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Anxiety‐related diseases are more than twice as common in women than in men, and in women, symptoms may be exacerbated during the late luteal phase of the menstrual cycle. Despite this, most research into the underlying mechanisms, which drives drug development, have been carried out using male animals. In an effort to redress this imbalance, we compared responses of male and female Wistar rats during exposure to two unconditioned threatening stimuli that evoke panic‐related defensive behaviours: confrontation with a predator (Bothrops alternatus) and acute exposure to hypoxia (7% O2). Threatened by venomous snake, male and female rats initially displayed defensive attention, risk assessment, and cautious interaction with the snake, progressing to defensive immobility to overt escape. Both males and females displayed higher levels of risk assessment but less interaction with the predator. They also spent more time in the burrow, displaying inhibitory avoidance, and more time engaged in defensive attention, and non‐oriented escape behaviour. In females, anxiety‐like behaviour was most pronounced in the oestrous and proestrus phases whereas panic‐like behaviour was more pronounced during the dioestrus phase, particularly during late dioestrus. Acute hypoxia evoked panic‐like behaviour (undirected jumping) in both sexes, but in females, responsiveness in late dioestrus was significantly greater than at other stages of the cycle. The results reveal that females respond in a qualitatively similar manner to males during exposure to naturally occurring threatening stimuli, but the responses of females is oestrous cycle dependent with a significant exacerbation of panic‐like behaviour in the late dioestrus phase. [ABSTRACT FROM AUTHOR]

Aims: Botulinum toxin A (BTX‐A) is a well‐established treatment for refractory idiopathic overactive bladder (OAB). It has also been used with short‐term success in treating idiopathic urinary retention. However, efficacy and complication rates are variable and predicting those likely to benefit most from treatment would enable personalization of therapy and optimization of outcomes. At the International Consultation on Incontinence‐Research Society (ICI‐RS) meeting in 2019 a Think Tank addressed the question of how we can improve the way we phenotype patients undergoing BTX‐A treatment. Methods: The Think Tank conducted a literature review and expert consensus meeting focussing on how advances in basic science research of the mechanism of action of BTX‐A, as well as assessment of psychological comorbidity, can be translated into clinical practice to improve patient selection for therapy. Results: Idiopathic OAB and idiopathic urinary retention are heterogenous conditions encompassing several phenotypes with multiple potential pathophysiological mechanisms. Animal models have demonstrated a central nervous system mechanism of action of intravesically injected BTX‐A and this has been confirmed in human functional MRI studies, but whether this tool can be used to predict outcome from treatment remains to be determined. Phenotyping based on psychological comorbidity using validated screening tools should be studied as a way to potentially optimize patient selection for therapy. Conclusions: Advances in basic science research into the mechanism of action of BTX‐A have improved our understanding of the pathophysiology of OAB and may lead to novel ways to phenotype patients. Psychological assessment is another way in which phenotyping may be improved. Areas for further research are proposed. [ABSTRACT FROM AUTHOR]

Aims: Sacral nerve stimulation (SNS) is widely used to treat refractory idiopathic overactive bladder (OAB) and idiopathic urinary retention. However, clinical outcomes are variable and understanding predictive factors for success or side‐effects would enable personalization of therapy and optimization of outcomes. At the International Consultation on Incontinence‐Research Society meeting 2019, a Think Tank was convened to discuss how advances in the basic science study of SNS may be translatable into clinical practice to improve outcomes of patients undergoing SNS treatment. Methods: We conducted a literature review and expert consensus meeting focusing on current methods of phenotyping patients and specifically, how advances in basic science research of the mechanism of action of SNS can be translated into clinical practice to improve patient selection for therapy. Results: The terms "Idiopathic OAB" and "idiopathic urinary retention" encompass several underlying pathophysiological phenotypes. Commonly, phenotyping is based on clinical and urodynamic factors. Animal studies have demonstrated that high‐frequency stimulation can produce rapid onset, reversible conduction block in peripheral nerves. Altering stimulation parameters may potentially enable personalization of therapy depending upon the clinical indication in the future. Similarly, advances in conditional and closed‐loop stimulation may offer greater efficacy for certain patients. Phenotyping based on psychological comorbidity requires further study to potentially optimize patient selection for therapy. Conclusions: Idiopathic OAB and idiopathic urinary retention are heterogenous conditions with multiple potential underlying phenotypes. Tailoring stimulation parameters to the needs of each individual according to phenotype could optimize outcomes. Assessing psychological comorbidity may improve patient selection. Areas for further research are proposed. [ABSTRACT FROM AUTHOR]

Objective: To determine electrical changes in the heart in a chronic, nonstatus model of epilepsy. Methods: Electrocorticography (ECoG) and electrocardiography (ECG) of nine animals (five made epileptic by intrahippocampal injection of tetanus neurotoxin (TeNT) and four controls), are monitored continuously by radiotelemetry for up to 7 weeks. Results: Epileptic animals develop a median of 168 seizures, with postictal tachycardias reaching a mean of 487 beats/min and lasting a mean of 661 seconds. Ictal changes in heart rate include tachycardia and in the case of convulsive seizures, bradyarrhythmias resembling Mobitz type 1 second‐degree atrioventricular block; notably the P‐R interval increased before block. Postictally, the amplitude of T wave increases. Interictally, QT dependence on RR is modest and conventional QT corrections prove ineffective. Interictal QT intervals, measured at a heart rate of 400 bpm, increased from 65 to 75 ms, an increase dependent on seizure incidence over the preceding 10‐14 days. Significance: Repeated seizures induce a sustained tachycardia and increase in QT interval of the ECG and evoke arrhythmias including periods of atrioventricular block during Racine type 4 and 5 seizures. These changes in cardiac function may predispose to development in fatal arrhythmias and sudden death in humans with epilepsy. [ABSTRACT FROM AUTHOR]

Objective: To investigate how prolonged seizure activity affects cardiorespiratory function and activity of pre‐Bötzinger complex, leading to sudden death. Methods: Urethane‐anesthetized female Long‐Evans rats were implanted with nasal thermocouple; venous and arterial cannulae; and electrodes for electrocardiography (ECG) and hippocampal, cortical, and brainstem recording. Kainic acid injection into the ventral hippocampus induced status epilepticus. Results: Seizures caused hypertension, tachycardia, and tachypnea punctuated by recurrent transient apneas. Salivation increased considerably: in 11 of 12 rats, liquid with alkaline pH consistent with saliva was expelled from the mouth. Most transient apneas were obstructive: nasal airflow ceased, while, in 83%, efforts to breathe persisted as continued rhythmic activity of respiratory pre‐Bötzinger neurons, inspiratory electromyography (EMG), and excursions of the chest wall and abdomen. Blood pressure oscillated in time with respiratory efforts. This pattern also occurred in a minority of cases (16%) of incomplete apnea, but not in rare cases (1%) of transient central apneas. During transient obstructive apneas, the frequency of all inspiratory efforts decreased abruptly by ~30%, suggesting a resetting of the central respiratory rhythm generator. Twenty‐two of thirty‐one rats died, due either to obstructive apnea (12) or central apnea following progressive slowing of respiration (10). Most rats dying of central apnea had experienced several transient obstructive apneas. Negative DC field potential shifts of the brainstem followed the final breath, consistent with previous reports on spreading depolarization in mouse models. Timing suggests that the DC shift is a consequence rather than cause of respiratory collapse. Cardiac activity continued for tens of seconds. Significance: Seizure activity in forebrain induces pronounced autonomic activation and disrupts activity in medullary respiratory centers, resulting in death from either obstructive or central apnea. These results directly inform mechanisms of death in status epilepticus, and indirectly provide clues to mechanisms of sudden unexpected death in epilepsy (SUDEP). [ABSTRACT FROM AUTHOR]

The prevalence of lower urinary tract (LUT) symptoms increases with age but the etiology is unknown. This article aims to identify research directions that clarify the basis of this association. The initial question is whether biological age is the variable of interest or a time-dependent accumulation of factors that impact on LUT function at rates that differ between individuals. In particular, the accumulation of conditions or agents due to inflammatory states or tissue ischemia is important. Much of the above has been concerned with changes to bladder function and morphology. However, the outflow tract function is also affected, in particular changes to the function of external sphincter skeletal muscle and associated sacral motor nerve control. Nocturia is a cardinal symptom of LUT dysfunction and is more prevalent with aging. Urine production is determined by diurnal changes to the production of certain hormones as well as arterial blood pressure and such diurnal rhythms are blunted in subjects with nocturia, but the causal links remain to be elucidated. Changes to the central nervous control of LUT function with age are also increasingly recognized, whether in mid-brain/brainstem regions that directly affect LUT function or in higher centers that determine psycho-social and emotional factors impinging on the LUT. In particular, the linkage between increasing white matter hyperintensities and LUT dysfunction during aging is recognized but not understood. Overall, a more rational approach is being developed to link LUT dysfunction with factors that accumulate with age, however, the precise causal pathways remain to be characterized. Neurourol. Urodynam. 36:854-858, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

New Findings What is the topic of this review? This article reviews data from studies on human participants and animal models showing how electrical stimulation in deep brain structures (deep brain stimulation) can influence autonomic function., What advances does it highlight? Focusing on the control of the cardiovascular system and bladder function, it highlights the potential for development of deep brain stimulation as a new treatment option for patients with autonomic dysfunction., Deep brain stimulation (DBS) in humans has come of age as a tool to treat movement disorders including Parkinson's disease tremor and dystonia as well as a panoply of other disease states including headache, epilepsy, obesity, eating disorders, depression, obsessive compulsive disorder, Tourette's syndrome, addiction and chronic pain. Increasingly, practitioners of DBS are reporting autonomic side effects, which intriguingly, sometimes result in improved autonomic function. Focussing on the effects of stimulation at periaqueductal and periventricular sites on cardiovascular function and control of micturition, this review shows that data obtained from studies in animals is now being confirmed in humans. Lowering of blood pressure and improved baroreflex function can be evoked in humans by DBS at these midbrain sites as well as increased bladder capacity. The findings highlight the tantalizing possibility that DBS could be developed for treatment of dysfunctional autonomic states in humans. [ABSTRACT FROM AUTHOR]

Most of the time the bladder is locked in storage mode, switching to voiding only when it is judged safe and/or socially appropriate to urinate. Here we show, in humans and rodents, that deep brain stimulation in the periaqueductal gray matter can rapidly and reversibly manipulate switching within the micturition control circuitry, to defer voiding and maintain urinary continence, even when the bladder is full. Manipulation of neural continence pathways by deep brain stimulation may offer new avenues for the treatment of urinary incontinence of central origin. Ann Neurol 2012;72:144-147 [ABSTRACT FROM AUTHOR]

In humans, adverse physical and/or psychological traumas in childhood may predispose to developing psychiatric disorders in adulthood, including panic disorder. To model early life adversity in mice, we subjected male and female C57BL/6 J mice to a limited bedding and nesting (LBN) protocol between postnatal days 2–9 and investigated its effect on responsiveness to panicogenic challenges in adulthood. Panic‐like escape behaviour was assessed during exposure to a high concentration of CO2 (20%) or in the beetle mania task (BMT), used to model respiratory and non‐respiratory‐related types of panic respectively. Neonatal exposure to LBN increased panic‐like jumping during the CO2 challenge in male but not female mice. In an initial pharmacological validation of the BMT as a panic‐inducing paradigm, undirected jumping and horizontal escape behaviours were reduced significantly by the panicolytic alprazolam (0.05 and 0.1mg.kg−1 i.p.) whilst tolerance to the close proximity of the aversive robo‐beetle increased. The anxiolytic diazepam (1 mg.kg−1 i.p.) reduced only the number of horizontal escape attempts. In both sexes, previous experience of LBN significantly enhanced the number of horizontal escape episodes, indicating a pro‐panic phenotype. Directed escape to access a safe ledge on the wall of the test arena, which was seen only in males, was also reduced significantly following LBN. These findings indicate that early life adversity produced by fragmented and unpredictable maternal care promotes a sex‐specific increase in susceptibility to panic‐like behaviour in adulthood. Whilst non‐respiratory‐related panic‐like behaviour was enhanced in both sexes, females were resilient to respiratory‐related challenges. [ABSTRACT FROM AUTHOR]

An introduction to this issue of "Experimental Physiology," focusing on brain-heart interactions in health and disease, is presented.