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Objective: To characterize the extent of CNS involvement in children with Pompe disease using brain MRI and developmental assessments., Methods: The study included 14 children (ages 6-18 years) with infantile Pompe disease (IPD) (n = 12) or late-onset Pompe disease (LOPD) (n = 2) receiving enzyme replacement therapy. White matter (WM) hyperintense foci seen in the brain MRIs were systematically quantified using the Fazekas scale (FS) grading system with a novel approach: the individual FS scores from 10 anatomical areas were summed to yield a total FS score (range absent [0] to severe [30]) for each child. The FS scores were compared to developmental assessments of cognition and language obtained during the same time period., Results: Mild to severe WM hyperintense foci were seen in 10/12 children with IPD (median age 10.6 years) with total FS scores ranging from 2 to 23. Periventricular, subcortical, and deep WM were involved. WM hyperintense foci were seen throughout the path of the corticospinal tracts in the brain in children with IPD. Two children with IPD had no WM hyperintense foci. Children with IPD had relative weaknesses in processing speed, fluid reasoning, visual perception, and receptive vocabulary. The 2 children with LOPD had no WM hyperintense foci, and high scores on most developmental assessments., Conclusion: This study systematically characterized WM hyperintense foci in children with IPD, which could serve as a benchmark for longitudinal follow-up of WM abnormalities in patients with Pompe disease and other known neurodegenerative disorders or leukodystrophies in children., (© 2020 American Academy of Neurology.)

Purpose: Enzyme replacement therapy (ERT) with recombinant human acid-α glucosidase (rhGAA) at standard dose of 20 mg/kg every other week is insufficient to halt the long-term progression of myopathy in Pompe disease., Methods: We conducted a retrospective study on infantile-onset Pompe disease (IPD) and late-onset Pompe disease (LOPD) patients with onset before age 5 years, ≥12 months of treatment with standard dose ERT, and rhGAA immunogenic tolerance prior to dose escalation. Long-term follow-up of up to 18 years was obtained. We obtained physical therapy, lingual strength, biochemical, and pulmonary assessments as dose was escalated., Results: Eleven patients with IPD (n = 7) or LOPD (n = 4) were treated with higher doses of up to 40 mg/kg weekly. There were improvements in gross motor function measure in 9/10 patients, in lingual strength in 6/6 patients, and in pulmonary function in 4/11. Significant reductions in urinary glucose tetrasaccharide, creatine kinase, aspartate aminotransferase, and alanine aminotransferase were observed at 40 mg/kg weekly compared with lower doses (p < 0.05). No safety or immunogenicity concerns were observed at higher doses., Conclusion: Higher rhGAA doses are safe, improve gross motor outcomes, lingual strength, pulmonary function measures, and biochemical markers in early-onset Pompe disease, and should be considered in patients with clinical and functional decline.

The electrical equivalent circuit for a neuron is composed of common electrical components in a configuration that replicates the passive electrical properties and behaviors of the neural membrane. It is a powerful tool used to derive such fundamental neurophysiological equations as the Hodgkin-Huxley equations, and it is also the basis for well-known exercises that help students to model the passive (Ohmic) properties of the neuronal membrane. Unfortunately, as these exercises require basic knowledge of electronics, they are generally not physically conducted in biomedical courses, but remain merely conceptual exercises in a book or simulations on a computer. In such manifestations, they lack the "hands-on" appeal for students and teachers afforded by laboratory experimentations. Here, we propose a new approach to these experiments in which a desktop 3D printer and conductive paint are used to build the circuit and the popular programmable microcontroller, the Arduino UNO, is used as a graphical oscilloscope when connected to a standard computer. This set-up has the advantage of being very easy to build and less clumsy than a circuit in a prototyping board or connected with alligator clips, with the added benefit of being conveniently portable for classroom demonstrations. Most importantly, this method allows the monitoring of real-time changes in the current flowing through the circuit by means of a graphical display (by way of the Arduino) at a fraction of the cost of commercially available oscilloscopes., (Copyright © 2019 Faculty for Undergraduate Neuroscience.)

Aim: It is now necessary to investigate whether recovery in psychosis is possible without the use of antipsychotic medication. This study will determine (1) whether a first-episode psychosis (FEP) group receiving intensive psychosocial interventions alone can achieve symptomatic remission and functional recovery; (2) whether prolonging the duration of untreated psychosis (DUP) in a sub-group according to randomisation will be associated with a poorer outcome and thereby establish whether the relationship between DUP and outcome is causative; and (3) whether neurobiological changes observed in FEP are associated with the psychotic disorder or antipsychotic medication. Baseline characteristics of participants will be presented., Methods: This study is a triple-blind randomized placebo-controlled non-inferiority trial. The primary outcome is the level of functioning measured by the Social and Occupational Functioning Assessment Scale at 6 months. This study is being conducted at the Early Psychosis Prevention and Intervention Centre, Melbourne and includes young people aged 15 to 24 years with a DSM-IV psychotic disorder, a DUP less than 6 months and not high risk for suicide or harm to others. Strict discontinuation criteria are being applied. Participants are also undergoing three 3-Tesla-MRI scans., Results: Ninety participants have been recruited and baseline characteristics are presented., Conclusions: Staged treatment and acceptability guidelines in early psychosis will determine whether antipsychotic medications are indicated in all young people with a FEP and whether antipsychotic medication can be safely delayed. Furthermore, the relative contribution of psychotic illness and antipsychotic medication in terms of structural brain changes will also be elucidated. The findings will inform clinical practice guidelines., (© 2018 John Wiley & Sons Australia, Ltd.)

Relaxation oscillators are nonlinear electronic circuits that produce a repetitive non-sinusoidal waveform when sufficient voltage is applied. In this fashion, they are reminiscent of integrate-and-fire neuron models, except that they also include components with hysteresis, and thus require no threshold rule to determine when an impulse has occurred or to return the voltage to its reset value. Here, I discuss the pros and cons of teaching elementary neurophysiology using first-order linear integrate-and-fire neurons versus relaxation oscillator circuits. I suggest that the shortcomings of both types of models are useful in order to foster a critical understanding of the neurophysiology underlying the firing dynamics of biological neurons.

Family members caring for a young person diagnosed with the onset of mental health problems face heightened stress, depression, and social isolation. Despite evidence for the effectiveness of family based interventions, sustaining access to specialist family interventions is a major challenge. The availability of the Internet provides possibilities to expand and sustain access to evidence-based psychoeducation and personal support for family members. In this paper we describe the therapeutic model and the components of our purpose-built moderated online social therapy (MOST) program for families. We outline the background to its development, beginning with our face-to-face EPISODE II family intervention, which informed our selection of therapeutic content, and the integration of recent developments in positive psychology. Our online interventions for carers integrate online therapy, online social networking, peer and expert support, and online social problem solving which has been designed to reduce stress in carers. The initial version of our application entitled Meridian was shown to be safe, acceptable, and feasible in a feasibility study of carers of youth diagnosed with depression and anxiety. There was a significant reduction in self-reported levels of stress in caregivers and change in stress was significantly correlated with use of the system. We have subsequently launched a cluster RCT for caregivers with a relative diagnosed with first-episode psychosis. Our intervention has the potential to improve access to effective specialist support for families facing the onset of serious mental health problems in their young relative.

Incarcerated women enter the prison setting with remarkable histories of trauma, mental health and substance abuse issues. Given the stress of incarceration and separation from their children, families, and significant others, it is not surprising that many women experience increased anxiety, depression, and problems with sleep. Due to these negative outcomes, it is imperative to find efficient non-pharmacological interventions. This pilot study examined the impact of a 12-week mindfulness based program on the stress, anxiety, depression and sleep of women with a total of 33 completing the study. In one group, women's perceived stress, anxiety and depression were all significantly lower following the intervention compared to prior to the intervention. Challenges with implementing the pilot study are addressed. Despite challenges and limitations, the low-cost non-pharmacological intervention has potential for a reducing the symptoms of anxiety and depression.

Carers' expressed emotion (EE) and patients' cannabis misuse are two of the most robust predictors of psychotic relapse. We aimed to examine the temporal relationship between EE and cannabis misuse. Sixty-three key carers of young people with first-episode psychosis (FEP) were assessed at baseline and 7-month follow-up. EE was measured in carers using the Family Questionnaire (FQ) and cannabis misuse in patients using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). Correlational and hierarchical logistic regression analyses were conducted to examine the temporal relationship between EE components (i.e. criticism and emotional over involvement) and cannabis misuse. Carers' criticism at baseline significantly predicted cannabis misuse according to the ASSIST at 7-month follow-up. The association remained significant after controlling for baseline symptom severity and social functioning (B=0.15, P=.02). Conversely, baseline cannabis misuse was not associated with carers' criticism at 7-month follow-up. Patients in families with high criticism showed a tendency to increase cannabis misuse over time whereas the opposite trend was observed in those with carers with low criticism. A family environment characterized by high criticism may become a key risk factor for worsening cannabis misuse over time in young people with FEP. Further studies should investigate the potential mechanisms (e.g., patient's anxiety or perceived stress) through which criticism increases cannabis misuse in FEP., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background: The effect of eating speed at a meal on appetite gut hormone responses and future food consumption is not clear. This study examined the effect of eating speed at breakfast on postprandial gut hormone responses, subjective appetite, and daily food consumption., Methods: Twenty-five participants [68% men; age, 25.9 (8.1) years; body mass index, 25.0 (3.2) kg/m] were recruited. Each participant consumed the same breakfast at a slow (30 minutes) and fast (10 minutes) speed, on 2 separate days, in a randomized crossover design. Blood samples were collected in the fasting state and 3 hours postprandially during each eating condition. Appetite was assessed over the same period using visual analog scales. Blood concentrations of orexigenic hormone, ghrelin, and anorexigenic hormones, glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), were determined. Daily food intake was measured, by food recall, after the slow and fast breakfast., Results: Mixed-model repeated-measures analysis showed no eating condition or eating condition by time interaction effect on ghrelin, GLP-1, PYY, hunger, or fullness. Significant eating speed by time interaction effect on desire to eat was found (P=0.007). Desire to eat was lower at 60 minutes (P=0.007) after breakfast began during the slow versus fast eating condition. Eating speed at breakfast did not affect daily energy and macronutrient intake., Conclusions: Eating speed at breakfast did not affect postprandial ghrelin, GLP-1, PYY, hunger, and fullness values or daily energy and macronutrient intake. Desire to eat was lower at 60 minutes in the slow versus fast eating condition, but this result could not be explained by the changes in meal-related hormones measured in the study.

Caring for young people with first-episode psychosis (FEP) is challenging and can adversely affect carer well-being, with limited evidence-based support materials available. We aimed to examine whether completion of a self-directed problem-solving bibliotherapy among carers of young people with FEP led to a better experience of caring, less distress and expressed emotion, and better general health than carers who only received treatment as usual (TAU). A randomized controlled trial was conducted across two early-intervention psychosis services in Melbourne, Australia. A total of 124 carers were randomized to problem-solving bibliotherapy intervention (PSBI) or TAU and assessed at baseline, 6-week and 16-week follow-up. Intent-to-treat analyses were carried out and indicated that recipients of PSBI had a more favorable experience of caring than those receiving TAU, and these effects were sustained at both follow-up time points. Across the other measures, both groups demonstrated improvements by week 16, although the PBSI group tended to improve earlier. The PSBI group experienced a greater reduction in negative emotional evaluations of the need to provide additional support to young people with FEP than the TAU group by week 6, while the level of psychological distress decreased at a greater rate from baseline to 6 weeks in the PSBI compared with the TAU group. These findings support the use of problem-solving bibliotherapy for first-time carers, particularly as a cost-effective adjunct to TAU.

Background: Carers of young people with first episode psychosis (FEP) often face burden. Understanding ways in which carers cope is not only important for providing support to them but might maximise patient outcomes. The aim of this study was to examine strategies carers use to cope with the burden of caring for a young person with FEP., Methods: The study was part of a randomized controlled trial focusing on the effectiveness of a problem-solving bibliotherapy intervention for carers of FEP patients, in terms of promoting coping and reducing psychological distress. Baseline data on the Ways of Coping (WOC) scale was available for 124 carers aged between 18 and 66 years. Principal component analysis with PROMAX rotation was used to determine the number of factors that could be used to characterise coping behaviour. Regression analyses were used to determine how the factors were related to carers' demographics, burden, psychological well-being and expressed emotion., Results: Approximately half of the carers reported that they frequently use positive coping techniques such as self-talk, active problem solving, and positive reframing. The factor analysis yielded five factors: (i) cognitive-escape coping; (ii) optimistic coping; (iii) seeking connections; (iv) tension reduction; and (v) distancing. The relationships between these factors and demographic characteristics, carers' perception of burden, expressed emotion, and psychological distress are reported., Conclusions: Avoidance coping strategies are related to psychological distress, emotional over-involvement, and increased carer burden. Interventions facilitating the use of adaptive problem solving and positive re-appraisal will promote carer coping and reduce psychological distress., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The effectiveness of a novel 7-month psychosocial treatment designed to prevent the second episode of psychosis was evaluated in a randomized controlled trial at 2 specialist first-episode psychosis (FEP) programs. An individual and family cognitive behavior therapy for relapse prevention was compared with specialist FEP care. Forty-one FEP patients were randomized to the relapse prevention therapy (RPT) and 40 to specialist FEP care. Participants were assessed on an array of measures at baseline, 7- (end of therapy), 12-, 18-, 24-, and 30-month follow-up. At 12-month follow-up, the relapse rate was significantly lower in the therapy condition compared with specialized treatment alone (P = .039), and time to relapse was significantly delayed for those in the relapse therapy condition (P = .038); however, such differences were not maintained. Unexpectedly, psychosocial functioning deteriorated over time in the experimental but not in the control group; these differences were no longer statistically significant when between-group differences in medication adherence were included in the model. Further research is required to ascertain if the initial treatment effect of the RPT can be sustained. Further research is needed to investigate if medication adherence contributes to negative outcomes in functioning in FEP patients who have reached remission, or, alternatively, if a component of RPT is detrimental.

In recent years, early intervention services have attempted to identify people with a first episode of psychosis as early as possible, reducing the duration of untreated psychosis and changing the timing of delivery of interventions. The logic of early intervention is based partly on accessing people in a more treatment responsive stage of illness in which psychosocial damage is less extensive, and partly on remediating a putatively active process of neuroprogression that leads to pathophysiological, symptomatic and structural changes, hence improving symptomatic and functional outcomes. However, as in other areas of health care, earlier identification of new patients may mean that different treatment approaches are indicated. The corollary of early detection is that the sequence and complexion of treatment strategies for first episode psychosis has been revaluated. Examples include the minimal effective dosage of antipsychotic medication and the content of psychosocial interventions. With the substantial reductions of DUP now seen in many early psychosis services, based on clinical staging and stepped care principles, it is even possible that the immediate introduction of antipsychotic medication may not be necessary for all first episode psychosis cases, but that potentially safer interventions, which may be more acceptable to many patients, such as comprehensive psychosocial intervention, may constitute effective treatment at least for a subgroup of patients. In this paper, we review this theoretical background and describe a randomised controlled trial currently underway at the Early Psychosis Prevention and Intervention Centre (EPPIC) in Melbourne designed to test outcomes for first episode psychosis patients in response to two different treatments: intensive psychosocial intervention plus antipsychotic medication versus intensive psychosocial intervention plus placebo. This is a theoretically and pragmatically novel study in that it will provide evidence as to whether intensive psychosocial intervention alone is sufficient for a subgroup of first episode psychosis patients in a specialised early intervention service, and provide a test of the heuristic clinical staging model. By experimentally manipulating duration of untreated psychosis, the study will also provide a methodologically strong test of the effect of delaying the introduction of antipsychotic medication, as well as helping to disentangle the effects of antipsychotic medications and the putative neurobiological processes associated with brain changes and symptom profiles in the early phase of psychotic disorders. The study has been carefully crafted to satisfy critical ethical demands in this challenging research domain., (Crown Copyright (c) 2010. Published by Elsevier B.V. All rights reserved.)

Objective: We have previously reported that our combined individual and family cognitive-behavioral therapy (CBT) relapse prevention therapy (RPT) was effective in reducing relapse rates compared to treatment as usual (TAU) within a specialist program for young, first-episode psychosis patients who had reached remission on positive symptoms. Here, we report the outcomes for family participants of DSM-IV-diagnosed first-episode psychosis patients recruited between November 2003 and May 2005 over a 2.5-year follow-up period. The primary hypothesis was that, compared to family members receiving TAU, family participants who received RPT would have significantly improved appraisals of stressors related to caregiving. Secondary hypotheses were that RPT would be associated with reduced expressed emotion and improved psychological distress., Method: Family members were assessed at baseline and at 7-month, 12-month, 18-month, 24-month, and 30-month follow-up on appraisal of caregiving, expressed emotion, and psychological distress using the Experience of Caregiving Inventory, The Family Questionnaire, and the General Health Questionnaire of 28 Items, respectively. The family component of RPT was based on family behavioral therapy for schizophrenia with a specific focus on psychoeducation and CBT for relapse prevention., Results: Thirty-two families received RPT, and 31 families received TAU. There were significant group effects for aspects of the appraisal of caregiving, including negative symptoms, positive personal experiences, and total positive score on the Experience of Caregiving Inventory. Time effects were evident for emotional overinvolvement and for aspects of the appraisal of caregiving. There were no significant effects for psychological distress., Conclusions: The relatives of patients who received RPT perceived less stress related to their relative's negative symptoms and an increase in perceived opportunities to make a positive contribution to the care of their relative compared to carers in the TAU condition. Cognitive-behavioral therapy for relapse prevention showed promise in improving the experience of caregiving for family members of first-episode psychosis patients over a 2.5-year follow-up period., Trial Registration: anzctr.org.au Identifier: ACTRN12605000514606., (Copyright 2010 Physicians Postgraduate Press, Inc.)

Background: Little research has focused on delineating the specific predictors of emotional over-involvement (EOI) and critical comments (CC) in the early course of psychosis. The purpose of this study was to investigate the differential relationships of EOI and CC with relevant predictors in relatives of first-episode psychosis (FEP) patients., Method: Baseline patient-related factors including psychotic symptoms, depression and duration of untreated psychosis (DUP) and carer attributes comprising CC, EOI, burden of care and carers' stress and depression were assessed in a cohort of 63 remitted FEP patients and their relatives. Carers were reassessed at 7 months follow-up., Results: Baseline analysis showed that EOI was more strongly correlated with family stress compared with CC, whereas CC yielded a stronger association with DUP than EOI. Carers' CC at follow-up was not significantly predicted by either baseline family stress, burden of care or patient-related variables. Conversely, baseline EOI predicted both family stress and burden of care at 7 months follow-up. Finally, family burden of care at follow-up was a function of baseline EOI and patients' depressive symptoms., Conclusions: This study provides preliminary support to the postulate that EOI and CC may be influenced by separate factors early in the course of psychosis and warrant future research and therapeutic interventions as separate constructs. Implications for family interventions in the early phase of psychosis and the prevention of CC and EOI are discussed.

Objective: To investigate predictors of adherence with a cognitive-behavioural intervention in first-episode psychosis (FEP) patients., Method: Predictors of adherence to cognitive-behavioural therapy (CBT) were longitudinally investigated in the experimental arm of a randomized controlled trial designed to evaluate the effectiveness of a CBT intervention for relapse prevention early in the course of psychosis when compared with treatment as usual within 2 high quality, youth oriented, specialist FEP programs (the EPISODE II trial)., Results: Longer duration of untreated psychosis (DUP) and poorer level of insight predicted poor adherence to CBT. This association remained significant after controlling for potential confounders., Conclusions: Treatment delay may decrease adherence with CBT in FEP patients. Reducing DUP and promoting insight early in the course of psychosis are likely to enhance adherence with CBT.

Objective: Patients with first-episode psychosis are responsive to acute-phase treatments, but relapse rates are high. This study aimed to evaluate the effectiveness of a psychosocial treatment designed to prevent the second episode of psychosis compared with standardized early psychosis care., Method: In a randomized controlled trial, conducted at the Early Psychosis Prevention and Intervention Centre and Barwon Health, Australia, a multimodal individual and family cognitive-behavioral therapy for relapse prevention was compared with standardized case management within a specialist early psychosis service. Patients aged 15 to 25 years with a first episode of a DSM-IV psychotic disorder were recruited between November 2003 and May 2005. The main outcome measures were the number of relapses and time to first relapse., Results: Forty-one first-episode psychosis patients were randomly assigned to the relapse prevention therapy (RPT) and 40 to standardized case management. At the 7-month follow up, the relapse rate was significantly lower in the therapy condition compared to treatment as usual (p = .042) and time to relapse was significantly longer for the RPT condition (p = .03). The number needed to treat was 6 over 7 months., Conclusions: Interim findings suggest that RPT provided within a specialist early psychosis program was effective in reducing relapse in early psychosis when compared with standardized early psychosis case management., Trial Registration: www.anzctr.org.au Identifier: ACTRN12605000514606., (©Copyright 2009 Physicians Postgraduate Press, Inc.)

Objectives: Establishing treatment fidelity is one of the most important aspects of psychotherapy research. Treatment fidelity refers to the methodological strategies used to examine and enhance the reliability and validity of psychotherapy. This study sought to develop and evaluate a measure specifically designed to assess fidelity to the different therapeutic components (i.e. therapy phases) of the individual intervention of a psychotherapy clinical trial (the EPISODE II trial)., Method: A representative sample of sessions stratified by therapy phase was assessed using a specifically developed fidelity measure (Relapse Prevention Therapy-Fidelity Scale, RPT-FS). Each RPT-FS subscale was designed to include a different component/phase of therapy and its major therapeutic ingredients., Results: The measure was found to be reliable and had good internal consistency. The RPT-FS discriminated, almost perfectly, between therapy phases. The analysis of the therapeutic strategies implemented during the intervention indicated that treatment fidelity was good throughout therapy phases. While therapists primarily engaged in interventions from the appropriate therapeutic phase, flexibility in therapy was evident., Conclusions: This study described the development of a brief, reliable and internally consistent measure to determine both treatment fidelity and the therapy components implemented throughout the intervention. This methodology can be potentially useful to determine those components related to therapeutic change.

Focally treating the head brain of the medicinal leech Hirudo medicinalis with various biogenic amines affected the initiation, termination and maintenance of fictive swimming (i.e., the neural correlate of swimming). Application of serotonin to saline surrounding only the head brain inhibited fictive swimming, whereas removing serotonin induced swimming. This contrasts sharply with previous observations that serotonin applied to the nerve cord induces swimming. Although application of octopamine to the brain activated swimming, a mixture of octopamine and serotonin inhibited swimming. Subsequent removal of this mixture from the brain activated robust swimming and was more potent for activating swimming than either the removal of serotonin or the application of octopamine. Swim episodes induced by brain-specific manipulations of octopamine had more swim bursts per episode than those induced by serotonin. These brain-specific effects of the amines on fictive swimming are probably due to the modulation of higher-order circuits that control locomotion in the leech. We observed that serotonin or a mixture of serotonin and octopamine hyperpolarized an identified descending brain interneuron known as Tr2. Removal of the mixture caused Tr2 to exhibit membrane potential depolarizations that correlated in time with the expression of swim episodes.

It is well established that neural networks respond to a wide variety of modulatory substances by which they can become reconfigured, yet few studies have examined the effects of neurotransmitter mixtures on such networks. In a previous study of the medicinal leech using triple intracellular recordings, we found that stimulation of identified mechanosensory neurons activated both the serotonergic cell 21 (a swimgating neuron) and the dorsal lateral octopamine (DLO) cell. Because these findings suggested that serotonin (5-HT) and octopamine (OA) may be released together, we investigated the effects of 5-HT and OA mixtures on isolated nerve cords of Hirudo medicinalis (which contained both head and tail brains). Fifty micromolar OA, 50 microM 5-HT, or a mixture of 50 microM OA and 50 microM 5-HT was bath applied to the nerve cord under constant perfusion conditions. Additional experiments were performed with combinations of either 25 or 100 microM OA and 5-HT. Neural activity was examined specifically in the segmentally repeated dorsal posterior (DP) nerve because it has been shown to contain identified swim motor units. Nonadditive effects of amine combinations were most apparent in their ability to decrease overall activity in the DP nerve and to alter patterned motor activity in the form of fictive swimming. Whereas swim burst activity has been previously shown to increase in nerve cords bathed in either 5-HT or OA solutions alone, we demonstrated that a mixture of the two amines resulted in a robust decrease in the number of swim bursts expressed and an inhibition of swim activity in preparations already swimming. Most compelling was the observation that when the amine mixture was replaced with normal saline, swim burst activity increased dramatically. We discuss that the effects of amine mixtures may be due to their interaction with descending interneurons known to trigger and inhibit swimming as the mixture-induced effects were not observed in nerve cords lacking the head and tail brains. Because the net effect of the two amines was not simply additive (i.e., 5-HT or OA is known to activate swimming, yet the mix inhibits swimming), this result reveals yet another layer of complexity inherent in "simpler" invertebrate nervous systems.