John L Bradshaw

Monash University (Australia), Melbourne, Victoria, Australia

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Publications (367)1500.82 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent studies in young adult females with the fragile X mental retardation 1 (FMR1) gene premutation (PM) have shown subtle but significant impairments in executive control and postural stability. Less is known about the influence of age and FMR1 gene expression on executive control and postural stability in females with the PM. Here, we examined the attentional demands of reactive stepping using a well-validated measure of choice stepping reaction time under dual-task interference. We explored the interrelationships between step initiation times during a concurrent verbal fluency task and specific impairments in executive control previously reported in females with the PM. Our results showed increased dual-task interference on step initiation times and variability in female PM compared with control subjects. In addition, we observed greater choice stepping reaction time dual-task costs above the breakpoint of 81 CGG repeats relative to below this CGG range. Dual-task interference on both reaction time and movement time were significantly predicted by low working memory capacity in female PM carriers. Importantly, we revealed that FMR1 messenger RNA level is the most significant predictor accounting for dual-task stepping variability in both reaction time and movement time in PM females. These findings for the first time provide evidence linking elevated FMR1 messenger RNA levels that have been previously associated with FMR1 RNA toxicity and deficits in cerebellar motor and cognitive networks in a subgroup of at-risk PM women. Copyright © 2014 Elsevier Inc. All rights reserved.
    Neurobiology of Aging 11/2014; · 4.85 Impact Factor
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    ABSTRACT: This study aimed to (1) determine preliminary validity of the Developmental Behaviour Checklist-Hyperactivity Index (DBC-HI) as a screening measure of combined-type ADHD in autism and ADHD, and (2) compare emotional-behavioural disturbance using the DBC in autism, ADHD and autism + ADHD. Forty-nine age- and PIQ-matched young people [6–18 years; 12 autism, 13 ADHD, 12 autism + ADHD, 12 typically developing] were recruited. Parents completed the Conners-Revised Rating Scale and DBC. The DBC-HI displayed strong internal consistency and good external validity, reliably measuring combined-type ADHD. The DBC-HI distinguished autism from autism + ADHD with fair sensitivity and specificity. Individuals with autism + ADHD exhibited a more severe profile of emotional-behavioural disturbance than autism or ADHD alone. The DBC may be a useful ‘all-in-one’ screening tool to (1) identify comorbidity and (2) determine the severity of emotional-behavioural disturbance in autism and/or ADHD.
    Research in Autism Spectrum Disorders 09/2014; 8(9):1008–1015. · 2.96 Impact Factor
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    ABSTRACT: We sought to quantify subtle changes in motor control in multiple sclerosis (MS) using a Fitts law reciprocal aiming task presented on a computer touchscreen.
    Cognitive and behavioral neurology: official journal of the Society for Behavioral and Cognitive Neurology 09/2014; 27(3):139-47. · 1.09 Impact Factor
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    Addiction 07/2014; 109(7):1139-40. · 4.60 Impact Factor
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    ABSTRACT: This study aimed to compare the gait of children with ADHD - Combined Type (ADHD-CT) to typically developing (TD) children. Children with ADHD-CT (n=14; mean age 10 years 4 months) and a TD group (n=13; mean age 10 years 9 months) walked at self-selected slow, preferred and fast speed on an electronic walkway system. Participants completed a total of 15 walking trials; 5 trials per walking condition. Groups were matched on age, intellectual functioning, height and weight. In the preferred walking condition, there was no difference in spatio-temporal gait variables between the ADHD-CT and TD control groups. At self-selected fast speed, children with ADHD-CT were faster and walked with a higher cadence. The subtle alterations in gait pattern that may reflect a timing deficit is consistent with previous ADHD motor studies. In addition, this study extends previous studies in characterising the unique gait profile of non-medicated children with ADHD-CT where a diagnosis of autism spectrum disorder has been ruled out.
    Psychiatry Research 05/2014; · 2.68 Impact Factor
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    ABSTRACT: Recent studies report a higher risk of dementia and motor symptoms in females with the fragile X mental retardation 1 premutation (PM-carriers) than has hitherto been appreciated. Here, we use dual-task gait paradigms to identify potential markers of cognitive and motor decline in female PM-carriers. Spatiotemporal gait characteristics and variability of gait were assessed during single- and dual-task conditions in 28 female PM-carriers (mean age 41.32 ± 8.03 years) and 31 female controls with normal fragile X mental retardation 1 alleles (mean age 41.61 ± 8.30 years). Despite comparable gait characteristics at baseline, gait performance was significantly poorer for PM-carriers when performing concurrent working memory tasks (counting backwards by 3's or 7's) when compared with controls. Correlational analyses showed that low working memory capacity was significantly associated with dual-task interference for the gait domains of pace (speed, step length) and variability (step time, swing time) in PM-carriers. Multiple regression analyses further showed that the interaction between age and CGG repeat length was strongly predictive of gait variability during dual-task performance. These findings indicate for the first time that vulnerability in specific domains of gait control may act as sensitive surrogate markers of future decline in female PM-carriers.
    Neurobiology of aging 03/2014; · 5.94 Impact Factor
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    ABSTRACT: This study examines implicit sequence learning impairments that may indicate at-risk cerebellar profiles proposed to underlie some aspects of subtle cognitive and affective dysfunctions found amongst female FMR1 premutation carriers (PM-carriers). A total of 34 female PM-carriers and 33 age- and intelligence-matched controls completed an implicit symbolically primed serial reaction time task (SRTT) previously shown to be sensitive to cerebellar involvement. Implicit learning scores indicated a preservation of learning in both groups; however, PM-carriers demonstrated poorer learning through significantly elevated response latencies overall and at each specific block within the symbolic SRTT. Group comparisons also revealed a core deficit in response inhibition, alongside elevated inattentive symptoms in female PM-carriers. Finally, strong and significant associations were observed between poor symbolic SRTT performance and executive, visuospatial and affective deficits in the PM-carrier group. These associations remained strong even after controlling motor speed, and were not observed in age- and IQ-matched participants. The findings implicate cerebellar non-motor networks subserving the implicit sequencing of responses in cognitive-affective phenotypes previously observed in female PM-carriers. We contend that symbolic SRTT performance may offer clinical utility in future pharmaceutical interventions in female PM-carriers.
    Genes Brain and Behavior 02/2014; · 3.60 Impact Factor
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    ABSTRACT: Impulsivity is considered a core feature of problem gambling; however, self-reported impulsivity and inhibitory control may reflect disparate constructs. We examined self-reported impulsivity and inhibitory control in 39 treatment-seeking problem gamblers and 41 matched controls using a range of self-report questionnaires and laboratory inhibitory control tasks. We also investigated differences between treatment-seeking problem gamblers who prefer strategic (e.g., sports betting) and nonstrategic (e.g., electronic gaming machines) gambling activities. Treatment-seeking problem gamblers demonstrated elevated self-reported impulsivity, more go errors on the Stop Signal Task, and a lower gap score on the Random Number Generation task than matched controls. However, overall we did not find strong evidence that treatment-seeking problem gamblers are more impulsive on laboratory inhibitory control measures. Furthermore, strategic and nonstrategic problem gamblers did not differ from their respective controls on either self-reported impulsivity questionnaires or laboratory inhibitory control measures. Contrary to expectations, our results suggest that inhibitory dyscontrol may not be a key component for some treatment-seeking problem gamblers.
    Journal of Clinical and Experimental Neuropsychology 01/2014; · 2.16 Impact Factor
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    ABSTRACT: To analyse problem gamblers' decision making under conditions of risk and ambiguity, investigated underlying psychological factors associated with their choice behaviour and examine whether decision making differed in strategic (e.g., sports betting) and non-strategic (e.g., electronic gaming machine) problem gamblers. Cross-sectional study. Out-patient treatment centres and university testing facilities in Victoria, Australia. 39 problem gamblers and 41 age-, gender- and estimated-IQ-matched controls. Decision making tasks included the Iowa Gambling Task (IGT) and a Loss Aversion Task. The Prospect Valence Learning (PVL) model was used to provide an explanation of cognitive, motivational and response style factors involved in IGT performance. Overall, problem gamblers performed more poorly than controls on both the IGT (p = 0.04) and the Loss Aversion Task (p = 0.01), and their IGT decisions were associated with heightened attention to gains (p = 0.003) and less consistency (p = 0.002). Strategic problem gamblers did not differ from matched controls on either decision making task, but non-strategic problem gamblers performed worse on both the IGT (p = 0.006) and the Loss Aversion task (p = 0.02). Furthermore, we found differences in the PVL model parameters underlying strategic and non-strategic problem gamblers' choices on the IGT. Problem gamblers demonstrated poor decision making under conditions of risk and ambiguity. Strategic (e.g., sports betting, poker) and non-strategic (e.g., electronic gaming machines) problem gamblers differed in decision making and the underlying psychological processes associated with their decisions.
    Addiction 01/2014; · 4.60 Impact Factor
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    ABSTRACT: There is evidence which demonstrates that a subset of males with a premutation CGG repeat expansion (between 55 and 200 repeats) of the fragile X mental retardation 1 gene exhibit subtle deficits of executive function that progressively deteriorate with increasing age and CGG repeat length. However, it remains unclear whether similar deficits, which may indicate the onset of more severe degeneration, are evident in female PM-carriers. In the present study we explore whether female PM-carriers exhibit deficits of executive function which parallel those of male PM-carriers. Fourteen female fragile X premutation carriers without fragile X-associated tremor/ataxia syndrome and fourteen age, sex, and IQ matched controls underwent ocular motor and neuropsychological tests of select executive processes, specifically of response inhibition and working memory. Group comparisons revealed poorer inhibitory control for female premutation carriers on ocular motor tasks, in addition to demonstrating some difficulties in behaviour self-regulation, when compared to controls. A negative correlation between CGG repeat length and antisaccade error rates for premutation carriers was also found. Our preliminary findings indicate that impaired inhibitory control may represent a phenotype characteristic which may be a sensitive risk biomarker within this female fragile X premutation population.
    Brain and Cognition 01/2014; 85C:201-208. · 2.82 Impact Factor
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    ABSTRACT: Alcohol dependence, a chronic relapsing disorder, is characterized by an impaired ability to regulate compulsive urges to consume alcohol. Very few empirical studies have examined the presence of these executive deficits, how they relate to craving, and the enduring nature of these deficits during abstinence. As such, the current study aimed to characterize these cognitive deficits within a sample of 24 alcohol-dependent participants post-detoxification and 23 non-alcohol-dependent participants. Participants were administered the Sustained Attention to Response Task to measure response inhibition and sustained attention and the Random Number Generation Task to examine executive deficits. Correlations between cognitive performance and clinical measures of alcohol dependence were examined. As predicted, the alcohol-dependent group exhibited poorer performance across the domains of response inhibition, executive function, and attentional control. Cognitive performance was related to clinical measures of craving and years of alcohol consumption, whereas the duration of abstinence was not associated with improved cognitive performance. These findings highlight the need for therapeutic strategies to target these enduring neurocognitive deficits in improving the treatment of alcohol dependence.
    Archives of Clinical Neuropsychology 12/2013; · 2.00 Impact Factor
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    ABSTRACT: Fragile X Mental Retardation 1 (FMR1) premutation carriers (PM-carriers) have a defective trinucleotide expansion on the FMR1 gene that is associated with continuum of neuropsychological and mental disorders. Currently, little is known about the distinct subcomponents of executive function potentially impaired in female PM-carriers, and there have been no investigations into associations between executive function and incidences of mental disorders. A total of 35 female PM-carriers confirmed by Asuragen triple primed PCR DNA testing and 35 age- and intelligence-matched controls completed tests of executive function (i.e., response inhibition and working memory) and self-reported on social anxiety, depression, and ADHD predominantly inattentive (ADHD-PI) symptoms. Compared to controls, PM-carriers were significantly elevated on self-reported social anxiety and ADHD-PI symptoms. Irrespective of mental symptoms, female PM-carries performed significantly worse than controls on a response inhibition test, and further investigations revealed significant correlations between executive function performance and self-reported symptoms of anxiety, depression and ADHD-PI. Critically, among PM-carriers with good executive function performance, no women exceeded threshold markers for probable caseness of mental disorder. However, rates of probable caseness were elevated in those with average performance (response inhibition: social anxiety: 41.7%; depression: 20%; ADHD: 44.4%; working memory: social anxiety: 27.3%; depression: 9.1%; ADHD: 18.2%) and highly elevated for those with poor executive function performance (response inhibition: social anxiety: 58.3%; depression: 80%; ADHD: 55.6%; working memory: social anxiety: 100%; depression: 50%; ADHD: 83.3%). These data suggest that subtle executive dysfunction may be a useful neuropsychological indicator for a range of mental disorders previously reported in female PM-carriers. © 2013 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 10/2013; · 3.27 Impact Factor
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    ABSTRACT: Atrophy of the dentate nucleus is one of the major neuropathological changes in Friedreich ataxia (FRDA). Neuroimaging studies demonstrated white matter (WM) degeneration in FRDA. In this study, we used advanced tractography techniques to quantitatively measure WM changes in the dentato-thalamic and dentato-rubral tracts, and correlated these changes with cognitive profiles of FRDA. We also analysed diffusivity changes of the thalamo-cortical tract to assess whether neurological degeneration of WM extends beyond the primary site of involvement in FRDA. Twelve genetically proven individuals with FRDA and 14 controls were recruited. Sixty directions diffusion tensor images were acquired. The WM bundles from the dentate nucleus were estimated using a constrained spherical deconvolution method and the diffusivity characteristics measured. The Simon task was used to assess cognitive profile of FRDA. The dentato-rubral, dentato-thalamic and thalamo-cortical tracts manifested significantly lower fractional anisotropy, higher mean diffusivity and increased radial diffusivity in FRDA compared with controls. There was no difference in axial diffusivity between the two groups. The mean and radial diffusivity of the dentato-rubral tract was positively correlated with choice reaction time, congruent reaction time, incongruent reaction time and Simon effect reaction time and negatively with the larger GAA repeat. Significant changes in diffusivity characteristics were observed in the dentato-thalamic and thalamo-cortical tracts, suggesting extensive WM degeneration and affected WM structures in FRDA. Correlation of WM changes in the dentato-rubral tract with the cognitive assessment suggested that this tract is an important contributor to cognitive disturbances in FRDA.
    The Cerebellum 10/2013; · 2.60 Impact Factor
  • Clinical Neurophysiology 10/2013; 124(10):e69. · 2.98 Impact Factor
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    ABSTRACT: Recent investigations report a higher risk of motor symptoms in females with the FMR1 premutation (PM-carriers) than has hitherto been appreciated. Here we examined basic sensorimotor and postural control under different sensory and attentional dual-task demands. Physiological performance and postural sway measures from the Physiological Profile Assessment (Lord et al., 2003) were conducted in 28 female PM-carriers (mean age: 41.32±8.03) and 31 female controls with normal FMR1 alleles (mean age: 41.61±8.3). Multiple regression analyses was conducted to examine the moderating role of CGG-repeat length on the relation between age and postural sway under dual-task interference. In female PM-carriers, our results showed significantly poorer proprioceptive awareness, slower reaction time, and greater postural displacement when performing a concurrent verbal fluency task. Significantly, these findings showed age- and genetically-modulated changes in dual-task postural displacement in the medio-lateral direction in female PM-carriers. These findings highlight the sensitivity of postural control paradigms in identifying early cerebellar postural changes that may act as surrogate markers of future decline in female PM-carriers.
    Behavioural brain research 07/2013; · 3.22 Impact Factor
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    ABSTRACT: Motor overflow is overt involuntary movement that accompanies voluntary movement. This study investigated the change in overflow production across a timed trial and the factors that affected this profile. Seventeen children (aged 8-11 years), 17 young adults (aged 18-35 years), and 17 older adults (aged 60-80 years) performed a 5-s finger pressing task by exerting 33% or 66% of their maximal force output using either index finger. Overflow was recorded as force from the alternative index finger. Young adult overflow remained stable over the 5 s. The rate of overflow increase over time was significantly greater for children than young adults. There was also a tendency for a greater overflow increase in older adults than in young adults. This overflow gradient was also greater in the right hand, particularly for children. These findings indicate that the neurological processes underlying overflow production are age dependent. Overflow progressed in a dynamic fashion over the course of a trial in children and older adults, probably because of increased bilateral cortical activation and the facilitation of motor task performance. This study is unique in quantitatively capturing the dynamic profile of overflow production in healthy participants across the life span.
    The American Journal of Psychology 05/2013; 126(2):227-34. · 1.09 Impact Factor
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    ABSTRACT: Brain pathology in Friedreich ataxia is characterized by progressive degeneration of nervous tissue in the brainstem, cerebellum and cerebellar peduncles. Evidence of cerebral involvement is however equivocal. This brain imaging study investigates cerebello-cerebral white matter connectivity in Friedreich ataxia with diffusion MRI and tractography performed in 13 individuals homozygous for a GAA expansion in intron one of the frataxin gene and 14 age- and gender-matched control participants. New evidence is presented for disrupted cerebello-cerebral connectivity in the disease, leading to secondary effects in distant cortical and subcortical regions. Remote regions affected by primary cerebellar and brainstem pathology include the supplementary motor area, cingulate cortex, frontal cortices, putamen and other subcortical nuclei. The connectivity disruptions identified provide an explanation for some of the non-ataxic symptoms observed in the disease and support the notion of reverse cerebellar diaschisis. This is the first study to comprehensively map white matter connectivity disruptions in Friedreich ataxia using tractography, connectomic techniques and super-resolution track density imaging.
    Brain Structure and Function 04/2013; · 7.84 Impact Factor
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    ABSTRACT: For years, premutation-carriers of fragile X-syndrome (FXS) were assumed free from any deleterious phenotype. In this review, we discuss the current literature on neurocognitive, emotional and neuromotor profiles emerging in females with the fragile-X premutation, and discuss phenotypic profiles in male premutation-carriers to gain insights into possible underlying mechanisms associated with FMR1 gene expression. We contend that this emerging phenotypic profile in females with the fragile-X premutation needs further investigation using experimentally-driven tasks sensitive to neural networks especially vulnerable to FMR1 gene expression. Further investigation of developmental aspects of the female carrier profile is needed to determine the extent to which emotional, cognitive and neurobehavioral challenges indicate at-risk profiles for later degenerative decline, or rather a stable developmental phenotype. These future research avenues will provide critical new information which will enable identification of women at greatest risk for subtle age-dependent neurobehavioral changes well before the onset of more serious clinical consequences alongside the identification of biomarkers which may be useful in establishing the efficacy of future therapeutic interventions.
    Neuroscience & Biobehavioral Reviews 01/2013; · 10.28 Impact Factor
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    ABSTRACT: The mirror neuron hypothesis of autism is highly controversial, in part because there are conflicting reports as to whether putative indices of mirror system activity are actually deficient in autism spectrum disorder (ASD). Recent evidence suggests that a typical putative mirror system response may be seen in people with an ASD when there is a degree of social relevance to the visual stimuli used to elicit that response. Individuals with ASD (n = 32) and matched neurotypical controls (n = 32) completed a transcranial magnetic stimulation (TMS) experiment in which the left primary motor cortex (M1) was stimulated during the observation of static hands, individual (i.e., one person) hand actions, and interactive (i.e., two person) hand actions. Motor-evoked potentials (MEP) were recorded from the contralateral first dorsal interosseous, and used to generate an index of interpersonal motor resonance (IMR; a putative measure of mirror system activity) during action observation. There was no difference between ASD and NT groups in the level of IMR during the observation of these actions. These findings provide evidence against a global mirror system deficit in ASD, and this evidence appears to extend beyond stimuli that have social relevance. Attentional and visual processing influences may be important for understanding the apparent role of IMR in the pathophysiology of ASD.
    Frontiers in Human Neuroscience 01/2013; 7:218. · 2.90 Impact Factor

Publication Stats

8k Citations
1,500.82 Total Impact Points


  • 1969–2014
    • Monash University (Australia)
      • • School of Psychology and Psychiatry
      • • Centre for Developmental Psychiatry and Psychology
      Melbourne, Victoria, Australia
  • 2013
    • Victoria University Sydney
      Sydney, New South Wales, Australia
  • 1994–2013
    • University of Melbourne
      • • Florey Institute of Neuroscience and Mental Health
      • • Melbourne School of Psychological Sciences
      • • Department of Paediatrics
      • • Department of Psychiatry
      Melbourne, Victoria, Australia
  • 2008–2012
    • Monash University (Malaysia)
      Labuan, Labuan, Malaysia
    • University of Western Australia
      • School of Psychology
      Perth, Western Australia, Australia
    • University of Reading
      • Department of Psychology
      Reading, ENG, United Kingdom
  • 2010–2011
    • Flinders University
      • School of Psychology
      Adelaide, South Australia, Australia
  • 2009
    • University of Queensland 
      • School of Psychology
      Brisbane, Queensland, Australia
    • Murdoch Childrens Research Institute
      Melbourne, Victoria, Australia
  • 2005
    • Deakin University
      • School of Psychology
      Geelong, Victoria, Australia
  • 2004
    • University of Auckland
      • Department of Sport and Exercise Science
      Auckland, Auckland, New Zealand
  • 2002
    • University of Wales
      • Department of Psychology
      Cardiff, Wales, United Kingdom
    • University of Vic
      • Department of Psychology
      Vic, Catalonia, Spain
  • 2001
    • Victoria University Melbourne
      Melbourne, Victoria, Australia
  • 1992
    • Clayton State University
      Georgia, United States
  • 1977
    • Massachusetts Institute of Technology
      Cambridge, Massachusetts, United States
  • 1971
    • McGill University
      Montréal, Quebec, Canada