Children are being seen more readily by nurse practitioners when behavioral concerns arise. Atten... more Children are being seen more readily by nurse practitioners when behavioral concerns arise. Attentiondeficit/hyperactivity disorder (ADHD) is a common and costly behavioral condition seen by nurse practitioners. ADHD may also affect children's sensory processing. Symptoms of ADHD often include those of sensory processing dysfunction. Sensory processing disorder, a condition in which sensory processing dysfunction impacts everyday functioning, is a condition commonly seen with ADHD. For children with ADHD and associated conditions, it is important for nurse practitioners to be versed in conservative management of these conditions, including occupational therapy.
The effects of chronic administration of the antidepressant drugs desipramine, nortryptiline and ... more The effects of chronic administration of the antidepressant drugs desipramine, nortryptiline and paroxetine (PAR) (10 mg/kg/day, 21 days) on changes in turning (circling) behavior and on norepinephrine (NE), dopamine (DA) and serotonin and their metabolites 3,4-dihydroxyphenylacetic acid and 5-hydroxyindole acetic acid (5-HIAA) in the medial prefrontal cortex (PFC), nucleus aecumbens and striatum were evaluated in rats. All three drugs eliminated turning biases in right turning rats. All drugs increased DA concentrations in the PFC while PAR increased NE in the PFC and reduced 5-HIAA in all three structures. The results are discussed with reference to previous findings involving brain asymmetry in depression.
The development of selective corticotropin-releasing factor type-1 (CRF1) receptor antagonists re... more The development of selective corticotropin-releasing factor type-1 (CRF1) receptor antagonists represents a potential novel treatment for depression. These studies evaluated CRF1 receptor antagonists for antidepressant-like activity in mice. Subchronic dosing of both R 121919 (3-[6-(dimethylamino)-4-methyl-pyrid-3-yl]-2,5-dimethyl-N,N-dipropyl-pyrazolo[2,3-a]pyrimidin-7-amine) and DMP 696 (4-(1,3-dimethoxyprop-2-ylamino)-2,7-dimethyl-8-(2,4-dichlorophenyl)-pyrazolo[1,5-a]-1,3,5-triazine) significantly decreased immobility time in the tail suspension test (at 30 and at 3 and 10 mg/kg, i.p., respectively). These antidepressant-like effects were observed at doses that did not impair general locomotor activity. Neither antalarmin (N-butyl-N-ethyl-[2,5,6-trimethyl-7-(2,4,6)trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine) nor DMP 904 (4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine) had an effect indicative of antidepressant-like activity. These results suggest that the tail suspension assay may have utility to identify CRF1 receptor antagonists with antidepressant-like activity. Moreover, the results lend support to the theory that some nonpeptidic CRF1 receptor antagonists may possess antidepressant-like activity and therefore represent a promising novel pharmacotherapeutic strategy in the treatment of depression.
Background Medication and psychotherapy treatments for posttraumatic stress disorder (PTSD) provi... more Background Medication and psychotherapy treatments for posttraumatic stress disorder (PTSD) provide insufficient benefit for many patients. Substantial preclinical and clinical data indicate abnormalities in the hypothalamic-pituitary-adrenal axis, including signaling by corticotropin-releasing factor, in the pathophysiology of PTSD. Methods We conducted a double-blind, placebo-controlled, randomized, fixed-dose clinical trial evaluating the efficacy of GSK561679, a corticotropin-releasing factor receptor type 1 (CRF 1) antagonist in adult women with PTSD. The trial randomized 128 participants, of whom 96 completed the six-week treatment period. Results In both the intent-to-treat and completer samples, GSK561679 failed to show superiority over placebo on the primary outcome of change in Clinician Administered PTSD Scale total score. Adverse event frequencies did not significantly differ between GSK561679-and placebo-treated subjects. Exploration of the CRF 1 SNP rs110402 found response to GSK561679 and placebo did not significantly differ by genotype alone. However, subjects who had experienced a moderate or severe history of childhood abuse and who were also GG homozygotes for rs110402 showed significant improvement after treatment with GSK561679 (n=6) but not with placebo (n=7) on the PTSD Symptom Scale, Self-Report. Conclusions The results of this trial, the first evaluating a CRF 1 antagonist for the treatment of PTSD, combined with other negative trials of CRF 1 antagonists for major depressive disorder, generalized anxiety disorder, and
Children who are over-responsive to sensation have defensive and "fight or flight" reactions to o... more Children who are over-responsive to sensation have defensive and "fight or flight" reactions to ordinary levels of sensory stimulation in the environment. Based on clinical observations, sensory over-responsivity is hypothesized to reflect atypical neural integration of sensory input. To examine a possible underlying neural mechanism of the disorder, integration of simultaneous multisensory auditory and somatosensory stimulation was studied in twenty children with sensory over-responsivity (SOR) using event-related potentials (ERPs). Three types of sensory stimuli were presented and ERPs were recorded from thirty-two scalp electrodes while participants watched a silent cartoon: bilateral auditory clicks, right somatosensory median nerve electrical pulses, or both simultaneously. The paradigm was passive; no behavioral responses were required. To examine integration, responses to simultaneous multisensory auditory-somatosensory stimulation were compared to the sum of unisensory auditory plus unisensory somatosensory responses in four timewindows: (60-80 ms, 80-110 ms, 110-150 ms, and 180-220 ms). Specific midline and lateral electrode sites were examined over scalp regions where auditory-somatosensory integration was expected based on previous studies. Midline electrode sites (Fz, Cz, and Pz) showed significant integration during two time-windows: 60-80 ms and 180-220 ms. Significant integration was also found at contralateral electrode site (C3) for the timewindow between 180 and 220 ms. At ipsilateral electrode sites (C4 and CP6), no significant integration was found during any of the time-windows (i.e. the multisensory ERP was not significantly different from the summed unisensory ERP). These results demonstrate that MSI can be reliably measured in children with SOR and provide evidence that multisensory auditory-somatosensory input is integrated during both early and later stages of sensory information processing, mainly over fronto-central scalp regions.
Fragile X syndrome, a form of mental retardation caused by inadequate levels of fragile X mental ... more Fragile X syndrome, a form of mental retardation caused by inadequate levels of fragile X mental retardation protein (FMRP), is characterized by extreme sensitivity to sensory stimuli and increased behavioral and hormonal reactivity to stressors. Fmr1 knockout mice lack FMRP and exhibit abnormal responses to auditory stimuli. This study sought to determine whether Fmr1 knockout mice on an F1 hybrid background are normal in their response to footshock. Knockout mice were also examined for signs of hyperexcitation across an extended trial range, and serum corticosterone levels were evaluated in response to various stressors. The ability to acquire conditioned taste aversion was also assessed. Knockout mice exhibited no impairment in associative aversive learning or memory, since they successfully expressed conditioned taste aversion. Footshock-sensitivity, freezing behavior, and corticosterone response to various stressors did not differ between knockout and wild-type mice. However, knockout mice exhibited significantly increased responses during the extended test. The knockout mice's increased responsiveness to footshock in the extended test may be an indication of increased vulnerability to stress or enhanced emotional reactivity.
Foot-shock is used in a variety of behavioral tasks either as a motivational stimulus, a way to c... more Foot-shock is used in a variety of behavioral tasks either as a motivational stimulus, a way to characterize different rodents, or to test various pharmacological agents for their antinociceptive or analgesic effects. All these procedures need to assess foot-shock sensitivity either to rule out possible differences (when the shock is used as a motivational stimulus) or to use the differences to compare animals or treatments. In addition, many of the procedures that utilize foot-shock as a motivational stimulus evaluate freezing as an index of anxiety or fear. In the present study, data obtained by an automated computer system was compared with data obtained by human observers to validate the automated system for examining foot-shock sensitivity in mice. The different computer measures obtained for foot-shock sensitivity exhibited high correlations with human scoring at shock levels as low as 0.2 mA. The computer controlled analysis provided a non-subjective, quantifiable measurement of the foot-shock-induced response as well as freezing behavior. Automated data collection is an improvement over the methods of human visual observation in that the data collection is more standardized, efficient and consistent.
Sensory modulation disorder (SMD) is a severe inability to regulate responses to everyday sensory... more Sensory modulation disorder (SMD) is a severe inability to regulate responses to everyday sensory stimulation to which most people easily adapt. It is estimated to affect 5% to 16% of the general population of children. Although heterogeneity is seen in the presentation clinically, previous research has not empirically investigated whether the clinical heterogeneity of SMD can be classified into subtypes. This study explores a cohort of 98 children identified with SMD at the Department of Pediatric Rehabilitation by a member of the occupational therapy team at The Children's Hospital of Denver. Two subtypes of SMD were identified through cluster analysis based on data from 4 parent-report instruments. The first subtype is characterized by sensory seeking/craving, hyperactive, impulsive, externalizing (eg, delinquent, aggressive), unsocial, inadaptive, and impaired cognitive/social behavior. The second subtype is characterized by movement sensitivity, emotionally withdrawal, and low energy/weak behavior. Findings from this study present a step toward understanding and classifying the complexities of children with SMDs.
Spontaneous turning behavior and locomotor activity were evaluated for their ability to predict d... more Spontaneous turning behavior and locomotor activity were evaluated for their ability to predict differences in the voluntary consumption of ethanol in male Long-Evans rats. Animals were assessed for their preferred direction of turning behavior and for high vs. low levels of spontaneous locomotor activity, as determined during nocturnal testing in a rotometer. Subsequently, preference for a 10% ethanol solution vs. water was determined in a 24-h two-bottle home-cage free-choice paradigm. Rats exhibiting a right-turning preference consumed more ethanol than rats showing a left-turning preference. While locomotor activity alone did not predict differences in drinking, turning and locomotor activity together predicted differences in ethanol consumption. Low-activity right-turning rats consumed more ethanol than all the other groups of rats. Previous studies from this laboratory have shown that individual differences in turning behavior are accompanied by different asymmetries in dopamine (DA) function in the medial prefrontal cortex (mPFC). Individual differences in locomotor activity are associated with differences in nucleus accumbens (NAS) DA function. The present data suggest that variations in mPFC DA asymmetry and NAS DA function may underlie differences in the voluntary consumption of ethanol.
Ž. Ž. Ž. Ethanol 0.5 grkg i.p. 15 min prior to sacrifice increased homovanillic acid HVA levels i... more Ž. Ž. Ž. Ethanol 0.5 grkg i.p. 15 min prior to sacrifice increased homovanillic acid HVA levels in the left medial prefrontal cortex mPFC Ž. Ž. of left-turning rats and in the right mPFC of right-turning rats. In the nucleus accumbens NAS , ethanol decreased dopamine DA , Ž. 3,4-dihydroxyphenylacetic acid DOPAC , and HVA levels in rats that exhibited low levels of locomotor activity but not in rats that exhibited high levels of locomotor activity. This laboratory has previously shown that rats exhibiting differences in turning and locomotor activity behavior display different preferences for ethanol. The present results suggest that ethanol-induced differences in mPFC and NAS DA activity may be related to individual differences in the susceptibility to abuse ethanol.
Research in Developmental Disabilities, May 1, 2012
Attention deficit hyperactivity disorder (ADHD) is an early childhood developmental disorder that... more Attention deficit hyperactivity disorder (ADHD) is an early childhood developmental disorder that has received enormous attention in research. Typical characteristics of ADHD are developmentally inappropriate impulsivity, inattention, and hyperactivity (Barkley & Murphy, 1998; Kaplan, Sadock, & Grebb, 1994). ADHD is a costly and prevalent childhood disorder that affects 3-12% of school-aged children (
How can measuring children’s Electrodermal Activity (EDA) help improve the design of an occupatio... more How can measuring children’s Electrodermal Activity (EDA) help improve the design of an occupational therapy experience? Twenty-two children with sensory challenges such as Autism and ADHD participated in the study. Children attended occupational therapy as usual, while their physiological arousal (i.e., EDA) was measured with a wireless device on the bottom calf. Combining the EDA signal with video, researchers could better understand the emotional experience of therapy. All 22 children were able to wear the portable EDA sensors throughout the vigorous activities with minimal impact. Five insights generated from these observations are described in detail, with emphasis on how therapists used the findings to re-design their therapeutic process. This paper demonstrates how the ambulatory measurement of EDA can directly help with the emotional design of therapeutic services.
Fragile X syndrome, a form of mental retardation caused by inadequate levels of fragile X mental ... more Fragile X syndrome, a form of mental retardation caused by inadequate levels of fragile X mental retardation protein (FMRP), is characterized by extreme sensitivity to sensory stimuli and increased behavioral and hormonal reactivity to stressors. Fmr1 knockout mice lack FMRP and exhibit abnormal responses to auditory stimuli. This study sought to determine whether Fmr1 knockout mice on an F1 hybrid background are normal in their response to footshock. Knockout mice were also examined for signs of hyperexcitation across an extended trial range, and serum corticosterone levels were evaluated in response to various stressors. The ability to acquire conditioned taste aversion was also assessed. Knockout mice exhibited no impairment in associative aversive learning or memory, since they successfully expressed conditioned taste aversion. Footshock-sensitivity, freezing behavior, and corticosterone response to various stressors did not differ between knockout and wild-type mice. However, knockout mice exhibited significantly increased responses during the extended test. The knockout mice's increased responsiveness to footshock in the extended test may be an indication of increased vulnerability to stress or enhanced emotional reactivity.
Corticotropin-releasing factor (CRF) is a neuropeptide that plays a primary role in the neuroendo... more Corticotropin-releasing factor (CRF) is a neuropeptide that plays a primary role in the neuroendocrine, autonomic, and behavioral responses to stressors. Numerous reports suggest that alterations in CRF function contribute to the pathogenesis of depression. Recently, selective nonpeptide CRF type 1 (CRF 1) receptor antagonists have been discovered and several of these CRF 1 receptor antagonists have demonstrated antidepressantlike efficacy in animals. The CRF 1 receptor antagonists appear to be unique, as they exhibit antidepressant-like activity principally in animal models that are hyperresponsive to stress or under experimental conditions that alter endogenous stress-hormone activity. A nonpeptide CRF 1 receptor antagonist has also been shown to reduce symptoms of major depression in an open-label clinical trial. Accumulating evidence supports a role for nonpeptide CRF 1 receptor antagonists among the future pharmacotherapies for the treatment of depression.
Mice have paw preferences that are consistent upon repeated measurement. The Collins HI and LO st... more Mice have paw preferences that are consistent upon repeated measurement. The Collins HI and LO strains are two populations of mice that have been selectively bred to differ markedly in the degree of paw preference. They represent a unique genetic model of functional cerebral lateralization. Rotation (or circling) behavior in normal unlesioned animals reflects an endogenous lateralization of the functioning brain dopamine (DA) systems. In the present study, rotational behavior and lateralized brain DA neurochemistry were assessed in the Collins HI and LO strain mice. Confirming Collins findings, HI strain mice exhibited stronger paw preferences than LO strain mice. HI strain mice also showed stronger percent directional preferences during nocturnal tests of spontaneous rotation. Neurochemical differences were also apparent between the strains. DA and its metabolites were measured in the medial prefrontal cortex (PFC), nucleus accumbens (NAS), and striatum. Degrees of rotational and paw preference in HI, but not LO, mice were correlated with PFC asymmetries in DA and the DA metabolite dihydroxyphenyl acetic acid (DOPAC), respectively. Hemisphere, paw preference, turning preference, and strain interacted in a complex way to determine measures of DA utilization in the NAS and striatum. Even though the directions of paw preference and rotation were not correlated, HI and LO mice of differing paw and rotational directional preferences showed differences in DA neurochemistry in the NAS and striatum.
Foot-shock is used in a variety of behavioral tasks either as a motivational stimulus, a way to c... more Foot-shock is used in a variety of behavioral tasks either as a motivational stimulus, a way to characterize different rodents, or to test various pharmacological agents for their antinociceptive or analgesic effects. All these procedures need to assess foot-shock sensitivity either to rule out possible differences (when the shock is used as a motivational stimulus) or to use the differences to compare animals or treatments. In addition, many of the procedures that utilize foot-shock as a motivational stimulus evaluate freezing as an index of anxiety or fear. In the present study, data obtained by an automated computer system was compared with data obtained by human observers to validate the automated system for examining foot-shock sensitivity in mice. The different computer measures obtained for foot-shock sensitivity exhibited high correlations with human scoring at shock levels as low as 0.2 mA. The computer controlled analysis provided a non-subjective, quantifiable measurement of the foot-shock-induced response as well as freezing behavior. Automated data collection is an improvement over the methods of human visual observation in that the data collection is more standardized, efficient and consistent.
1966a, 1972b). Ayres labeled the theory sensory integration theory, the assessments she developed... more 1966a, 1972b). Ayres labeled the theory sensory integration theory, the assessments she developed tests of sensory integration, the clinical disorder sensory integration dysfunction, and the treatment she founded sensory integration treatment. Because the clinical and the neuroscience fi elds both use the term sensory integration, understanding the specifi c meanings intended by each fi eld is critical. This article focuses on clarifying the construct of sensory integration as used by the clinical fi eld and how translational research could elucidate the underlying neural mechanisms, objectify the diagnostic criteria, and support the evaluation of treatment effectiveness. Collaboration between clinical and basic sciences has the potential to improve the quality of life for those with SPD and their families, as well as provide insight into central nervous system functioning. CLINICAL FIELD RELATED TO SENSORY INTEGRATION DESCRIPTION OF THE DISORDER Sensory processing disorder is a heterogeneous condition that includes a variety of subtypes. Individuals with the disorder have impaired responses to, processing of, and/or organization of sensory information that effects participation in functional daily life routines and activities. Although the clinical fi eld is not completely unifi ed in how to defi ne the subtypes of SPD, a new nosology hypothesizes six subtypes (Miller, 2006; Miller et al., 2007a). Recent feature analysis and mathematical modeling sug
Children are being seen more readily by nurse practitioners when behavioral concerns arise. Atten... more Children are being seen more readily by nurse practitioners when behavioral concerns arise. Attentiondeficit/hyperactivity disorder (ADHD) is a common and costly behavioral condition seen by nurse practitioners. ADHD may also affect children's sensory processing. Symptoms of ADHD often include those of sensory processing dysfunction. Sensory processing disorder, a condition in which sensory processing dysfunction impacts everyday functioning, is a condition commonly seen with ADHD. For children with ADHD and associated conditions, it is important for nurse practitioners to be versed in conservative management of these conditions, including occupational therapy.
The effects of chronic administration of the antidepressant drugs desipramine, nortryptiline and ... more The effects of chronic administration of the antidepressant drugs desipramine, nortryptiline and paroxetine (PAR) (10 mg/kg/day, 21 days) on changes in turning (circling) behavior and on norepinephrine (NE), dopamine (DA) and serotonin and their metabolites 3,4-dihydroxyphenylacetic acid and 5-hydroxyindole acetic acid (5-HIAA) in the medial prefrontal cortex (PFC), nucleus aecumbens and striatum were evaluated in rats. All three drugs eliminated turning biases in right turning rats. All drugs increased DA concentrations in the PFC while PAR increased NE in the PFC and reduced 5-HIAA in all three structures. The results are discussed with reference to previous findings involving brain asymmetry in depression.
The development of selective corticotropin-releasing factor type-1 (CRF1) receptor antagonists re... more The development of selective corticotropin-releasing factor type-1 (CRF1) receptor antagonists represents a potential novel treatment for depression. These studies evaluated CRF1 receptor antagonists for antidepressant-like activity in mice. Subchronic dosing of both R 121919 (3-[6-(dimethylamino)-4-methyl-pyrid-3-yl]-2,5-dimethyl-N,N-dipropyl-pyrazolo[2,3-a]pyrimidin-7-amine) and DMP 696 (4-(1,3-dimethoxyprop-2-ylamino)-2,7-dimethyl-8-(2,4-dichlorophenyl)-pyrazolo[1,5-a]-1,3,5-triazine) significantly decreased immobility time in the tail suspension test (at 30 and at 3 and 10 mg/kg, i.p., respectively). These antidepressant-like effects were observed at doses that did not impair general locomotor activity. Neither antalarmin (N-butyl-N-ethyl-[2,5,6-trimethyl-7-(2,4,6)trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine) nor DMP 904 (4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine) had an effect indicative of antidepressant-like activity. These results suggest that the tail suspension assay may have utility to identify CRF1 receptor antagonists with antidepressant-like activity. Moreover, the results lend support to the theory that some nonpeptidic CRF1 receptor antagonists may possess antidepressant-like activity and therefore represent a promising novel pharmacotherapeutic strategy in the treatment of depression.
Background Medication and psychotherapy treatments for posttraumatic stress disorder (PTSD) provi... more Background Medication and psychotherapy treatments for posttraumatic stress disorder (PTSD) provide insufficient benefit for many patients. Substantial preclinical and clinical data indicate abnormalities in the hypothalamic-pituitary-adrenal axis, including signaling by corticotropin-releasing factor, in the pathophysiology of PTSD. Methods We conducted a double-blind, placebo-controlled, randomized, fixed-dose clinical trial evaluating the efficacy of GSK561679, a corticotropin-releasing factor receptor type 1 (CRF 1) antagonist in adult women with PTSD. The trial randomized 128 participants, of whom 96 completed the six-week treatment period. Results In both the intent-to-treat and completer samples, GSK561679 failed to show superiority over placebo on the primary outcome of change in Clinician Administered PTSD Scale total score. Adverse event frequencies did not significantly differ between GSK561679-and placebo-treated subjects. Exploration of the CRF 1 SNP rs110402 found response to GSK561679 and placebo did not significantly differ by genotype alone. However, subjects who had experienced a moderate or severe history of childhood abuse and who were also GG homozygotes for rs110402 showed significant improvement after treatment with GSK561679 (n=6) but not with placebo (n=7) on the PTSD Symptom Scale, Self-Report. Conclusions The results of this trial, the first evaluating a CRF 1 antagonist for the treatment of PTSD, combined with other negative trials of CRF 1 antagonists for major depressive disorder, generalized anxiety disorder, and
Children who are over-responsive to sensation have defensive and "fight or flight" reactions to o... more Children who are over-responsive to sensation have defensive and "fight or flight" reactions to ordinary levels of sensory stimulation in the environment. Based on clinical observations, sensory over-responsivity is hypothesized to reflect atypical neural integration of sensory input. To examine a possible underlying neural mechanism of the disorder, integration of simultaneous multisensory auditory and somatosensory stimulation was studied in twenty children with sensory over-responsivity (SOR) using event-related potentials (ERPs). Three types of sensory stimuli were presented and ERPs were recorded from thirty-two scalp electrodes while participants watched a silent cartoon: bilateral auditory clicks, right somatosensory median nerve electrical pulses, or both simultaneously. The paradigm was passive; no behavioral responses were required. To examine integration, responses to simultaneous multisensory auditory-somatosensory stimulation were compared to the sum of unisensory auditory plus unisensory somatosensory responses in four timewindows: (60-80 ms, 80-110 ms, 110-150 ms, and 180-220 ms). Specific midline and lateral electrode sites were examined over scalp regions where auditory-somatosensory integration was expected based on previous studies. Midline electrode sites (Fz, Cz, and Pz) showed significant integration during two time-windows: 60-80 ms and 180-220 ms. Significant integration was also found at contralateral electrode site (C3) for the timewindow between 180 and 220 ms. At ipsilateral electrode sites (C4 and CP6), no significant integration was found during any of the time-windows (i.e. the multisensory ERP was not significantly different from the summed unisensory ERP). These results demonstrate that MSI can be reliably measured in children with SOR and provide evidence that multisensory auditory-somatosensory input is integrated during both early and later stages of sensory information processing, mainly over fronto-central scalp regions.
Fragile X syndrome, a form of mental retardation caused by inadequate levels of fragile X mental ... more Fragile X syndrome, a form of mental retardation caused by inadequate levels of fragile X mental retardation protein (FMRP), is characterized by extreme sensitivity to sensory stimuli and increased behavioral and hormonal reactivity to stressors. Fmr1 knockout mice lack FMRP and exhibit abnormal responses to auditory stimuli. This study sought to determine whether Fmr1 knockout mice on an F1 hybrid background are normal in their response to footshock. Knockout mice were also examined for signs of hyperexcitation across an extended trial range, and serum corticosterone levels were evaluated in response to various stressors. The ability to acquire conditioned taste aversion was also assessed. Knockout mice exhibited no impairment in associative aversive learning or memory, since they successfully expressed conditioned taste aversion. Footshock-sensitivity, freezing behavior, and corticosterone response to various stressors did not differ between knockout and wild-type mice. However, knockout mice exhibited significantly increased responses during the extended test. The knockout mice's increased responsiveness to footshock in the extended test may be an indication of increased vulnerability to stress or enhanced emotional reactivity.
Foot-shock is used in a variety of behavioral tasks either as a motivational stimulus, a way to c... more Foot-shock is used in a variety of behavioral tasks either as a motivational stimulus, a way to characterize different rodents, or to test various pharmacological agents for their antinociceptive or analgesic effects. All these procedures need to assess foot-shock sensitivity either to rule out possible differences (when the shock is used as a motivational stimulus) or to use the differences to compare animals or treatments. In addition, many of the procedures that utilize foot-shock as a motivational stimulus evaluate freezing as an index of anxiety or fear. In the present study, data obtained by an automated computer system was compared with data obtained by human observers to validate the automated system for examining foot-shock sensitivity in mice. The different computer measures obtained for foot-shock sensitivity exhibited high correlations with human scoring at shock levels as low as 0.2 mA. The computer controlled analysis provided a non-subjective, quantifiable measurement of the foot-shock-induced response as well as freezing behavior. Automated data collection is an improvement over the methods of human visual observation in that the data collection is more standardized, efficient and consistent.
Sensory modulation disorder (SMD) is a severe inability to regulate responses to everyday sensory... more Sensory modulation disorder (SMD) is a severe inability to regulate responses to everyday sensory stimulation to which most people easily adapt. It is estimated to affect 5% to 16% of the general population of children. Although heterogeneity is seen in the presentation clinically, previous research has not empirically investigated whether the clinical heterogeneity of SMD can be classified into subtypes. This study explores a cohort of 98 children identified with SMD at the Department of Pediatric Rehabilitation by a member of the occupational therapy team at The Children's Hospital of Denver. Two subtypes of SMD were identified through cluster analysis based on data from 4 parent-report instruments. The first subtype is characterized by sensory seeking/craving, hyperactive, impulsive, externalizing (eg, delinquent, aggressive), unsocial, inadaptive, and impaired cognitive/social behavior. The second subtype is characterized by movement sensitivity, emotionally withdrawal, and low energy/weak behavior. Findings from this study present a step toward understanding and classifying the complexities of children with SMDs.
Spontaneous turning behavior and locomotor activity were evaluated for their ability to predict d... more Spontaneous turning behavior and locomotor activity were evaluated for their ability to predict differences in the voluntary consumption of ethanol in male Long-Evans rats. Animals were assessed for their preferred direction of turning behavior and for high vs. low levels of spontaneous locomotor activity, as determined during nocturnal testing in a rotometer. Subsequently, preference for a 10% ethanol solution vs. water was determined in a 24-h two-bottle home-cage free-choice paradigm. Rats exhibiting a right-turning preference consumed more ethanol than rats showing a left-turning preference. While locomotor activity alone did not predict differences in drinking, turning and locomotor activity together predicted differences in ethanol consumption. Low-activity right-turning rats consumed more ethanol than all the other groups of rats. Previous studies from this laboratory have shown that individual differences in turning behavior are accompanied by different asymmetries in dopamine (DA) function in the medial prefrontal cortex (mPFC). Individual differences in locomotor activity are associated with differences in nucleus accumbens (NAS) DA function. The present data suggest that variations in mPFC DA asymmetry and NAS DA function may underlie differences in the voluntary consumption of ethanol.
Ž. Ž. Ž. Ethanol 0.5 grkg i.p. 15 min prior to sacrifice increased homovanillic acid HVA levels i... more Ž. Ž. Ž. Ethanol 0.5 grkg i.p. 15 min prior to sacrifice increased homovanillic acid HVA levels in the left medial prefrontal cortex mPFC Ž. Ž. of left-turning rats and in the right mPFC of right-turning rats. In the nucleus accumbens NAS , ethanol decreased dopamine DA , Ž. 3,4-dihydroxyphenylacetic acid DOPAC , and HVA levels in rats that exhibited low levels of locomotor activity but not in rats that exhibited high levels of locomotor activity. This laboratory has previously shown that rats exhibiting differences in turning and locomotor activity behavior display different preferences for ethanol. The present results suggest that ethanol-induced differences in mPFC and NAS DA activity may be related to individual differences in the susceptibility to abuse ethanol.
Research in Developmental Disabilities, May 1, 2012
Attention deficit hyperactivity disorder (ADHD) is an early childhood developmental disorder that... more Attention deficit hyperactivity disorder (ADHD) is an early childhood developmental disorder that has received enormous attention in research. Typical characteristics of ADHD are developmentally inappropriate impulsivity, inattention, and hyperactivity (Barkley & Murphy, 1998; Kaplan, Sadock, & Grebb, 1994). ADHD is a costly and prevalent childhood disorder that affects 3-12% of school-aged children (
How can measuring children’s Electrodermal Activity (EDA) help improve the design of an occupatio... more How can measuring children’s Electrodermal Activity (EDA) help improve the design of an occupational therapy experience? Twenty-two children with sensory challenges such as Autism and ADHD participated in the study. Children attended occupational therapy as usual, while their physiological arousal (i.e., EDA) was measured with a wireless device on the bottom calf. Combining the EDA signal with video, researchers could better understand the emotional experience of therapy. All 22 children were able to wear the portable EDA sensors throughout the vigorous activities with minimal impact. Five insights generated from these observations are described in detail, with emphasis on how therapists used the findings to re-design their therapeutic process. This paper demonstrates how the ambulatory measurement of EDA can directly help with the emotional design of therapeutic services.
Fragile X syndrome, a form of mental retardation caused by inadequate levels of fragile X mental ... more Fragile X syndrome, a form of mental retardation caused by inadequate levels of fragile X mental retardation protein (FMRP), is characterized by extreme sensitivity to sensory stimuli and increased behavioral and hormonal reactivity to stressors. Fmr1 knockout mice lack FMRP and exhibit abnormal responses to auditory stimuli. This study sought to determine whether Fmr1 knockout mice on an F1 hybrid background are normal in their response to footshock. Knockout mice were also examined for signs of hyperexcitation across an extended trial range, and serum corticosterone levels were evaluated in response to various stressors. The ability to acquire conditioned taste aversion was also assessed. Knockout mice exhibited no impairment in associative aversive learning or memory, since they successfully expressed conditioned taste aversion. Footshock-sensitivity, freezing behavior, and corticosterone response to various stressors did not differ between knockout and wild-type mice. However, knockout mice exhibited significantly increased responses during the extended test. The knockout mice's increased responsiveness to footshock in the extended test may be an indication of increased vulnerability to stress or enhanced emotional reactivity.
Corticotropin-releasing factor (CRF) is a neuropeptide that plays a primary role in the neuroendo... more Corticotropin-releasing factor (CRF) is a neuropeptide that plays a primary role in the neuroendocrine, autonomic, and behavioral responses to stressors. Numerous reports suggest that alterations in CRF function contribute to the pathogenesis of depression. Recently, selective nonpeptide CRF type 1 (CRF 1) receptor antagonists have been discovered and several of these CRF 1 receptor antagonists have demonstrated antidepressantlike efficacy in animals. The CRF 1 receptor antagonists appear to be unique, as they exhibit antidepressant-like activity principally in animal models that are hyperresponsive to stress or under experimental conditions that alter endogenous stress-hormone activity. A nonpeptide CRF 1 receptor antagonist has also been shown to reduce symptoms of major depression in an open-label clinical trial. Accumulating evidence supports a role for nonpeptide CRF 1 receptor antagonists among the future pharmacotherapies for the treatment of depression.
Mice have paw preferences that are consistent upon repeated measurement. The Collins HI and LO st... more Mice have paw preferences that are consistent upon repeated measurement. The Collins HI and LO strains are two populations of mice that have been selectively bred to differ markedly in the degree of paw preference. They represent a unique genetic model of functional cerebral lateralization. Rotation (or circling) behavior in normal unlesioned animals reflects an endogenous lateralization of the functioning brain dopamine (DA) systems. In the present study, rotational behavior and lateralized brain DA neurochemistry were assessed in the Collins HI and LO strain mice. Confirming Collins findings, HI strain mice exhibited stronger paw preferences than LO strain mice. HI strain mice also showed stronger percent directional preferences during nocturnal tests of spontaneous rotation. Neurochemical differences were also apparent between the strains. DA and its metabolites were measured in the medial prefrontal cortex (PFC), nucleus accumbens (NAS), and striatum. Degrees of rotational and paw preference in HI, but not LO, mice were correlated with PFC asymmetries in DA and the DA metabolite dihydroxyphenyl acetic acid (DOPAC), respectively. Hemisphere, paw preference, turning preference, and strain interacted in a complex way to determine measures of DA utilization in the NAS and striatum. Even though the directions of paw preference and rotation were not correlated, HI and LO mice of differing paw and rotational directional preferences showed differences in DA neurochemistry in the NAS and striatum.
Foot-shock is used in a variety of behavioral tasks either as a motivational stimulus, a way to c... more Foot-shock is used in a variety of behavioral tasks either as a motivational stimulus, a way to characterize different rodents, or to test various pharmacological agents for their antinociceptive or analgesic effects. All these procedures need to assess foot-shock sensitivity either to rule out possible differences (when the shock is used as a motivational stimulus) or to use the differences to compare animals or treatments. In addition, many of the procedures that utilize foot-shock as a motivational stimulus evaluate freezing as an index of anxiety or fear. In the present study, data obtained by an automated computer system was compared with data obtained by human observers to validate the automated system for examining foot-shock sensitivity in mice. The different computer measures obtained for foot-shock sensitivity exhibited high correlations with human scoring at shock levels as low as 0.2 mA. The computer controlled analysis provided a non-subjective, quantifiable measurement of the foot-shock-induced response as well as freezing behavior. Automated data collection is an improvement over the methods of human visual observation in that the data collection is more standardized, efficient and consistent.
1966a, 1972b). Ayres labeled the theory sensory integration theory, the assessments she developed... more 1966a, 1972b). Ayres labeled the theory sensory integration theory, the assessments she developed tests of sensory integration, the clinical disorder sensory integration dysfunction, and the treatment she founded sensory integration treatment. Because the clinical and the neuroscience fi elds both use the term sensory integration, understanding the specifi c meanings intended by each fi eld is critical. This article focuses on clarifying the construct of sensory integration as used by the clinical fi eld and how translational research could elucidate the underlying neural mechanisms, objectify the diagnostic criteria, and support the evaluation of treatment effectiveness. Collaboration between clinical and basic sciences has the potential to improve the quality of life for those with SPD and their families, as well as provide insight into central nervous system functioning. CLINICAL FIELD RELATED TO SENSORY INTEGRATION DESCRIPTION OF THE DISORDER Sensory processing disorder is a heterogeneous condition that includes a variety of subtypes. Individuals with the disorder have impaired responses to, processing of, and/or organization of sensory information that effects participation in functional daily life routines and activities. Although the clinical fi eld is not completely unifi ed in how to defi ne the subtypes of SPD, a new nosology hypothesizes six subtypes (Miller, 2006; Miller et al., 2007a). Recent feature analysis and mathematical modeling sug
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