiant disorder: findings from a national sample.

BACKGROUND: Parents and teachers often disagree on the presence of Oppositional Defiant Disorder (ODD) in children. It has been argued that ODD should be treated as an informant-specific disorder. This study compared the characteristics of children identified with ODD by parent- and teacher report. METHODS: We used the 1999 British Child and Adolescent Mental Health Survey, including more than 10,000 observations aged 5-15 years, to investigate symptom profiles, risk factors, comorbidities and three-year outcomes of parent- and teacher-reported ODD. RESULTS: Parents and teachers poorly agreed on ODD diagnosis. Parent-reported ODD was more strongly associated with a concurrent anxiety disorder at time1 and a successive diagnosis of ODD at time2 . Beyond these differences, parent- and teacher- reported ODD showed similar symptom profiles, risk factors, comorbidities, and outcomes. CONCLUSIONS: Children identified by parent report and teacher report share more similarities than differences in the characteristics of their disorder. This does not support the formation of informant-specific ODD disorders.

Epidemiological study of child and adolescent psychiatric disorders in Lithuania.

BACKGROUND: From the public health perspective, epidemiological data of child mental health and psychosocial correlates were necessary and very lacking in Lithuanian society that has been undergoing rapid socio-economic change since the past decades. Together with determining the prevalence rates of disorders and assessing the needs for the services, this study has also shifted attention from the highly selective samples of children attending children and adolescent mental health services towards less severe cases of psychopathology as well as different attitudes of parents and teachers. The aim of the first epidemiological study in Lithuania was to identify the prevalence of psychiatric disorders in the community sample of children. METHODS: Child psychiatric disorders were investigated in a representative sample of 3309 children aged 7-16 years (1162 7-10-year-olds and 2147 11-16-year-olds), using a two-phase design with the Lithuanian version of the Strengths and Difficulties Questionnaire (SDQ) in the first screening phase, and the Development and Well-Being Assessment (DAWBA) in the second diagnostic phase. RESULTS: The estimated point prevalence of ICD-10 psychiatric disorders was 13.1% for the total sample (14.0% for the child sample and 12.1% for adolescent sample). The most common groups of disorders were Conduct disorders 6.6% (7.1% for child sample and 6.0% for adolescent sample), Anxiety disorders 5.0% (5.9% for child sample and 6.0% for adolescent sample), with Hyperkinesis being less common 2.0% (2.7% for child sample and 1.2% for adolescent sample). Potential risk factors were related to individual characteristics of the child (gender, poor general health, and stressful life experiences), and the family (single parenthood, foster care, unfavourable family climate, disciplining difficulties, worries related to TV or computer use). CONCLUSIONS: The overall prevalence of youth psychiatric disorders was relatively high in this representative Lithuanian sample compared to Western European countries. The SDQ and DAWBA measures appear useful for the further research and clinical practice in this society.

Should Clinicians Split or Lump Psychiatric Symptoms? The Structure of Psychopathology in Two Large Pediatric Clinical Samples from England and Norway.

It has been suggested that the structure of psychiatric phenomena can be reduced to a few symptom dimensions. These proposals, mainly based on epidemiological samples, may not apply to clinical populations. We tested the structure of psychiatric symptoms across two pediatric clinical samples from England (N = 8434) and Norway (N = 5866). Confirmatory factor analyses of the parent-reported Strengths and Difficulties Questionnaire (SDQ) evaluated the relative fit of several models, including a first-order model, a second-order model with the widely-established broad symptom dimensions of internalizing-externalizing, and two bi-factor models capturing a general psychopathology factor. Predictive value of the SDQ subscales for psychiatric disorders was examined. A first-order five-factor solution better fit the data. The expected SDQ subscale(s) related best to the corresponding psychiatric diagnosis. In pediatric clinical samples, a granular approach to psychiatric symptoms where several dimensions are considered seems to fit the data better than models based on lumping symptoms into internalizing/externalizing dimensions.

Innovations in Practice: Body dysmorphic disorder in youth - using the Development and Well-Being Assessment as a tool to improve detection in routine clinical practice.

BACKGROUND: Body Dysmorphic Disorder (BDD) is a distressing disorder that is widely underdetected in youth. This study aimed to examine the potential utility of the Development and Well-Being Assessment (DAWBA) as a tool to improve recognition of BDD in routine clinical practice. METHODS: One hundred and sixty-one patients assessed across two national and specialist child and adolescent mental health services, one specialising in mood disorders and one specialising in obsessive compulsive disorder and BDD, were included in this study. Results from the DAWBA were compared with clinical diagnosis to examine the utility of the DAWBA in detecting BDD. RESULTS: Only 27% of participants who received a diagnosis of BDD at assessment had been referred with concerns about appearance anxiety suggesting significant under detection in youth mental health services. Using the single-screener question on the DAWBA, it was possible to correctly identify 97% of cases with BDD. CONCLUSIONS: Body dysmorphic disorder often goes undetected in routine clinical practice. The DAWBA shows promise as a tool for helping clinicians to accurately detect BDD in routine clinical practice.

Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy.

OBJECTIVE: Evaluate the seizure-reduction response and safety of mesial temporal lobe (MTL) brain-responsive stimulation in adults with medically intractable partial-onset seizures of mesial temporal lobe origin. METHODS: Subjects with mesial temporal lobe epilepsy (MTLE) were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. RESULTS: There were 111 subjects with MTLE; 72% of subjects had bilateral MTL onsets and 28% had unilateral onsets. Subjects had one to four leads placed; only two leads could be connected to the device. Seventy-six subjects had depth leads only, 29 had both depth and strip leads, and 6 had only strip leads. The mean follow-up was 6.1 ± (standard deviation) 2.2 years. The median percent seizure reduction was 70% (last observation carried forward). Twenty-nine percent of subjects experienced at least one seizure-free period of 6 months or longer, and 15% experienced at least one seizure-free period of 1 year or longer. There was no difference in seizure reduction in subjects with and without mesial temporal sclerosis (MTS), bilateral MTL onsets, prior resection, prior intracranial monitoring, and prior vagus nerve stimulation. In addition, seizure reduction was not dependent on the location of depth leads relative to the hippocampus. The most frequent serious device-related adverse event was soft tissue implant-site infection (overall rate, including events categorized as device-related, uncertain, or not device-related: 0.03 per implant year, which is not greater than with other neurostimulation devices). SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including patients with unilateral or bilateral MTLE who are not candidates for temporal lobectomy or who have failed a prior MTL resection.

Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.

OBJECTIVE: Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin. METHODS: Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset. RESULTS: There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6 months or longer and 14% experienced at least one seizure-free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices. SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.

Effective Mental Health Screening in Adolescents: Should We Collect Data from Youth, Parents or Both?

Youth- and parent-rated screening measures derived from the Strengths and Difficulties Questionnaire (SDQ) and Development and Well-Being Assessment (DAWBA) were compared on their psychometric properties as predictors of caseness in adolescence (mean age 14). Successful screening was judged firstly against the likelihood of having an ICD-10 psychiatric diagnosis and secondly by the ability to discriminate between community (N = 252) and clinical (N = 86) samples (sample status). Both, SDQ and DAWBA measures adequately predicted the presence of an ICD-10 disorder as well as sample status. The hypothesis that there was an informant gradient was confirmed: youth self-reports were less discriminating than parent reports, whereas combined parent and youth reports were more discriminating-a finding replicated across a diversity of measures. When practical constraints only permit screening for caseness using either a parent or an adolescent informant, parents are the better source of information.

Neural mechanisms controlling seasonal reproduction: principles derived from the sheep model and its comparison with hamsters.

Seasonal reproduction is a common adaptive strategy among mammals that allows for breeding to occur at times of the year when it is most advantageous for the subsequent survival and growth of offspring. A major mechanism responsible for seasonal reproduction is a striking increase in the responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the negative feedback effects of estradiol. The neural and neuroendocrine circuitry responsible for mammalian seasonal reproduction has been primarily studied in three animal models: the sheep, and two species of hamsters. In this review, we first describe the afferent signals, neural circuitry and transmitters/peptides responsible for seasonal reproductive transitions in sheep, and then compare these mechanisms with those derived from studies in hamsters. The results suggest common principles as well as differences in the role of specific brain nuclei and neuropeptides, including that of kisspeptin cells of the hypothalamic arcuate nucleus, in regulating seasonal reproduction among mammals.

Single unit action potentials in humans and the effect of seizure activity.

Spike-sorting algorithms have been used to identify the firing patterns of isolated neurons ('single units') from implanted electrode recordings in patients undergoing assessment for epilepsy surgery, but we do not know their potential for providing helpful clinical information. It is important therefore to characterize both the stability of these recordings and also their context. A critical consideration is where the units are located with respect to the focus of the pathology. Recent analyses of neuronal spiking activity, recorded over extended spatial areas using microelectrode arrays, have demonstrated the importance of considering seizure activity in terms of two distinct spatial territories: the ictal core and penumbral territories. The pathological information in these two areas, however, is likely to be very different. We investigated, therefore, whether units could be followed reliably over prolonged periods of times in these two areas, including during seizure epochs. We isolated unit recordings from several hundred neurons from four patients undergoing video-telemetry monitoring for surgical evaluation of focal neocortical epilepsies. Unit stability could last in excess of 40 h, and across multiple seizures. A key finding was that in the penumbra, spike stereotypy was maintained even during the seizure. There was a net tendency towards increased penumbral firing during the seizure, although only a minority of units (10-20%) showed significant changes over the baseline period, and notably, these also included neurons showing significant reductions in firing. In contrast, within the ictal core territories, regions characterized by intense hypersynchronous multi-unit firing, our spike sorting algorithms failed as the units were incorporated into the seizure activity. No spike sorting was possible from that moment until the end of the seizure, but recovery of the spike shape was rapid following seizure termination: some units reappeared within tens of seconds of the end of the seizure, and over 80% reappeared within 3 min (τrecov = 104 ± 22 s). The recovery of the mean firing rate was close to pre-ictal levels also within this time frame, suggesting that the more protracted post-ictal state cannot be explained by persistent cellular neurophysiological dysfunction in either the penumbral or the core territories. These studies lay the foundation for future investigations of how these recordings may inform clinical practice.See Kimchi and Cash (doi:10.1093/awv264) for a scientific commentary on this article.

Trait Mindfulness Predicts Efficient Top-Down Attention to and Discrimination of Facial Expressions.

In social situations, skillful regulation of emotion and behavior depends on efficiently discerning others' emotions. Identifying factors that promote timely and accurate discernment of facial expressions can therefore advance understanding of social emotion regulation and behavior. The present research examined whether trait mindfulness predicts neural and behavioral markers of early top-down attention to, and efficient discrimination of, socioemotional stimuli. Attention-based event-related potentials (ERPs) and behavioral responses were recorded while participants (N = 62; White; 67% female; Mage = 19.09 years, SD = 2.14 years) completed an emotional go/no-go task involving happy, neutral, and fearful facial expressions. Mindfulness predicted larger (more negative) N100 and N200 ERP amplitudes to both go and no-go stimuli. Mindfulness also predicted faster response time that was not attributable to a speed-accuracy trade-off. Significant relations held after accounting for attentional control or social anxiety. This study adds neurophysiological support for foundational accounts that mindfulness entails moment-to-moment attention with lower tendencies toward habitual patterns of responding. Mindfulness may enhance the quality of social behavior in socioemotional contexts by promoting efficient top-down attention to and discrimination of others' emotions, alongside greater monitoring and inhibition of automatic response tendencies.