Academy of Arts and science

Amsterdam, Netherlands

Academy of Arts and science

Amsterdam, Netherlands
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Bao A.-M.,Zhejiang University | Swaab D.F.,Academy of Arts and science
Frontiers in Neuroendocrinology | Year: 2011

During the intrauterine period a testosterone surge masculinizes the fetal brain, whereas the absence of such a surge results in a feminine brain. As sexual differentiation of the brain takes place at a much later stage in development than sexual differentiation of the genitals, these two processes can be influenced independently of each other. Sex differences in cognition, gender identity (an individual's perception of their own sexual identity), sexual orientation (heterosexuality, homosexuality or bisexuality), and the risks of developing neuropsychiatric disorders are programmed into our brain during early development. There is no evidence that one's postnatal social environment plays a crucial role in gender identity or sexual orientation. We discuss the relationships between structural and functional sex differences of various brain areas and the way they change along with any changes in the supply of sex hormones on the one hand and sex differences in behavior in health and disease on the other. © 2011 Elsevier Inc.

Figee M.,University of Amsterdam | Vink M.,University Utrecht | De Geus F.,University Utrecht | Vulink N.,University of Amsterdam | And 3 more authors.
Biological Psychiatry | Year: 2011

Background: Obsessive-compulsive disorder (OCD) is primarily conceived as an anxiety disorder but has features resembling addictive behavior. Patients with OCD may develop dependency upon compulsive behaviors because of the rewarding effects following reduction of obsession-induced anxiety. Reward processing is critically dependent on ventral striatal-orbitofrontal circuitry and brain imaging studies in OCD have consistently shown abnormal activation within this circuitry. This is the first functional imaging study to investigate explicitly reward circuitry in OCD. Methods: Brain activity during reward anticipation and receipt was compared between 18 OCD patients and 19 healthy control subjects, using a monetary incentive delay task and functional magnetic resonance imaging. Reward processing was compared between OCD patients with predominantly contamination fear and patients with predominantly high-risk assessment. Results: Obsessive-compulsive disorder patients showed attenuated reward anticipation activity in the nucleus accumbens compared with healthy control subjects. Reduced activity of the nucleus accumbens was more pronounced in OCD patients with contamination fear than in patients with high-risk assessment. Brain activity during reward receipt was similar between patients and control subjects. A hint toward more dysfunctional reward processing was found in treatment-resistant OCD patients who subsequently were successfully treated with deep brain stimulation of the nucleus accumbens. Conclusions: Obsessive-compulsive disorder patients may be less able to make beneficial choices because of altered nucleus accumbens activation when anticipating rewards. This finding supports the conceptualization of OCD as a disorder of reward processing and behavioral addiction. © 2011 Society of Biological Psychiatry.

Plooij B.,VU University Amsterdam | Swaab D.,Academy of Arts and science | Scherder E.,VU University Amsterdam
Reviews in the Neurosciences | Year: 2011

Increasing age and dementia are accompanied by an increased risk for undertreatment of pain owing to difficulty in assessing pain. Registration of autonomic responses to pain may contribute to a more reliable pain assessment. The aim of this review was to gain more insight into autonomic responses to pain in older persons with and without dementia. Literature searches were performed in the online databases MEDLINE and Web of Science. Seven studies on autonomic responses to pain in older people with or without dementia were included in the review. Autonomic responses to pain are present in older people with and without dementia, although they may be attenuated. Because no distinction could be made between different dementia subtypes based on these studies, predictions of changes in autonomic responses to pain have been made based on neuropathological changes. It can be concluded that autonomic responses to pain are attenuated in older people with and without dementia. Studies to specify the changes in the different autonomic responses for the different dementia subtypes are needed. © 2011 by Walter de Gruyter Berlin Boston.

Savic I.,Karolinska Institutet | Garcia-Falgueras A.,Academy of Arts and science | Garcia-Falgueras A.,Autonomous University of Barcelona | Swaab D.F.,Academy of Arts and science
Progress in Brain Research | Year: 2010

It is believed that during the intrauterine period the fetal brain develops in the male direction through a direct action of testosterone on the developing nerve cells, or in the female direction through the absence of this hormone surge. According to this concept, our gender identity (the conviction of belonging to the male or female gender) and sexual orientation should be programmed into our brain structures when we are still in the womb. However, since sexual differentiation of the genitals takes place in the first two months of pregnancy and sexual differentiation of the brain starts in the second half of pregnancy, these two processes can be influenced independently, which may result in transsexuality. This also means that in the event of ambiguous sex at birth, the degree of masculinization of the genitals may not reflect the degree of masculinization of the brain.There is no proof that social environment after birth has an effect on gender identity or sexual orientation. Data on genetic and hormone independent influence on gender identity are presently divergent and do not provide convincing information about the underlying etiology. To what extent fetal programming may determine sexual orientation is also a matter of discussion. A number of studies show patterns of sex atypical cerebral dimorphism in homosexual subjects. Although the crucial question, namely how such complex functions as sexual orientation and identity are processed in the brain remains unanswered, emerging data point at a key role of specific neuronal circuits involving the hypothalamus. © 2010 Elsevier B.V.

De Vries F.E.,VU University Amsterdam | De Wit S.J.,VU University Amsterdam | Cath D.C.,Altrecht Academic Anxiety Center | Cath D.C.,University Utrecht | And 8 more authors.
Biological Psychiatry | Year: 2014

Background: Subtle deficits in executive functioning are present in patients with obsessive-compulsive disorder (OCD) and their first-degree relatives, suggesting involvement of the frontoparietal circuits. The neural correlates of working memory may be a neurocognitive endophenotype of OCD.Methods: Forty-three unmedicated OCD patients, 17 unaffected siblings, and 37 matched comparison subjects performed a visuospatial n-back task, with a baseline condition (N0) and three working memory load levels (N1, N2, N3) during functional magnetic resonance imaging. Task-related brain activity was compared between groups in frontoparietal regions of interest. Generalized psychophysiological interaction analyses were used to study task-related changes in functional connectivity.Results: Obsessive-compulsive disorder patients, compared with comparison subjects and siblings, showed increased error rates at N3. Compared with comparison subjects, OCD patients showed task-related hyperactivation in left dorsal frontal areas and left precuneus associated with better task performance. Siblings exhibited hyperactivation in a bilateral frontoparietal network. Increased task load was associated with increased task-related brain activity, but in OCD patients and siblings this increase was smaller from load N2 to N3 than in comparison subjects. Obsessive-compulsive disorder patients, compared with siblings and comparison subjects, showed increased task-related functional connectivity between frontal regions and bilateral amygdala.Conclusions: These findings indicate that compensatory frontoparietal brain activity in OCD patients and their unaffected relatives preserves task performance at low task loads but is insufficient to maintain performance at high task loads. Frontoparietal dysfunction may constitute a neurocognitive endophenotype for OCD, possibly reflecting limbic interference with and neural inefficiency within the frontoparietal network. © 2014 Society of Biological Psychiatry.

Bao A.-M.,Zhejiang University | Swaab D.F.,Academy of Arts and science
Neuroscientist | Year: 2010

Sex differences in the brain are reflected in behavior and in the risk for neuropsychiatric disorders. The fetal brain develops in the male direction due to a direct effect of testosterone on the developing neurons, or in the female direction due to the absence of such a testosterone surge. Because sexual differentiation of the genitals takes place earlier in intrauterine life than sexual differentiation of the brain, these two processes can be influenced independently of each other. Gender identity (the conviction of belonging to the male or female gender), sexual orientation (heterosexuality, homosexuality, or bisexuality), pedophilia, sex differences in cognition, and the risks for neuropsychiatric disorders are programmed into our brains during early development. There is no proof that postnatal social environment has any crucial effect on gender identity or sexual orientation. Structural and functional sex differences in brain areas, together with changes in sex hormone levels and their receptors in development and adulthood, are closely related to sex differences in behavior and neuropsychiatric disorders. Knowing that such a relationship exists may help bring about sex-specific therapeutic strategies. © The Author(s) 2010.

Most E.I.S.,Academy of Arts and science | Aboudan S.,Academy of Arts and science | Aboudan S.,University of Florence | Scheltens P.,University Medical Center | And 2 more authors.
American Journal of Geriatric Psychiatry | Year: 2012

Objective: Sleep disturbances such as nocturnal awakenings frequently occur in demented elderly persons and can contribute to depression, cognitive impairment, and caregiver burden. Recognizing sleep disturbances at an early stage of the disease progress is a first prerequisite of intervention and monitoring of progress. This study aimed to investigate the reliability of subjective sleep reports in early-and moderate-stage Alzheimer dementia (AD), by investigating whether they differ from matched healthy normal comparison groups with respect to the discrepancy of subjective and objective sleep estimates. Measurements: Subjective sleep was assessed using the Pittsburgh Sleep Quality Index, the Sleep Disorders Questionnaire, and the Athens Insomnia Scale. Objective sleep was estimated using actigraphy. Results: As compared with the normal comparison group (N = 26), AD patients (N = 55) complained less of insomnia, while their objective sleep estimates indicated, in fact, more disturbed sleep, including a longer sleep onset latency and a lower sleep efficiency. Regression analyses aimed at predicting actigraphic sleep parameter estimates from their subjective counterparts showed significant predictive value of only very few subjective sleep parameters. Subjective reports of both patients and the normal comparison group had significant value in predicting actigraphic indices of total sleep time and bedtime. In addition, subjective reports of the normal comparison group, but not of patients, were of value to predict actigraphic indices of sleep onset latency, average sleep bout duration, and sleep efficiency. Conclusion: The results show that the value of sleep questionnaires is limited in early-and moderate-stage AD. Actigraphy may be essential to ensure that sleep problems do not go undetected and untreated. © 2012 American Association for Geriatric Psychiatry.

Bergfeld I.O.,University of Amsterdam | Mantione M.,University of Amsterdam | Hoogendoorn M.L.C.,University of Amsterdam | Denys D.,University of Amsterdam | Denys D.,Academy of Arts and science
Brain Stimulation | Year: 2013

Background: Deep brain stimulation (DBS) is routinely used as a treatment for treatment-refractory Parkinson's disease and has recently been proposed for psychiatric disorders such as Tourette syndrome (TS), obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). Although cognitive deterioration has repeatedly been shown in patients with Parkinson's disease following DBS, the impact of DBS on cognitive functioning in psychiatric patients has not yet been reviewed. Objective: Reviewing the available literature on cognitive functioning following DBS in psychiatric patients. Methods: A systematic literature search in PubMed, EMBASE and Web of Science, last updated in September 2012, found 1470 papers. Abstracts were scrutinized and 26 studies examining cognitive functioning of psychiatric patients following DBS were included on basis of predetermined inclusion criteria. Results: Twenty-six studies reported cognitive functioning of 130 psychiatric patients following DBS (37 TS patients, 56 OCD patients, 28 MDD patients, 6 patients with Alzheimer's disease, and 3 patients with other disorders). None of the studies reported substantial cognitive decline following DBS. On the contrary, 13 studies reported cognitive improvement following DBS. Conclusion: Preliminary results suggest that DBS in psychiatric disorders does not lead to cognitive decline. In selected cases cognitive functioning was improved following DBS. However, cognitive improvement cannot be conclusively attributed to DBS since studies are hampered by serious limitations. We discuss the outcomes in light of these limitations and offer suggestions for future work. © 2013 Elsevier Inc. All rights reserved.

Pooresmaeili A.,Academy of Arts and science | Poort J.,Academy of Arts and science | Thiele A.,Northumbria University | Roelfsema P.R.,Academy of Arts and science | Roelfsema P.R.,VU University Amsterdam
Journal of Neuroscience | Year: 2010

The visual system encodes the features of visual stimuli as well as their behavioral relevance. Stimuli with a high luminance contrast evoke more activity in the visual cortex than stimuli with a low contrast. At the same time, attended stimuli evoke more activity than nonattended stimuli. There is a debate about how visual features and attention jointly determine neuronal activity in the visual cortex. Some studies suggested that attention increases apparent contrast (Reynolds et al., 2000), others that attention amplifies responses by a constant factor (Williford and Maunsell, 2006), and yet others that attention and contrast have largely additive effects (Buracas and Boynton, 2007; Thiele et al., 2009). The influence of attention on contrast sensitivity differs between neurons, raising the possibility that attention and contrast could be coded conjointly in a population of neurons. Here we investigate this possibility by recording neuronal activity at multiple sites in the primary visual cortex of macaque monkeys using multielectrode recording techniques and support vector machines to decode attended stimuli as well as stimulus contrast. We find that many, but not all, V1 neurons are influenced by attention and that the effects of attention and contrast are additive on average. Stimulus contrast can be decoded from neuronal responses not strongly modulated by attention, whereas the attended stimulus can be decoded as the difference in activity of cells that are influenced by attention and cells that are not. The success of the approach suggests that visual attention and stimulus contrast are represented by largely separable codes. Copyright © 2010 the authors.

Korecka J.A.,Academy of Arts and science | Eggers R.,Academy of Arts and science | Swaab D.F.,Academy of Arts and science | Bossers K.,Academy of Arts and science | Verhaagen J.,Academy of Arts and science
Restorative Neurology and Neuroscience | Year: 2013

Purpose: Parkinson's disease (PD) is a movement disorder mainly characterized by progressive neurodegeneration of dopaminergic (DAergic) neurons in the substantia nigra (SN). As yet, unknown molecular changes contribute to the development of PD leading to a great need for in vivo models that herald this disorder. Here we characterize an animal model presenting early PD pathology. Methods: Young, adult C57/BL6 mice were treated for five weeks twice a week with 15 mg/kg 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP) in combination with 250 mg/kg probenecid. During the treatment mice were tested on their dopamine dependent movement skills. The integrity of their nigrostriatal system was examined through immunohistochemical studies. Results: During the treatment, mice developed dopamine-dependent movement deficits induced by loss of tyrosine hydroxylase (TH) positive nigrostriatal axon terminals. Immunohistochemical study identified astrogliosis and microgliosis in the SN but no decrease of TH immunostaining, demonstrating lack of DAergic neuron degeneration. We also observed formation of α-synuclein inclusion bodies in the SN. Conclusions: The combined features of this MPTP model appear to represent an early neurotoxic cellular stress to the SN neurons bearing a striking resemblance to the early stages of PD neuropathology. This model might prove very useful to investigate early neurodegenerative events in the nigrostriatal DAergic system and to study the effects of potential treatment strategies counteracting the early PD cellular changes. © 2013 IOS Press and the authors. All rights reserved.

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