Hosking J.G.,Harvard University |
Kastman E.K.,Harvard University |
Dorfman H.M.,Harvard University |
Samanez-Larkin G.R.,Duke University |
And 4 more authors.
Neuron | Year: 2017
Psychopathy is a personality disorder with strong links to criminal behavior. While research on psychopathy has focused largely on socio-affective dysfunction, recent data suggest that aberrant decision making may also play an important role. Yet, the circuit-level mechanisms underlying maladaptive decision making in psychopathy remain unclear. Here, we used a multi-modality functional imaging approach to identify these mechanisms in a population of adult male incarcerated offenders. Psychopathy was associated with stronger subjective value-related activity within the nucleus accumbens (NAcc) during inter-temporal choice and with weaker intrinsic functional connectivity between NAcc and ventromedial prefrontal cortex (vmPFC). NAcc-vmPFC connectivity strength was negatively correlated with NAcc subjective value-related activity; however, this putative regulatory pattern was abolished as psychopathy severity increased. Finally, weaker cortico-striatal regulation predicted more frequent criminal convictions. These data suggest that cortico-striatal circuit dysregulation drives maladaptive decision making in psychopathy, supporting the notion that reward system dysfunction comprises an important neurobiological risk factor. Copyright © 2017 Elsevier Inc. All rights reserved.
Bales K.L.,University of California at Davis |
Bales K.L.,California National Primate Research Center |
Perkeybile A.M.,University of California at Davis |
Conley O.G.,University of California at Davis |
And 7 more authors.
Biological Psychiatry | Year: 2013
Background: Oxytocin (OT) is a hormone shown to be involved in social bonding in animal models. Intranasal OT is currently in clinical trials for use in disorders such as autism and schizophrenia. We examined long-term effects of intranasal OT given developmentally in the prairie vole (Microtus ochrogaster), a socially monogamous rodent, often used as an animal model to screen drugs that have therapeutic potential for social disorders. Methods: We treated voles with one of three dosages of intranasal OT, or saline, from day 21 (weaning) through day 42 (sexual maturity). We examined both social behavior immediately following administration, as well as long-term changes in social and anxiety behavior after treatment ceased. Group sizes varied from 8 to 15 voles (n = 89 voles total). Results: Treatment with OT resulted in acute increases in social behavior in male voles with familiar partners, as seen in humans. However, long-term developmental treatment with low doses of intranasal OT resulted in a deficit in partner preference behavior (a reduction of contact with a familiar opposite-sex partner, used to index pair-bond formation) by male voles. Conclusions: Long-term developmental treatment with OT may show results different to those predicted by short-term studies, as well as significant sex differences and dosage effects. Further animal study is crucial to determining safe and effective strategies for use of chronic intranasal OT, especially during development. © 2013 Society of Biological Psychiatry.
Solomon M.,University of California at Davis |
Solomon M.,MIND Institute |
McCauley J.B.,University of California at Davis |
McCauley J.B.,MIND Institute |
And 3 more authors.
Neuropsychologia | Year: 2016
Introduction: To further investigate manifestations of episodic memory impairments in adolescents, we examined the role of encoding on recognition of stimuli in conditions designed to emphasize their item-specific versus relational characteristics in a group of 12-18 year olds with autism spectrum disorders (ASD). We also examined how strategic learning and memory processes, verbal abilities, attention, and age were associated with recognition in this group. Materials and method: Twenty two high functioning adolescents with ASD (mean age=15 years; SD=1.8; range=12.2-17.9), and 26 age, gender, and IQ-matched adolescents with typical development (TYP) (mean age=14.7 years; SD=1.9; range=12.3-17.8) completed the Relational and Item-Specific Encoding task (RiSE), the California Verbal Learning Test-Children's Version (CVLT-C), the Wechsler Abbreviated Scales of Intelligence, and the Connors' Parent Rating Scale-Revised. Univariate statistical analyses were performed. Results: The ASD group showed poorer performance on strategic memory assessed by the CVLT-C. Surprisingly, on the RiSE, ASD showed poorer discriminability for objects encoded in item-specific versus relational encoding conditions and were more impaired in familiarity (after relational encoding) than in recollection. ASD also did not show the hypothesized association between item and associative recognition and CVLT-C performance found in TYP. Instead, in the ASD group recognition was associated with increased age. Conclusions: Findings from the RiSE task demonstrated that adolescents with ASD do not always exhibit impaired memory for relational information as commonly believed. Instead, memory was worse when cognitive control demands were high, when encoding focused on specific item features, and when familiarity was used to retrieve relational information. Recognition also was better in older participants. This suggests that learning and memory deficits in adolescents with ASD, may not be due primarily to failed relational binding processes in the hippocampus but, rather to disrupted strategic memory and familiarity processes associated with the prefrontal and perirhinal cortices. These findings demonstrate the importance and utility of using well-validated cognitive neuroscience tasks and of considering the ages of participants when comparing the neural underpinnings of different memory processes in both typical and atypical populations. © 2016 ElsevierLtd.
Anagnostou E.,Bloorview Research Institute |
Anagnostou E.,University of Toronto |
Hansen R.,MIND Institute |
Hansen R.,University of California at Davis
Current Opinion in Pediatrics | Year: 2011
PURPOSE OF REVIEW: Up to 35% of children and youth with autism spectrum disorder (ASD) receive at least one psychotropic medication. 50-70% of this population also receives biologically based complementary and alternative medicine (CAM). The data evaluating such practices are being reviewed. RECENT FINDINGS: There are accumulating data to suggest that atypical antipsychotics and stimulants may be useful for the treatment of irritability and hyperactivity in children and youth with ASD. The data for the use of selective serotonin reuptake inhibitors are less promising. New avenues of pharmacologic research targeting molecular targets identified by genomics, animal models and neuropathology are being evaluated. Areas of interest include glutamate/gamma-aminobutyric acid systems, neuropeptides such as oxytocin, and immune dysfunction, among others. In the case of biologically based CAM, a few compounds have been shown to be well tolerated, although efficacy is still being evaluated, such as melatonin, certain vitamins, and omega 3 fatty acids. Others have safety concerns without demonstrated efficacy, such as chelation therapies. SUMMARY: Accumulating data suggest a series of existing medications may be useful in ASD and large randomized clinical trials are necessary to evaluate safety and efficacy of both pharmaceuticals and alternative treatments. © 2011 Wolters Kluwer Health | Lippincott Williams &Wilkins.
Solomon M.,University of California at Davis |
Solomon M.,Mind Institute |
Yoon J.H.,University of California at Davis |
Ragland J.D.,University of California at Davis |
And 5 more authors.
Biological Psychiatry | Year: 2014
Background Autism spectrum disorders (ASDs) involve impairments in cognitive control. In typical development (TYP), neural systems underlying cognitive control undergo substantial maturation during adolescence. Development is delayed in adolescents with ASD. Little is known about the neural substrates of this delay. Methods We used event-related functional magnetic resonance imaging and a cognitive control task involving overcoming a prepotent response tendency to examine the development of cognitive control in young (ages 12-15; n = 13 with ASD and n = 13 with TYP) and older (ages 16-18; n = 14 with ASD and n = 14 with TYP) adolescents with whole-brain voxelwise univariate and task-related functional connectivity analyses. Results Older ASD and TYP showed reduced activation in sensory and premotor areas relative to younger ones. The older ASD group showed reduced left parietal activation relative to TYP. Functional connectivity analyses showed a significant age by group interaction with the older ASD group exhibiting increased functional connectivity strength between the ventrolateral prefrontal cortex and the anterior cingulate cortex, bilaterally. This functional connectivity strength was related to task performance in ASD, whereas that between dorsolateral prefrontal cortex and parietal cortex (Brodmann areas 9 and 40) was related to task performance in TYP. Conclusions Adolescents with ASD rely more on reactive cognitive control, involving last-minute conflict detection and control implementation by the anterior cingulate cortex and ventrolateral prefrontal cortex, versus proactive cognitive control requiring processing by dorsolateral prefrontal cortex and parietal cortex. Findings await replication in larger longitudinal studies that examine their functional consequences and amenability to intervention. © 2014 Society of Biological Psychiatry.
Lozano R.,MIND institute |
Lozano R.,University of California at Davis |
Hare E.B.,MIND institute |
Hare E.B.,University of California at Davis |
And 2 more authors.
Neuropsychiatric Disease and Treatment | Year: 2014
Fragile X syndrome (FXS) is the most common genetic cause of intellectual disability and the most common single-gene cause of autism. It is caused by mutations on the fragile X mental retardation gene (FMR1) and lack of fragile X mental retardation protein, which in turn, leads to decreased inhibition of translation of many synaptic proteins. The metabotropic glutamate receptor (mGluR) hypothesis states that the neurological defcits in individuals with FXS are due mainly to downstream consequences of overstimulation of the mGluR pathway. The main efforts have focused on mGluR5 targeted treatments; however, investigation on the gamma-aminobutyric acid (GABA) system and its potential as a targeted treatment is less emphasized. The fragile X mouse models (Fmr1-knock out) show decreased GABA subunit receptors, decreased synthesis of GABA, increased catabolism of GABA, and overall decreased GABAergic input in many regions of the brain. Consequences of the reduced GABAergic input in FXS include oversensitivity to sensory stimuli, seizures, and anxiety. Deficits in the GABA receptors in different regions of the brain are associated with behavioral and attentional processing deficits linked to anxiety and autistic behaviors. The understanding of the neurobiology of FXS has led to the development of targeted treatments for the core behavioral features of FXS, which include social deficits, inattention, and anxiety. These symptoms are also observed in individuals with autism and other neurodevelopmental disorders, therefore the targeted treatments for FXS are leading the way in the treatment of other neurodevelopmental syndromes and autism. The GABAergic system in FXS represents a target for new treatments. Herein, we discuss the animal and human trials of GABAergic treatment in FXS. Arbaclofen and ganaxolone have been used in individuals with FXS. Other potential GABAergic treatments, such as riluzole, gaboxadol, tiagabine, and vigabatrin, will be also discussed. Further studies are needed to determine the safety and efficacy of GABAergic treatments for FXS. © 2014 Lozano et al.
Jabes A.,University of Fribourg |
Lavenex P.B.,University of Fribourg |
Amaral D.G.,Mind Institute |
Lavenex P.,University of Fribourg
European Journal of Neuroscience | Year: 2010
The dentate gyrus is one of only two regions of the mammalian brain where substantial neurogenesis occurs postnatally. However, detailed quantitative information about the postnatal structural maturation of the primate dentate gyrus is meager. We performed design-based, stereological studies of neuron number and size, and volume of the dentate gyrus layers in rhesus macaque monkeys (Macaca mulatta) of different postnatal ages. We found that about 40% of the total number of granule cells observed in mature 5-10-year-old macaque monkeys are added to the granule cell layer postnatally; 25% of these neurons are added within the first three postnatal months. Accordingly, cell proliferation and neurogenesis within the dentate gyrus peak within the first 3 months after birth and remain at an intermediate level between 3 months and at least 1 year of age. Although granule cell bodies undergo their largest increase in size during the first year of life, cell size and the volume of the three layers of the dentate gyrus (i.e. the molecular, granule cell and polymorphic layers) continue to increase beyond 1 year of age. Moreover, the different layers of the dentate gyrus exhibit distinct volumetric changes during postnatal development. Finally, we observe significant levels of cell proliferation, neurogenesis and cell death in the context of an overall stable number of granule cells in mature 5-10-year-old monkeys. These data identify an extended developmental period during which neurogenesis might be modulated to significantly impact the structure and function of the dentate gyrus in adulthood. © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
News Article | April 22, 2016
The Simons Foundation Autism Research Initiative (SFARI) launched the Simons Foundation Powering Autism Research for Knowledge (SPARK) today, an online campaign that will lead to the largest autism study in the United States. SPARK is looking for 50,000 individuals diagnosed with autism. The online initiative will collect DNA as well as information from these individuals and their families. The good news is that you can participate! Findings from this study aim to better analyze the cause of autism as well as speed up the developments of new therapies, treatments and support systems that can help families living with the condition. To date, researchers have identified about 50 genes that are involved in autism. Scientists are also estimating that approximately 300 more genes play a role in its development. Through SPARK, experts aim to study the biological mechanisms involved in autism as well as the impacts of genetics' interaction with environmental factors. "Knowledge is power, and SPARK was created because we simply haven't learned enough about the genetics and other possible causes of autism," said Wendy Chung, SPARK's chief investigator and SFARI's clinical research director. "Together, we can 'spark' a movement in autism research." Under SPARK, there are several studies that interested parties can become involved in and this initiative will connect these participants to the researchers. SFARI partnered with 21 clinical sites affiliated by participating universities as well as various local and national autism organizations. The list of university-affiliated clinical sites includes the University of California, Davis MIND Institute, University of Minnesota and the University of North Carolina at Chapel Hill to name a few. Autism Science Foundation, Mid-Michigan Autism Association and Autism Society the Heartland are also part of the several partner organizations. These sites and groups are currently recruiting participants for this historical autism study. To join, interested parties can create an account on the SPARK website to kick off their journey. According to the U.S. Centers for Disease Control and Prevention (CDC), 1 in 68 American children have been diagnosed with autism spectrum disorder (ASD). About 1 in 42 boys are diagnosed with ASD compared to 1 in 189 among girls. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.
Srivastava S.,Mind Institute |
Buonocore M.H.,Mind Institute |
Buonocore M.H.,Imaging Research Center |
Simon T.J.,Mind Institute
Human Brain Mapping | Year: 2012
Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a neurogenetic disorder associated with neurocognitive impairments. This article focuses on the cortical gyrification changes that are associated with the genetic disorder in 6-15-year-old children with 22q11.2DS, when compared with a group of age-matched typically developing (TD) children. Local gyrification index (lGI; Schaer et al. : IEEE Trans Med Imaging 27:161-170) was used to characterize the cortical gyrification at each vertex of the pial surface. Vertex-wise statistical analysis of lGI differences between the two groups revealed cortical areas of significant reduction in cortical gyrification in children with 22q11.2DS, which were mainly distributed along the medial aspect of each hemisphere. To gain further insight into the developmental trajectory of the cortical gyrification, we examined age as a factor in lGI changes over the 6-15 years of development, within and across the two groups of children. Our primary results pertaining to the developmental trajectory of cortical gyrification revealed cortical regions where the change in lGI over the 6-15 years of age was significantly modulated by diagnosis, implying an atypical development of cortical gyrification in children with 22q11.2DS, when compared with the TD children. Significantly, these cortical areas included parietal structures that are associated, in typical individuals, with visuospatial, attentional, and numerical cognition tasks in which children with 22q11.2DS show impairments. © 2011 Wiley Periodicals, Inc.
News Article | November 22, 2016
To make the donation of toys and other gifts easier for generous businesses, non-profit organizations and individuals who would like to make the season brighter for hospitalized children, UC Davis Children's Hospital is offering donors the opportunity to drive up and drop off donations for the holidays. The holiday toy drive will be held at the circular driveway of the UC Davis MIND Institute, 2825 50th St., Sacramento. The drop-off opportunity will be held from Tuesday, Dec. 20 through Friday, Dec. 23 from 9:30 a.m. to 4:30 p.m. Donors dropping off donations will be greeted in the driveway. "We really appreciate all of our donors who make the holiday season brighter with their gifts," said Diana Sundberg, manager of the UC Davis Child Life and Creative Arts Therapy Department. "The kindness of donors will make an important difference in the lives of many families who have a sick child in the hospital this time of year." The gifts will be given to hospitalized children during the holidays and throughout the year to mark the end of treatment and for completing tests and other procedures. Toys and gifts also will be used in hospital playrooms and waiting areas throughout the year. Please note: Even slightly used toys cannot be accepted because of infection-control precautions. UC Davis Children's Hospital is the Sacramento region's only nationally ranked, comprehensive hospital providing care for infants, children, adolescents and young adults with primary, subspecialty and critical care. It includes the Central Valley's only pediatric emergency department and Level I pediatric trauma center, which offers the highest level of care for its critically ill patients, as well as the West Coast's only Level I children's surgery center. The 129-bed children's hospital includes the state-of-the-art 49-bed neonatal and 24-bed pediatric intensive care and pediatric cardiac intensive care units. For more information, visit children.ucdavis.edu.