Craig McDonald | George Mason University (original) (raw)
Papers by Craig McDonald
Neuroscience, Jul 31, 2017
Nicotine is one of the most addictive substances known, targeting multiple memory systems, includ... more Nicotine is one of the most addictive substances known, targeting multiple memory systems, including the ventral and dorsal striatum. One form of neuroplasticity commonly associated with nicotine is dendrite remodeling. Nicotine-induced dendritic remodeling of ventral striatal medium spiny neurons (MSNs) is well-documented. Whether MSN dendrites in the dorsal striatum undergo a similar pattern of nicotine-induced structural remodeling is unknown. A morphometric analysis of Golgi-stained MSNs in rat revealed a natural asymmetry in dendritic morphology across the mediolateral axis, with larger, more complex MSNs found in the dorsolateral striatum (DLS). Chronic nicotine produced a lasting (21day) expansion in the dendritic complexity of MSNs in the DLS, but not dorsomedial striatum (DMS). Given prior evidence that MSN subtypes can be distinguished based on dendritic morphology, MSNs were segregated into morphological subpopulations based on the number of primary dendrites. Analysis of...
Psychophysiology, 2010
In attended novelty oddball tasks, rare nontarget stimuli can elicit two late positive ERP compon... more In attended novelty oddball tasks, rare nontarget stimuli can elicit two late positive ERP components: P3a and P300. In passive oddball tasks, P300 is not elicited by these stimuli. In passive tasks, however, P3a is accompanied by another positive component, termed eP3a, which may have evaded detection in attended oddball tasks because of its spatiotemporal overlap with P300. To address this, temporal-spatial principal components analysis was used to quantify ERPs recorded in attended three-tone and novelty oddball tasks. As expected, novel stimuli elicited both P3a and P300. The analysis also identified a third component, evident in novelty ERPs as an inflection on the leading edge of P3a. This component has the same antecedent conditions as P3a, but is earlier and more centrally distributed. Its spatiotemporal characteristics suggest that it may be the eP3a component recently described in passive oddball tasks.
We examinedwhether the utility of a recently developed auditory probe technique for indexing cogn... more We examinedwhether the utility of a recently developed auditory probe technique for indexing cognitiveworkload
was dependent on the stimulus properties of the probes. EEG was recorded while participants played a
videogame under various levels of cognitive workload. At each level of workload, participants were probed
with one of four different types of auditory stimuli: novel complex, repeated complex, novel simple, or repeated
simple sounds. Probe efficacy at indexing cognitiveworkloadwas assessed by determiningwhich probes elicited
ERP components that decreased monotonically as a function of workload. Results suggest that complex auditory
stimuliwere significantly more effective in indexing cognitiveworkload than simple stimuli. The efficacy of complex
stimuli was due to their ability to elicit a robust orienting response, indexed by the early P3a component of
the ERP, which decreased monotonically as a function of cognitive workload.
American Journal of Hospice & Palliative Medicine, 2010
Neuroscience and biobehavioral reviews, Jan 2, 2015
Smith, R.F., McDonald, C.G., Bergstrom, H.C., Ehlinger, D.G., and Brielmaier, J. M. Adolescent ni... more Smith, R.F., McDonald, C.G., Bergstrom, H.C., Ehlinger, D.G., and Brielmaier, J. M. Adolescent nicotine induces persisting changes in development of neural connectivity. NEUROSCI BIOBEHAV REV. A large number of brain changes occur during adolescence as the CNS matures. These changes suggest that the adolescent brain may still be susceptible to developmental alterations by substances which impact its growth. Here we review recent studies on adolescent nicotine which show that the adolescent brain is differentially sensitive to nicotine-induced alterations in dendritic elaboration, in several brain areas associated with processing reinforcement and emotion, specifically including nucleus accumbens, medial prefrontal cortex, basolateral amygdala, bed nucleus of the stria terminalis, and dentate gyrus. Both sensitivity to nicotine, and specific areas responding to nicotine, differ between adolescent and adult rats, and dendritic changes in response to adolescent nicotine persist into ad...
Proceedings of the National Academy of Sciences of the United States of America, Jan 26, 2015
Serum biomarkers in Duchenne muscular dystrophy (DMD) may provide deeper insights into disease pa... more Serum biomarkers in Duchenne muscular dystrophy (DMD) may provide deeper insights into disease pathogenesis, suggest new therapeutic approaches, serve as acute read-outs of drug effects, and be useful as surrogate outcome measures to predict later clinical benefit. In this study a large-scale biomarker discovery was performed on serum samples from patients with DMD and age-matched healthy volunteers using a modified aptamer-based proteomics technology. Levels of 1,125 proteins were quantified in serum samples from two independent DMD cohorts: cohort 1 (The Parent Project Muscular Dystrophy-Cincinnati Children's Hospital Medical Center), 42 patients with DMD and 28 age-matched normal volunteers; and cohort 2 (The Cooperative International Neuromuscular Research Group, Duchenne Natural History Study), 51 patients with DMD and 17 age-matched normal volunteers. Forty-four proteins showed significant differences that were consistent in both cohorts when comparing DMD patients and hea...
American Journal of Physical Medicine & Rehabilitation
Forty-five individuals with spinal muscular atrophy (SMA) types II and III were evaluated prospec... more Forty-five individuals with spinal muscular atrophy (SMA) types II and III were evaluated prospectively over a 10-yr period to develop an impairment and disability profile. SMA II subjects showed marked weakness and progressive decline of strength. Mean manual muscle test (MMT) score for all muscles combined was 2.3 +/- 0.6, with a decline in strength of -0.24 MMT units per decade. SMA III individuals had a relatively static or very slowly progressive course and were far stronger. Mean MMT score for all muscles combined was 3.8 +/- 0.7, and the decline in strength per decade was not significant. In both types proximal weakness was greater than distal, but there was greater involvement of the lower extremities and the extensor muscle groups only in SMA II. Contractures, progressive scoliosis, and restrictive lung disease (RLD) were present in most of the SMA II individuals, but these complications were rare in SMA III. Maximal expiratory pressures were affected earlier and to a great...
American Journal of Physical Medicine & Rehabilitation
Carter GT, Abresch RT, Fowler WM Jr, Johnson ER, Kilmer DD, McDonald CM: Profiles of neuromuscula... more Carter GT, Abresch RT, Fowler WM Jr, Johnson ER, Kilmer DD, McDonald CM: Profiles of neuromuscular diseases: spinal muscular atrophy. Am J Phys Med Rehabil 1995;74(Suppl):S150-S159 Forty-five individuals with spinal muscular atrophy (SMA) types II and III were evaluated prospectively over a 10-yr period to develop an impairment and disability profile. SMA II subjects showed marked weakness and progressive decline of strength. Mean manual muscle test (MMT) score for all muscles combined was 2.3 +/- 0.6, with a decline in strength of -0.24 MMT units per decade. SMA III individuals had a relatively static or very slowly progressive course and were far stronger. Mean MMT score for all muscles combined was 3.8 +/- 0.7, and the decline in strength per decade was not significant. In both types proximal weakness was greater than distal, but there was greater involvement of the lower extremities and the extensor muscle groups only in SMA II. Contractures, progressive scoliosis, and restricti...
The journal of spinal cord medicine
Determine the effects of a nutrition education and exercise intervention on the health and fitnes... more Determine the effects of a nutrition education and exercise intervention on the health and fitness of adolescents with mobility impairment due to spinal cord dysfunction from myelomeningocele and spinal cord injury. Subjects participated in a 16-week intervention consisting of a behavioral approach to lifestyle change, exercise, and nutrition education to improve fitness (BENEfit) program. Participants were given a schedule of aerobic and strengthening exercises and attended nutrition education and behavior modification sessions every other week along with their parent(s). Twenty adolescents (aged 11-18 years, mean 15.4 +/- 2.2 years) with spinal cord dysfunction. Subjects were tested immediately prior to starting and upon completion of the program. Aerobic fitness was measured using a ramp protocol with an arm ergometer. Heart rate and oxygen uptake were measured. Values at anaerobic threshold and maximum oxygen uptake were recorded. Peak isokinetic arm and shoulder strength were d...
Behavioural brain research, Jan 20, 2015
Adolescent cigarette use is associated with reduced quitting success and continued smoking in adu... more Adolescent cigarette use is associated with reduced quitting success and continued smoking in adulthood. Interestingly, polymorphisms of the dopamine D3 receptor (DRD3) gene have been associated with smoking behavior, and the receptor is expressed in an age- and brain region-dependent manner that suggests relevance to addiction. Here we investigate the possible role of dopamine-related receptors, including DRD3 and an intriguing splice variant known as D3nf, in nicotine-induced sensitization. In adolescent and adult male rats, we examined 1) alterations occurring in dopamine receptor-related mRNAs (DRD1, DRD2, DRD3 and D3nf) at two time points during a sensitizing-regimen of nicotine and 2) whether DRD3 antagonism either during the initial treatment (induction) or at a later challenge exposure (expression) is able to block nicotine sensitization. Nicotine-induced changes were seen for DRD3 and D3nf mRNAs in the nucleus accumbens shell early in repeated exposure in both age groups. D...
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography, Jan 21, 2015
Cardiac disease is a major cause of death in patients with muscular dystrophies. The use of feasi... more Cardiac disease is a major cause of death in patients with muscular dystrophies. The use of feasible and reproducible echocardiographic measures of cardiac function is critical to advance the field of therapeutics for dystrophic cardiomyopathy. Participants aged 8 to 18 years with genetically confirmed Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, or limb-girdle muscular dystrophy were enrolled at five centers, and standardized echocardiographic examinations were performed. Measures of systolic and diastolic function and speckle-tracking echocardiography-derived cardiac strain were reviewed independently by two central readers. Furthermore, echocardiographic measures from participants with DMD were compared with those from retrospective age-matched control subjects from a single site to assess measures of myocardial function. Forty-eight participants (mean age, 13.3 ± 2.7 years) were enrolled. Shortening fraction had a greater interobserver correlation (intraclass co...
Lancet, Jan 20, 2015
Cardiorespiratory failure is the leading cause of death in Duchenne muscular dystrophy. Based on ... more Cardiorespiratory failure is the leading cause of death in Duchenne muscular dystrophy. Based on preclinical and phase 2 evidence, we assessed the efficacy and safety of idebenone in young patients with Duchenne muscular dystrophy who were not taking concomitant glucocorticoids. In a multicentre phase 3 trial in Belgium, Germany, the Netherlands, Switzerland, France, Sweden, Austria, Italy, Spain, and the USA, patients (age 10-18 years old) with Duchenne muscular dystrophy were randomly assigned in a one-to-one ratio with a central interactive web response system with a permuted block design with four patients per block to receive idebenone (300 mg three times a day) or matching placebo orally for 52 weeks. Study personnel and patients were masked to treatment assignment. The primary endpoint was change in peak expiratory flow (PEF) as percentage predicted (PEF%p) from baseline to week 52, measured with spirometry. Analysis was by intention to treat (ITT) and a modified ITT (mITT), ...
Vision research, 1999
Although color-opponent neurons appear to subserve color vision, precisely how these cells encode... more Although color-opponent neurons appear to subserve color vision, precisely how these cells encode hue is still not clear. Single-unit, extracellular recordings from the rainbow trout optic tectum were made in order to examine the possible role of action potential timing in coding chromatic stimuli. We found that color-opponent units can exhibit differences in response latency which are a function of wavelength and response sign, with the OFF response exhibiting the shorter response latency. We also found that units often responded with spike bursts characterized by early and late spikes separated by a silent period, with the relative proportion of early and late spikes varying as a function of wavelength. This type of discharge pattern appears to be a result of inhibitory, color-opponent processes. We suggest that complete inhibition of early spikes may be the mechanism underlying the observed latency differences. These findings suggest a role for action potential patterning in codi...
Brain structure & function, Jan 26, 2014
Chronic nicotine exposure during adolescence induces dendritic remodeling of medium spiny neurons... more Chronic nicotine exposure during adolescence induces dendritic remodeling of medium spiny neurons (MSNs) in the nucleus accumbens (NAcc) shell. While nicotine-induced dendritic remodeling has frequently been described as persistent, the trajectory of dendrite remodeling is unknown. Specifically, no study to date has characterized the structural plasticity of dendrites in the NAcc immediately following chronic nicotine, leaving open the possibility that dendrite remodeling emerges gradually over time. Further, the neuropharmacological mechanisms through which nicotine induces dendrite remodeling are not well understood. To address these questions, rats were co-administered chronic nicotine (0.5 mg/kg) and the D1-dopamine receptor (D1DR) antagonist SCH-23390 (0.05 mg/kg) subcutaneously every other day during adolescence. Brains were then processed for Golgi-Cox staining either 1 day or 21 days following drug exposure and dendrites from MSNs in the NAcc shell digitally reconstructed in...
The journal of spinal cord medicine, 2007
To compare body composition in patients aged 11 to 21 years with spinal dysfunction due to spinal... more To compare body composition in patients aged 11 to 21 years with spinal dysfunction due to spinal cord injury (SCI) and spina bifida (SB) vs. able-bodied control (CTRL) and able-bodied overweight (OW) groups and to examine the relationships between resting energy expenditure (REE) and total lean mass (TLM) in the SCI, SB, CTRL, and OW groups. Two hundred fifteen subjects, including 85 CTRL, 31 OW, 33 SCI, and 66 SB, were evaluated. Body composition was estimated by dual energy x-ray absorptiometry (DXA). Measurements included height, weight, total lean mass (TLM), fat tissue mass (FTM), body mass index (BMI), BMI percentile (BMI%tile), and % fat. Resting energy measurements were obtained in fasting subjects with an open-circuit indirect calorimeter. There were gender differences in height, weight, BMI, TLM, fat mass, % fat, and REE. The REE in the SCI and SB groups was significantly different from that in the CTRL and OW groups, but no significant difference was found between the SC...
American journal of physical medicine & rehabilitation / Association of Academic Physiatrists
Fifteen subjects with Becker's muscular dystrophy (BMD) were studied prospectively over a 10-... more Fifteen subjects with Becker's muscular dystrophy (BMD) were studied prospectively over a 10-yr period to provide a profile of impairment and disability. Proximal lower extremity musculature (particularly the hip and knee extensors), ankle dorsiflexors, and neck flexors showed significantly early weakness. Extensor muscle groups were weaker than flexor muscles at the elbow and knee. The mean manual muscle test (MMT) strength grade for all muscle groups combined was 3.7 +/- 0.8 MMT units. There was a slowly progressive decline in strength, only -0.31 MMT units per decade, and the decline was relatively equal in all muscle groups. There was not side dominance. Severe contractures did not appear to be a problem until after transition to a wheelchair, and scoliosis was rare. Restrictive lung disease occurred as a late complication in a small percentage of cases; however, maximal expiratory pressure was significantly reduced early in the disease. Only two individuals (19%) had severe...
American journal of physical medicine & rehabilitation / Association of Academic Physiatrists
One hundred and sixty-two patients with Duchenne muscular dystrophy (DMD) were followed over a 10... more One hundred and sixty-two patients with Duchenne muscular dystrophy (DMD) were followed over a 10-yr period to provide a profile of impairment and disability. The median height and weight of DMD boys were normally distributed before ages 9-10, but during the second decade height was markedly reduced, and weight was no longer normally distributed. Younger boys gained more weight than normals, whereas older individuals actually showed weight loss. Manual muscle test (MMT) measurements showed loss of strength in a fairly linear fashion from ages 5-13 yr, -0.25 MMT units per year. Upper extremity muscles were stronger than lower extremity muscles, proximal muscle groups were weaker than distal muscle groups, and extensor muscles were weaker than flexor muscles. There was no side dominance. There was a change in the rate of strength loss at 14-15 yr, and the decline slowed to only -0.06 MMT units per year. Although MMT and quantitative strength measurement profiles were similar, the latt...
American journal of physical medicine & rehabilitation / Association of Academic Physiatrists
Data were collected prospectively for an impairment and disability profile for 86 hereditary moto... more Data were collected prospectively for an impairment and disability profile for 86 hereditary motor and sensory neuropathy, types I and II (HMSN) subjects over a 10-yr period. Our data confirm that HMSN is a slowly progressive disorder that has a very heterogeneous phenotypical expression. The disorder was characterized primarily by diffuse muscle weakness with prominent distal atrophy. The mean manual muscle test (MMT) strength grade for all muscle groups combined was 3.9 +/- 0.7 MMT units. There was a slowly progressive decline in strength, only -0.15 MMT units per decade. Distal muscle groups were weaker than proximal muscles, and the decline in strength of the ankle muscles was greater than for the proximal muscles. There was no side dominance. Anthropometric data revealed that distal atrophy may be masked by subcutaneous fat in female subjects. On average, HMSN subjects produced 20-40% less force than normal controls, using quantitative isometric and isokinetic strength measures...
Neuroscience, Jul 31, 2017
Nicotine is one of the most addictive substances known, targeting multiple memory systems, includ... more Nicotine is one of the most addictive substances known, targeting multiple memory systems, including the ventral and dorsal striatum. One form of neuroplasticity commonly associated with nicotine is dendrite remodeling. Nicotine-induced dendritic remodeling of ventral striatal medium spiny neurons (MSNs) is well-documented. Whether MSN dendrites in the dorsal striatum undergo a similar pattern of nicotine-induced structural remodeling is unknown. A morphometric analysis of Golgi-stained MSNs in rat revealed a natural asymmetry in dendritic morphology across the mediolateral axis, with larger, more complex MSNs found in the dorsolateral striatum (DLS). Chronic nicotine produced a lasting (21day) expansion in the dendritic complexity of MSNs in the DLS, but not dorsomedial striatum (DMS). Given prior evidence that MSN subtypes can be distinguished based on dendritic morphology, MSNs were segregated into morphological subpopulations based on the number of primary dendrites. Analysis of...
Psychophysiology, 2010
In attended novelty oddball tasks, rare nontarget stimuli can elicit two late positive ERP compon... more In attended novelty oddball tasks, rare nontarget stimuli can elicit two late positive ERP components: P3a and P300. In passive oddball tasks, P300 is not elicited by these stimuli. In passive tasks, however, P3a is accompanied by another positive component, termed eP3a, which may have evaded detection in attended oddball tasks because of its spatiotemporal overlap with P300. To address this, temporal-spatial principal components analysis was used to quantify ERPs recorded in attended three-tone and novelty oddball tasks. As expected, novel stimuli elicited both P3a and P300. The analysis also identified a third component, evident in novelty ERPs as an inflection on the leading edge of P3a. This component has the same antecedent conditions as P3a, but is earlier and more centrally distributed. Its spatiotemporal characteristics suggest that it may be the eP3a component recently described in passive oddball tasks.
We examinedwhether the utility of a recently developed auditory probe technique for indexing cogn... more We examinedwhether the utility of a recently developed auditory probe technique for indexing cognitiveworkload
was dependent on the stimulus properties of the probes. EEG was recorded while participants played a
videogame under various levels of cognitive workload. At each level of workload, participants were probed
with one of four different types of auditory stimuli: novel complex, repeated complex, novel simple, or repeated
simple sounds. Probe efficacy at indexing cognitiveworkloadwas assessed by determiningwhich probes elicited
ERP components that decreased monotonically as a function of workload. Results suggest that complex auditory
stimuliwere significantly more effective in indexing cognitiveworkload than simple stimuli. The efficacy of complex
stimuli was due to their ability to elicit a robust orienting response, indexed by the early P3a component of
the ERP, which decreased monotonically as a function of cognitive workload.
American Journal of Hospice & Palliative Medicine, 2010
Neuroscience and biobehavioral reviews, Jan 2, 2015
Smith, R.F., McDonald, C.G., Bergstrom, H.C., Ehlinger, D.G., and Brielmaier, J. M. Adolescent ni... more Smith, R.F., McDonald, C.G., Bergstrom, H.C., Ehlinger, D.G., and Brielmaier, J. M. Adolescent nicotine induces persisting changes in development of neural connectivity. NEUROSCI BIOBEHAV REV. A large number of brain changes occur during adolescence as the CNS matures. These changes suggest that the adolescent brain may still be susceptible to developmental alterations by substances which impact its growth. Here we review recent studies on adolescent nicotine which show that the adolescent brain is differentially sensitive to nicotine-induced alterations in dendritic elaboration, in several brain areas associated with processing reinforcement and emotion, specifically including nucleus accumbens, medial prefrontal cortex, basolateral amygdala, bed nucleus of the stria terminalis, and dentate gyrus. Both sensitivity to nicotine, and specific areas responding to nicotine, differ between adolescent and adult rats, and dendritic changes in response to adolescent nicotine persist into ad...
Proceedings of the National Academy of Sciences of the United States of America, Jan 26, 2015
Serum biomarkers in Duchenne muscular dystrophy (DMD) may provide deeper insights into disease pa... more Serum biomarkers in Duchenne muscular dystrophy (DMD) may provide deeper insights into disease pathogenesis, suggest new therapeutic approaches, serve as acute read-outs of drug effects, and be useful as surrogate outcome measures to predict later clinical benefit. In this study a large-scale biomarker discovery was performed on serum samples from patients with DMD and age-matched healthy volunteers using a modified aptamer-based proteomics technology. Levels of 1,125 proteins were quantified in serum samples from two independent DMD cohorts: cohort 1 (The Parent Project Muscular Dystrophy-Cincinnati Children's Hospital Medical Center), 42 patients with DMD and 28 age-matched normal volunteers; and cohort 2 (The Cooperative International Neuromuscular Research Group, Duchenne Natural History Study), 51 patients with DMD and 17 age-matched normal volunteers. Forty-four proteins showed significant differences that were consistent in both cohorts when comparing DMD patients and hea...
American Journal of Physical Medicine & Rehabilitation
Forty-five individuals with spinal muscular atrophy (SMA) types II and III were evaluated prospec... more Forty-five individuals with spinal muscular atrophy (SMA) types II and III were evaluated prospectively over a 10-yr period to develop an impairment and disability profile. SMA II subjects showed marked weakness and progressive decline of strength. Mean manual muscle test (MMT) score for all muscles combined was 2.3 +/- 0.6, with a decline in strength of -0.24 MMT units per decade. SMA III individuals had a relatively static or very slowly progressive course and were far stronger. Mean MMT score for all muscles combined was 3.8 +/- 0.7, and the decline in strength per decade was not significant. In both types proximal weakness was greater than distal, but there was greater involvement of the lower extremities and the extensor muscle groups only in SMA II. Contractures, progressive scoliosis, and restrictive lung disease (RLD) were present in most of the SMA II individuals, but these complications were rare in SMA III. Maximal expiratory pressures were affected earlier and to a great...
American Journal of Physical Medicine & Rehabilitation
Carter GT, Abresch RT, Fowler WM Jr, Johnson ER, Kilmer DD, McDonald CM: Profiles of neuromuscula... more Carter GT, Abresch RT, Fowler WM Jr, Johnson ER, Kilmer DD, McDonald CM: Profiles of neuromuscular diseases: spinal muscular atrophy. Am J Phys Med Rehabil 1995;74(Suppl):S150-S159 Forty-five individuals with spinal muscular atrophy (SMA) types II and III were evaluated prospectively over a 10-yr period to develop an impairment and disability profile. SMA II subjects showed marked weakness and progressive decline of strength. Mean manual muscle test (MMT) score for all muscles combined was 2.3 +/- 0.6, with a decline in strength of -0.24 MMT units per decade. SMA III individuals had a relatively static or very slowly progressive course and were far stronger. Mean MMT score for all muscles combined was 3.8 +/- 0.7, and the decline in strength per decade was not significant. In both types proximal weakness was greater than distal, but there was greater involvement of the lower extremities and the extensor muscle groups only in SMA II. Contractures, progressive scoliosis, and restricti...
The journal of spinal cord medicine
Determine the effects of a nutrition education and exercise intervention on the health and fitnes... more Determine the effects of a nutrition education and exercise intervention on the health and fitness of adolescents with mobility impairment due to spinal cord dysfunction from myelomeningocele and spinal cord injury. Subjects participated in a 16-week intervention consisting of a behavioral approach to lifestyle change, exercise, and nutrition education to improve fitness (BENEfit) program. Participants were given a schedule of aerobic and strengthening exercises and attended nutrition education and behavior modification sessions every other week along with their parent(s). Twenty adolescents (aged 11-18 years, mean 15.4 +/- 2.2 years) with spinal cord dysfunction. Subjects were tested immediately prior to starting and upon completion of the program. Aerobic fitness was measured using a ramp protocol with an arm ergometer. Heart rate and oxygen uptake were measured. Values at anaerobic threshold and maximum oxygen uptake were recorded. Peak isokinetic arm and shoulder strength were d...
Behavioural brain research, Jan 20, 2015
Adolescent cigarette use is associated with reduced quitting success and continued smoking in adu... more Adolescent cigarette use is associated with reduced quitting success and continued smoking in adulthood. Interestingly, polymorphisms of the dopamine D3 receptor (DRD3) gene have been associated with smoking behavior, and the receptor is expressed in an age- and brain region-dependent manner that suggests relevance to addiction. Here we investigate the possible role of dopamine-related receptors, including DRD3 and an intriguing splice variant known as D3nf, in nicotine-induced sensitization. In adolescent and adult male rats, we examined 1) alterations occurring in dopamine receptor-related mRNAs (DRD1, DRD2, DRD3 and D3nf) at two time points during a sensitizing-regimen of nicotine and 2) whether DRD3 antagonism either during the initial treatment (induction) or at a later challenge exposure (expression) is able to block nicotine sensitization. Nicotine-induced changes were seen for DRD3 and D3nf mRNAs in the nucleus accumbens shell early in repeated exposure in both age groups. D...
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography, Jan 21, 2015
Cardiac disease is a major cause of death in patients with muscular dystrophies. The use of feasi... more Cardiac disease is a major cause of death in patients with muscular dystrophies. The use of feasible and reproducible echocardiographic measures of cardiac function is critical to advance the field of therapeutics for dystrophic cardiomyopathy. Participants aged 8 to 18 years with genetically confirmed Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, or limb-girdle muscular dystrophy were enrolled at five centers, and standardized echocardiographic examinations were performed. Measures of systolic and diastolic function and speckle-tracking echocardiography-derived cardiac strain were reviewed independently by two central readers. Furthermore, echocardiographic measures from participants with DMD were compared with those from retrospective age-matched control subjects from a single site to assess measures of myocardial function. Forty-eight participants (mean age, 13.3 ± 2.7 years) were enrolled. Shortening fraction had a greater interobserver correlation (intraclass co...
Lancet, Jan 20, 2015
Cardiorespiratory failure is the leading cause of death in Duchenne muscular dystrophy. Based on ... more Cardiorespiratory failure is the leading cause of death in Duchenne muscular dystrophy. Based on preclinical and phase 2 evidence, we assessed the efficacy and safety of idebenone in young patients with Duchenne muscular dystrophy who were not taking concomitant glucocorticoids. In a multicentre phase 3 trial in Belgium, Germany, the Netherlands, Switzerland, France, Sweden, Austria, Italy, Spain, and the USA, patients (age 10-18 years old) with Duchenne muscular dystrophy were randomly assigned in a one-to-one ratio with a central interactive web response system with a permuted block design with four patients per block to receive idebenone (300 mg three times a day) or matching placebo orally for 52 weeks. Study personnel and patients were masked to treatment assignment. The primary endpoint was change in peak expiratory flow (PEF) as percentage predicted (PEF%p) from baseline to week 52, measured with spirometry. Analysis was by intention to treat (ITT) and a modified ITT (mITT), ...
Vision research, 1999
Although color-opponent neurons appear to subserve color vision, precisely how these cells encode... more Although color-opponent neurons appear to subserve color vision, precisely how these cells encode hue is still not clear. Single-unit, extracellular recordings from the rainbow trout optic tectum were made in order to examine the possible role of action potential timing in coding chromatic stimuli. We found that color-opponent units can exhibit differences in response latency which are a function of wavelength and response sign, with the OFF response exhibiting the shorter response latency. We also found that units often responded with spike bursts characterized by early and late spikes separated by a silent period, with the relative proportion of early and late spikes varying as a function of wavelength. This type of discharge pattern appears to be a result of inhibitory, color-opponent processes. We suggest that complete inhibition of early spikes may be the mechanism underlying the observed latency differences. These findings suggest a role for action potential patterning in codi...
Brain structure & function, Jan 26, 2014
Chronic nicotine exposure during adolescence induces dendritic remodeling of medium spiny neurons... more Chronic nicotine exposure during adolescence induces dendritic remodeling of medium spiny neurons (MSNs) in the nucleus accumbens (NAcc) shell. While nicotine-induced dendritic remodeling has frequently been described as persistent, the trajectory of dendrite remodeling is unknown. Specifically, no study to date has characterized the structural plasticity of dendrites in the NAcc immediately following chronic nicotine, leaving open the possibility that dendrite remodeling emerges gradually over time. Further, the neuropharmacological mechanisms through which nicotine induces dendrite remodeling are not well understood. To address these questions, rats were co-administered chronic nicotine (0.5 mg/kg) and the D1-dopamine receptor (D1DR) antagonist SCH-23390 (0.05 mg/kg) subcutaneously every other day during adolescence. Brains were then processed for Golgi-Cox staining either 1 day or 21 days following drug exposure and dendrites from MSNs in the NAcc shell digitally reconstructed in...
The journal of spinal cord medicine, 2007
To compare body composition in patients aged 11 to 21 years with spinal dysfunction due to spinal... more To compare body composition in patients aged 11 to 21 years with spinal dysfunction due to spinal cord injury (SCI) and spina bifida (SB) vs. able-bodied control (CTRL) and able-bodied overweight (OW) groups and to examine the relationships between resting energy expenditure (REE) and total lean mass (TLM) in the SCI, SB, CTRL, and OW groups. Two hundred fifteen subjects, including 85 CTRL, 31 OW, 33 SCI, and 66 SB, were evaluated. Body composition was estimated by dual energy x-ray absorptiometry (DXA). Measurements included height, weight, total lean mass (TLM), fat tissue mass (FTM), body mass index (BMI), BMI percentile (BMI%tile), and % fat. Resting energy measurements were obtained in fasting subjects with an open-circuit indirect calorimeter. There were gender differences in height, weight, BMI, TLM, fat mass, % fat, and REE. The REE in the SCI and SB groups was significantly different from that in the CTRL and OW groups, but no significant difference was found between the SC...
American journal of physical medicine & rehabilitation / Association of Academic Physiatrists
Fifteen subjects with Becker's muscular dystrophy (BMD) were studied prospectively over a 10-... more Fifteen subjects with Becker's muscular dystrophy (BMD) were studied prospectively over a 10-yr period to provide a profile of impairment and disability. Proximal lower extremity musculature (particularly the hip and knee extensors), ankle dorsiflexors, and neck flexors showed significantly early weakness. Extensor muscle groups were weaker than flexor muscles at the elbow and knee. The mean manual muscle test (MMT) strength grade for all muscle groups combined was 3.7 +/- 0.8 MMT units. There was a slowly progressive decline in strength, only -0.31 MMT units per decade, and the decline was relatively equal in all muscle groups. There was not side dominance. Severe contractures did not appear to be a problem until after transition to a wheelchair, and scoliosis was rare. Restrictive lung disease occurred as a late complication in a small percentage of cases; however, maximal expiratory pressure was significantly reduced early in the disease. Only two individuals (19%) had severe...
American journal of physical medicine & rehabilitation / Association of Academic Physiatrists
One hundred and sixty-two patients with Duchenne muscular dystrophy (DMD) were followed over a 10... more One hundred and sixty-two patients with Duchenne muscular dystrophy (DMD) were followed over a 10-yr period to provide a profile of impairment and disability. The median height and weight of DMD boys were normally distributed before ages 9-10, but during the second decade height was markedly reduced, and weight was no longer normally distributed. Younger boys gained more weight than normals, whereas older individuals actually showed weight loss. Manual muscle test (MMT) measurements showed loss of strength in a fairly linear fashion from ages 5-13 yr, -0.25 MMT units per year. Upper extremity muscles were stronger than lower extremity muscles, proximal muscle groups were weaker than distal muscle groups, and extensor muscles were weaker than flexor muscles. There was no side dominance. There was a change in the rate of strength loss at 14-15 yr, and the decline slowed to only -0.06 MMT units per year. Although MMT and quantitative strength measurement profiles were similar, the latt...
American journal of physical medicine & rehabilitation / Association of Academic Physiatrists
Data were collected prospectively for an impairment and disability profile for 86 hereditary moto... more Data were collected prospectively for an impairment and disability profile for 86 hereditary motor and sensory neuropathy, types I and II (HMSN) subjects over a 10-yr period. Our data confirm that HMSN is a slowly progressive disorder that has a very heterogeneous phenotypical expression. The disorder was characterized primarily by diffuse muscle weakness with prominent distal atrophy. The mean manual muscle test (MMT) strength grade for all muscle groups combined was 3.9 +/- 0.7 MMT units. There was a slowly progressive decline in strength, only -0.15 MMT units per decade. Distal muscle groups were weaker than proximal muscles, and the decline in strength of the ankle muscles was greater than for the proximal muscles. There was no side dominance. Anthropometric data revealed that distal atrophy may be masked by subcutaneous fat in female subjects. On average, HMSN subjects produced 20-40% less force than normal controls, using quantitative isometric and isokinetic strength measures...