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The brain's sensory lateralization involves the processing of information from the sensory organs primarily in one hemisphere. This can improve brain efficiency by reducing interference and duplication of neural circuits. For species that rely on successful interaction among family partners, such as geese, lateralization can be advantageous. However, at the group level, one-sided biases in sensory lateralization can make individuals predictable to competitors and predators. We investigated lateral preferences in the positioning of pair mates of Greater white-fronted geese Anser albifrons albifrons. Using GPS-GSM trackers, we monitored individual geese in flight throughout the year. Our findings indicate that geese exhibit individual lateral biases when viewing their mate in flight, but the direction of these biases varies among individuals. We suggest that these patterns of visual lateralization could be an adaptive trait for the species with long-term social monogamy, high levels of interspecies communication and competition, and high levels of predator and hunting pressure. [ABSTRACT FROM AUTHOR]

The quality and quantity of music therapy research are increasing, as are the number of systematic reviews and meta-analyses. However, the latter often define the effect of music therapy treatment as inconclusive. This is frequently due to a lack of clear description of the intervention or the core function of music. Clearly described music therapy interventions might lead to improved treatment fidelity. This article offers a possible solution in three parts. First, limitations in music therapy research are discussed. Second, the design for a format of a practice-based intervention description is explained. In the third part of the article, an example illustrates the use of the format. The suggested micro-intervention format could lead to a greater reliability in empirical research through the recognition of the working-mechanisms of music therapy intervention at a micro-level. The micro-intervention format was created in collaboration with practicing music therapists, Master students, and a board member for scientific innovation of a professional association. The micro-intervention format allows music therapists to describe music therapy interventions in detail, including the intervention and its musical working-mechanisms. The format is intended to guide music therapists to execute their intervention in comparable manners, which in the case of a scientific study could improve research fidelity. "Music therapeutic guidance to reduce agitation in dementia care using improvisation and familiar songs" is used to illustrate the micro-intervention format. Development and dissemination of music therapy micro-interventions could lead to improved research outcomes and strengthen the evidence-based foundation of the profession. [ABSTRACT FROM AUTHOR]

Early brain activity, measured using amplitude-integrated EEG (aEEG), is correlated with neurodevelopmental outcome in preterm newborns. F2-isoprostanes (IPs) are early biomarkers predictive for brain damage. We aimed to investigate the relationship between perinatal IPs concentrations and quantitative aEEG measures in preterm newborns. Thirty-nine infants (gestational age (GA) 24–27 ± 6 weeks) who underwent neuromonitoring using aEEG during the first two days after birth were enrolled. The rate of spontaneous activity transients per minute (SAT rate) and inter-SAT interval (ISI) in seconds were computed. Two postnatal time-points were examined: within 12 h (day 1) and between 24 and 48 h (day 2). IPs were measured in plasma from cord blood (cb-IPs) and between 24 and 48 h (pl-IPs). Multivariable regression analyses were performed to assess the correlation between IPs and brain activity. Cb-IPs were not associated with SAT rate and ISI at day 1. Higher pl-IPs were followed by longer ISI (R = 0.68; p = 0.034) and decreased SAT rate (R = 0.58; p = 0.007) at day 2 after adjusting for GA, FiO2 and IVH. Higher pl-IPs levels are associated with decreased functional brain activity. Thus, pl-IPs may represent a useful biomarker of brain vulnerability in high-risk infants. [ABSTRACT FROM AUTHOR]

Background: Individual differences in the risk to develop dementia remain poorly understood. These differences may partly be explained through reserve, which is the ability to buffer cognitive decline due to neuropathology and age.Objective: To determine how much early and late-life cognitive reserve (CR) and brain reserve (BR) contribute to the risk of dementia.Methods: 4,112 dementia-free participants (mean age = 66.3 years) from the Rotterdam Study were followed up for on average 6.0 years. Early-life CR and BR were defined as attained education and intracranial volume, respectively. Late-life CR was derived through variance decomposition based on cognition. Late-life BR was set as the total non-lesioned brain volume divided by intracranial volume.Results: Higher early-life CR (hazard ratio = 0.48, 95% CI = [0.21; 1.06]) but not early-life BR associated with a lower risk of incident dementia. Higher late-life CR (hazard ratio = 0.57, 95% CI = [0.48; 0.68]) and late-life BR (hazard ratio = 0.54, 95% CI = [0.43; 0.68]) also showed lower levels of dementia. Combining all proxies into one model attenuated the association between early-life CR and dementia (hazard ratio = 0.56, 95% CI = [0.25; 1.25]) whereas the other associations were unaffected. These findings were stable upon stratification for sex, age, and APOEɛ4. Finally, high levels of late-life CR and BR provided additive protection against dementia.Conclusion: The findings illustrate the importance of late-life over early-life reserve in understanding the risk of dementia, and show the need to study CR and BR conjointly. [ABSTRACT FROM AUTHOR]

Introduction: Recent fMRI studies have revealed altered activations in key regions for threat and affective processing of pain in motor imagination tasks. Yet, research in this vein is still lacking in people with chronic whiplash (CWAD). Methods: Sixty CWAD and 32 pain-free participants were included. In the scanner, participants were presented with pictures divided into 3 categories (5 weight bearing, 5 non-weight bearing and 5 neutral pictures) taken from the Pictorial Fear of Activity Scale-Cervical***questionnaire (jittered event-related design). After the scanning, participants were asked to rate each picture in terms of worry, desire to avoidance, anxiety, expected pain. SPM software was used for pre-processing and analysis of the fMRI data. Results: Whole brain analysis revealed greater activation in CWAD for the contrast weight bearing versus neutral pictures in planum temporale/parietal operculum, post/pre-central gyrus, frontal pole, precuneus and posterior cingulate. CWAD have greater activation in precuneus and cerebellum in the non-weight bearing versus neutral contrast. CWAD scored pictures higher than controls, but no correlation between scores and the identified clusters was found. Discussion: The results from this study allow for a better understanding of the maladaptive pain cognitions associated with CWAD by investigating the underlying neural activity alterations. Process evaluation: Several challenges were encountered along the way (data collection and analyses) as this was my first fMRI study. [ABSTRACT FROM AUTHOR]

Objective: Early electroencephalography measures contribute to outcome prediction of comatose patients after cardiac arrest. We present predictive values of a new cerebral recovery index, based on a combination of quantitative electroencephalography measures, extracted every hour, and combined by the use of a random forest classifier.Design: Prospective observational cohort study.Setting: Medical ICU of two large teaching hospitals in the Netherlands.Patients: Two hundred eighty-three consecutive comatose patients after cardiac arrest.Interventions: None.Measurements and Main Results: Continuous electroencephalography was recorded during the first 3 days. Outcome at 6 months was dichotomized as good (Cerebral Performance Category 1-2, no or moderate disability) or poor (Cerebral Performance Category 3-5, severe disability, comatose, or death). Nine quantitative electroencephalography measures were extracted. Patients were randomly divided over a training and validation set. Within the training set, a random forest classifier was fitted for each hour after cardiac arrest. Diagnostic accuracy was evaluated in the validation set. The relative contributions of resuscitation parameters and patient characteristics were evaluated. The cerebral recovery index ranges from 0 (prediction of death) to 1 (prediction of full recovery). Poor outcome could be predicted at a threshold of 0.34 without false positives at a sensitivity of 56% at 12 hours after cardiac arrest. At 24 hours, sensitivity of 65% with a false positive rate of 6% was obtained. Good neurologic outcome could be predicted with sensitivities of 63% and 58% at a false positive rate of 6% and 7% at 12 and 24 hours, respectively. Adding patient characteristics was of limited additional predictive value.Conclusions: A cerebral recovery index based on a combination of intermittently extracted, optimally combined quantitative electroencephalography measures provides unequalled prognostic value for comatose patients after cardiac arrest and enables bedside EEG interpretation of unexperienced readers. [ABSTRACT FROM AUTHOR]

Background: Changes in reward processing are thought to be involved in the etiology of attention-deficit/ hyperactivity disorder (ADHD), as well as other developmental disorders. In addition, different forms of therapy for ADHD rely on reinforcement principles. As such, improved understanding of reward processing in ADHD could eventually lead to more effective treatment options. However, differences in reward processing may not be specific to ADHD, but may be a trans-diagnostic feature of disorders that involve ADHD-like symptoms. Methods: In this event-related fMRI study, we used a child-friendly version of the monetary incentive delay task to assess performance and brain activity during reward anticipation. Also, we collected questionnaire data to assess reward sensitivity in daily life. For final analyses, data were available for 27 typically developing children, 24 children with ADHD, and 25 children with an autism spectrum disorder (ASD) and ADHD symptoms. Results: We found decreased activity in ventral striatum during anticipation of reward in children with ADHD symptoms, both for children with ADHD as their primary diagnosis and in children with autism spectrum disorder and ADHD symptoms. We found that higher parent-rated sensitivity to reward was associated with greater anticipatory activity in ventral striatum for children with ADHD symptoms. In contrast, there was no relationship between the degree of ADHD symptoms and activity in ventral striatum. Conclusions: We provide evidence of biological and behavioral differences in reward sensitivity in children with ADHD symptoms, regardless of their primary diagnosis. Ultimately, a dimensional brain-behavior model of reward sensitivity in children with symptoms of ADHD may be useful to refine treatment options dependent on reward processing. [ABSTRACT FROM AUTHOR]

Native speakers of Dutch do not always adhere to prescriptive grammar rules in their daily speech. These grammatical norm violations can elicit emotional reactions in language purists, mostly high-educated people, who claim that for them these constructions are truly ungrammatical. However, linguists generally assume that grammatical norm violations are in fact truly grammatical, especially when they occur frequently in a language. In an fMRI study we investigated the processing of grammatical norm violations in the brains of language purists, and compared them with truly grammatical and truly ungrammatical sentences. Grammatical norm violations were found to be unique in that their processing resembled not only the processing of truly grammatical sentences (in left medial Superior Frontal Gyrus and Angular Gyrus), but also that of truly ungrammatical sentences (in Inferior Frontal Gyrus), despite what theories of grammar would usually lead us to believe. [ABSTRACT FROM AUTHOR]

BACKGROUND: Food cues are omnipresent and may trigger overconsumption. In the past 2 decades, the prevalence of childhood obesity has increased dramatically. Because children's brains are still developing, especially in areas important for inhibition, children may be more susceptible than adults to tempting food cues. OBJECTIVE: We examined potential developmental differences in children's and adults' responses to food cues to determine how these responses relate to weight status. DESIGN: We included 27 children aged 10-12 y and 32 adults aged 32-52 y. Functional magnetic resonance imaging data were acquired during a food-viewing task in which unhealthy and healthy food pictures were presented. RESULTS: Children had a stronger activation in the left precentral gyrus than did adults in response to unhealthy compared with healthy foods. In children, unhealthy foods elicited stronger activation in the right inferior temporal and middle occipital gyri, left precentral gyrus, bilateral opercular part of the inferior frontal gyrus, left hippocampus, and left middle frontal gyrus. Adults had stronger activation in the bilateral middle occipital gyrus and the right calcarine sulcus for unhealthy compared with healthy foods. Children with a higher body mass index (BMI) had lower activation in the bilateral dorsolateral prefrontal cortex while viewing unhealthy compared with healthy foods. In adults there was no correlation between BMI and neural response to unhealthy compared with healthy foods. CONCLUSIONS: Unhealthy foods might elicit more attention both in children and in adults. Children had stronger activation while viewing unhealthy compared with healthy foods in areas involved in reward, motivation, and memory. Furthermore, children activated a motivation and reward area located in the motor cortex more strongly than adults did in response to unhealthy foods. Finally, children with a higher BMI had less activation in inhibitory areas in response to unhealthy foods, which may mean they are more susceptible to tempting food cues. This trial was registered at www.trialregister.nl as NTR4255. [ABSTRACT FROM AUTHOR]

Background: Sex differences in performance and regional brain activity during mental rotation have been reported repeatedly and reflect organizational and activational effects of sex hormones. We investigated whether adolescent girls with gender dysphoria (GD), before and after 10 months of testosterone treatment, showed male-typical brain activity during a mental rotation task (MRT). Methods: Girls with GD underwent fMRI while performing the MRT twice: when receiving medication to suppress their endogenous sex hormones before onset of testosterone treatment, and 10 months later during testosterone treatment. Two age-matched control groups participated twice as well. Results: We included 21 girls with GD, 20 male controls and 21 female controls in our study. In the absence of any group differences in performance, control girls showed significantly increased activation in frontal brain areas compared with control boys (pFWE = 0.012). Girls with GD before testosterone treatment differed significantly in frontal brain activation from the control girls (pFWE = 0.034), suggesting a masculinization of brain structures associated with visuospatial cognitive functions. After 10 months of testosterone treatment, girls with GD, similar to the control boys, showed increases in brain activation in areas implicated in mental rotation. Limitations: Since all girls with GD identified as gynephilic, their resemblance in spatial cognition with the control boys, who were also gynephilic, may have been related to their shared sexual orientation rather than their shared gender identity. We did not account for menstrual cycle phase or contraceptive use in our analyses. Conclusion: Our findings suggest atypical sexual differentiation of the brain in natal girls with GD and provide new evidence for organizational and activational effects of testosterone on visuospatial cognitive functioning. [ABSTRACT FROM AUTHOR]

Background: The positive relationship between cognitive and physical performance has been widely established. The influence of brain structure on both domains has been shown as well.Objective: We studied whether the relationship between brain structure and physical performance is independent of cognitive performance.Methods: This was a cross-sectional analysis of 297 middle-aged to older adults (mean age ± SD 65.4 ± 6.8 years). Memory function, executive function and physical performance measured by the Tandem Stance Test, Chair Stand Test, 4-meter walk and 25-meter walk were assessed. Magnetic resonance imaging was available in 237 participants and used to determine the (sub)cortical gray matter, white matter, hippocampal and basal ganglia volumes and the presence of cerebral small-vessel disease, i.e. white matter hyperintensities, cerebral microbleeds (CMBs) and lacunar infarcts (LIs). Regression analysis was used adjusting for age, gender, education and whole-brain volume. A Bonferroni correction was applied considering p values <0.017 as statistically significant.Results: Poor memory function was associated with a slower 4-meter walking speed (p < 0.01). No association was found between brain structure and cognitive performance. The presence of CMBs and LIs was associated with a slower 25-meter walking speed (p < 0.001). This result did not change after additional adjustment for cognitive performance.Conclusions: In middle-aged to older adults, CMBs and LIs are associated with walking speed independent of cognitive performance. This emphasizes the clinical relevance of identifying each of the possible underlying mechanisms of physical performance, which is required for the development of timely and targeted therapies. [ABSTRACT FROM AUTHOR]

We investigated the effects of age on proactive and reactive cognitive control in a large population sample of 809 individuals, ranging in age between 5 and 97 years. For that purpose, we used an anticue paradigm, which required a consistent remapping of cue location and response hand: Left-sided cues required right-hand responses and vice versa. After a random preparation interval of 100-850 ms, these anticues were followed by a target stimulus, which prompted a response with the index or middle finger of 1 of 2 hands. A neutral control condition involved uninformative cues, indicating all 4 possible response locations. The primary outcome measure was the difference between neutral and anticue reaction time (RT). Negative values indicated RT costs of the anticue, relative to the neutral condition, reflecting reactive cognitive control. Positive values indicated RT benefits, reflecting proactive cognitive control. Results were twofold. First, the switch from RT costs to benefits took place at longer preparation intervals in the youngest and oldest age groups than in the intermediate age groups. Second, irrespective of preparation interval, anticue performance followed an inverted U-shaped trajectory as a function of age, with a relatively steep improvement during childhood and adolescence, relative stability between 26 and 60 years, and a slightly accelerating decline into old age. Both patterns of results suggest an age-related transition from a primarily reactive, to a primarily proactive mode of cognitive control in early life and back again from a primarily proactive, to a primarily reactive mode of control in later life. [ABSTRACT FROM AUTHOR]

Background: Abnormal brain activations during processing of emotional facial expressions in depressed patients have been demonstrated. We investigated the natural course of brain activation in response to emotional faces in depression, indexed by functional magnetic resonance imaging (fMRI) scans preceding and following change in depressive state. We hypothesized a decrease in activation in the amygdala, anterior cingulate cortex (ACC), and insula with a decrease in depressive pathology.Methods: A 2-year longitudinal fMRI study was conducted as part of the Netherlands Study of Depression and Anxiety. We included 32 healthy controls and 49 depressed patients. During the second scan, 27 patients were in remission (remitters), the other 22 were not (nonremitters). All participants viewed faces with emotional expressions during scanning.Results: Rostral ACC activation during processing of happy faces was predictive of a decrease in depressive state (PFWE = .003). In addition, remitters showed decreased activation of the insula over time (PFWE = .016), specifically during happy faces. Nonremitters displayed increased abnormalities in emotion recognition circuitry during the second scan compared to the first. No effect of selective serotonin reuptake inhibitor use was observed.Conclusions: Our results demonstrate that rostral ACC activation may predict changes in depressive state even at 2-year outcome. The association between change in depressed state and change in insula activation provides further evidence for the role of the insula in a network maintaining emotional and motivational states. [ABSTRACT FROM AUTHOR]

Background: The goals of intentional curative pediatric epilepsy surgery are to achieve seizure-freedom and antiepileptic drug (AED) freedom. Retrospective cohort studies have indicated that early postoperative AED withdrawal unmasks incomplete surgical success and AED dependency sooner, but not at the cost of long-term seizure outcome. Moreover, AED withdrawal seemed to improve cognitive outcome. A randomized trial is needed to confirm these findings. We hypothesized that early AED withdrawal in children is not only safe, but also beneficial with respect to cognitive functioning.Design: This is a multi-center pragmatic randomized clinical trial to investigate whether early AED withdrawal improves cognitive function, in terms of attention, executive function and intelligence, quality of life and behavior, and to confirm safety in terms of eventual seizure freedom, seizure recurrences and "seizure and AED freedom." Patients will be randomly allocated in parallel groups (1:1) to either early or late AED withdrawal. Randomization will be concealed and stratified for preoperative IQ and medical center. In the early withdrawal arm reduction of AEDs will start 4 months after surgery, while in the late withdrawal arm reduction starts 12 months after surgery, with intended complete cessation of drugs after 12 and 20 months respectively. Cognitive outcome measurements will be performed preoperatively, and at 1 and 2 years following surgery, and consist of assessment of attention and executive functioning using the EpiTrack Junior test and intelligence expressed as IQ (Wechsler Intelligence Scales). Seizure outcomes will be assessed at 24 months after surgery, and at 20 months following start of AED reduction. We aim to randomize 180 patients who underwent anticipated curative epilepsy surgery below 16 years of age, were able to perform the EpiTrack Junior test preoperatively, and have no predictors of poor postoperative seizure prognosis (multifocal magnetic resonance imaging (MRI) abnormalities, incomplete resection of the lesion, epileptic postoperative electroencephalogram (EEG) abnormalities, or more than three AEDs at the time of surgery).Discussion: Growing experience with epilepsy surgery has changed the view towards postoperative medication policy. In a European collaboration, we designed a multi-center pragmatic randomized clinical trial comparing early with late AED withdrawal to investigate benefits and safety of early AED withdrawal. The TTS trial is supported by the Dutch Epilepsy Fund (NL 08-10) ISRCTN88423240/ 08/05/2013. [ABSTRACT FROM AUTHOR]

Background: Intra-operative electrocorticography, based on interictal spikes and spike patterns, is performed to optimize delineation of the epileptogenic tissue during epilepsy surgery. High frequency oscillations (HFOs, 80-500 Hz) have been identified as more precise biomarkers for epileptogenic tissue. The aim of the trial is to determine prospectively if ioECoG-tailored surgery using HFOs, instead of interictal spikes, is feasible and will lead to an equal or better seizure outcome. METHODS\Design: We present a single-blinded multi-center randomized controlled trial "The HFO Trial" including patients with refractory focal epilepsy of all ages who undergo surgery with intra-operative electrocorticography. Surgery is tailored by HFOs (arm 1) or interictal spikes (arm 2) in the intra-operative electrocorticography. Primary outcome is post-operative outcome after 1 year, dichotomized in seizure freedom (Engel 1A and 1B) versus seizure recurrence (Engel 1C-4). Secondary outcome measures are the volume of resected tissue, neurologic deficits, surgical duration and complications, cognition and quality of life. The trial has a non-inferiority design to test feasibility and at least equal performance in terms of surgical outcome. We aim to include 78 patients within 3 years including 1 year follow-up. Results are expected in 2018.Discussion: This trial provides a transition from observational research towards clinical interventions using HFOs. We address methodological difficulties in designing this trial. We expect that the use of HFOs as a biomarker for tailoring will increase the success rate of epilepsy surgery while reducing resection volume. This may reduce neurological deficits and yield a better quality of life. Future technical developments, such as validated automatic online HFO identification, could, together with the attained clinical knowledge, lead to a new objective tailoring approach in epilepsy surgery.Trial Registration: This trial is registered at the US National Institutes of Health (ClinicalTrials.gov) #NCT02207673 (31 July 2014) and the Central Committee on Research Involving Human Subjects, The Netherlands #NL44257.041.13 (18 March 2014). [ABSTRACT FROM AUTHOR]

Background: Response time variability (RTV) is consistently increased in patients with attention-deficit/hyperactivity disorder (ADHD). A right-hemispheric frontoparietal attention network model has been implicated in these patients. The 3 main connecting fibre tracts in this network, the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and the cingulum bundle (CB), show microstructural abnormalities in patients with ADHD. We hypothesized that the microstructural integrity of the 3 white matter tracts of this network are associated with ADHD and RTV. Methods: We examined RTV in adults with ADHD by modelling the reaction time distribution as an exponentially modified Gaussian (ex-Gaussian) function with the parameters μ, σ and, the latter of which has been attributed to lapses of attention. We assessed adults with ADHD and healthy controls using a sustained attention task. Diffusion tensor imaging--derived fractional anisotropy (FA) values were determined to quantify bilateral microstructural integrity of the tracts of interest. Results: We included 100 adults with ADHD and 96 controls in our study. Increased τ was associated with ADHD diagnosis and was linked to symptoms of inattention. An inverse correlation of τ with mean FA was seen in the right SLF of patients with ADHD, but no direct association between the mean FA of the 6 regions of interest with ADHD could be observed. Limitations: Regions of interest were defined a priori based on the attentional network model for ADHD and thus we might have missed effects in other networks. Conclusion: This study suggests that reduced microstructural integrity of the right SLF is associated with elevated τ in patients with ADHD. [ABSTRACT FROM AUTHOR]

Meta-analyses suggest normalizing effects of methylphenidate on structural fronto-striatal abnormalities in patients with attention-deficit/hyperactivity disorder (ADHD). A subgroup of patients receives atypical antipsychotics concurrent with methylphenidate. Long-term safety and efficacy of combined treatment are unknown. The current study provides an initial investigation of structural brain correlates of combined methylphenidate and antipsychotic treatment in patients with ADHD. Structural magnetic resonance imaging was obtained in 31 patients who had received combined methylphenidate and antipsychotic treatment, 31 matched patients who had received methylphenidate but not antipsychotics, and 31 healthy controls (M age 16.7 years). We analyzed between-group effects in total cortical and subcortical volume, and in seven frontal cortical and eight subcortical-limbic volumes of interest, each involved in dopaminergic neurotransmission. Patients in the combined treatment group, but not those in the methylphenidate only group, showed a reduction in total cortical volume compared to healthy controls (Cohen's d = 0.69, p < 0.004), which was apparent in most frontal volumes of interest. Further, the combined treatment group, but not the methylphenidate group, showed volume reduction in bilateral ventral diencephalon ( Left Cohen's d = 0.48, p < 0.04; Right Cohen's d = 0.46, p < 0.05) and the left thalamus (Cohen's d = 0.47, p < 0.04). These findings may indicate antipsychotic treatment counteracting the normalizing effects of methylphenidate on brain structure. However, it cannot be ruled out that pre-existing clinical differences between both patient groups may have resulted in anatomical differences at the time of scanning. The absence of an untreated ADHD group hinders unequivocal interpretation and implications of our findings. [ABSTRACT FROM AUTHOR]

It has been shown that learning a new skill leads to structural changes in the brain. However, it is unclear whether it is the acquisition or continuous practicing of the skill that causes this effect and whether brain connectivity of patients with schizophrenia can benefit from such practice. We examined the effect of 6 months exercise on a stationary bicycle on the brain in patients with schizophrenia and healthy controls. Biking is an endemic skill in the Netherlands and thus offers an ideal situation to disentangle the effects of learning vs practice. The 33 participating patients with schizophrenia and 48 healthy individuals were assigned to either one of two conditions, ie, physical exercise or lifeasusual, balanced for diagnosis. Diffusion tensor imaging brain scans were made prior to and after intervention. We demonstrate that irrespective of diagnosis regular physical exercise of an overlearned skill, such as bicycling, significantly increases the integrity, especially of motor functioning related, white matter fiber tracts whereas life-as-usual leads to a decrease in fiber integrity. Our findings imply that exercise of an overlearned physical skill improves brain connectivity in patients and healthy individuals. This has important implications for understanding the effect of fitness programs on the brain in both healthy subjects and patients with schizophrenia. Moreover, the outcome may even apply to the nonphysical realm. [ABSTRACT FROM AUTHOR]

Glucose is the main fuel for the brain, and manipulation of the glucose supply may consequently affect brain function. The present review was conducted to provide an overview of studies that investigated the acute effects of glucose load on memory and other cognitive functions in elderly people. The effects of sucrose on cognition and suggested mechanisms were also explored. A total of twenty studies met the inclusion criteria. In the majority of studies, episodic memory was investigated and a beneficial role for glucose in that specific cognitive domain was suggested. Other cognitive domains, i.e., working memory, semantic memory, visual memory, information-processing speed, attention, executive function, and visual/spatial function, have been studied less frequently and evidence for a beneficial effect of glucose was equivocal. Mechanisms are suggested to be mainly related to the human body's need for glucose as a metabolic substrate for physiological mechanisms in both central and peripheral processes. [ABSTRACT FROM AUTHOR]

Developmental differences in dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and superior parietal cortex (SPC) activation are associated with differences in how children, adolescents, and adults learn from performance feedback in rule-learning tasks (Crone, Zanolie, Leijenhorst, Westenberg, & Rombouts, 2008). Both maturational differences and performance differences can potentially explain variance in functional brain activation. To disentangle those effects, we established strategy differences in the performance of participants on the task of Crone et al. (2008) by the application of latent mixture models (McLachlan & Peel, 2000). We found 4 categorically different strategies, which were divided across age groups. Both adults and adolescents were distributed among all strategy groups except for the worst performing one, whereas children were distributed among all strategy groups except for the best performing one. Strategy use was a mediator and largely explained the relation between age and variance in activation patterns in the DLPFC and the SPC but not in the ACC. These findings are interpreted vis-h-vis age versus performance predictors of brain development. [ABSTRACT FROM AUTHOR]

Aims To assess whether immunization attenuates nicotinic stimulation of the brain and elucidate brain and behavioural responses during exposure to smoking cues and a working memory task. Design Randomized, placebo-controlled parallel-group, repeated-measures design. Setting Maastricht University, the Netherlands. Participants Forty-eight male smokers were randomized to receive five injections with either 400 μg/ml of the 3′-aminomethylnicotine Pseudomonas aeruginosa r-Exoprotein-conjugated vaccine or placebo. Subjects were tested on two occasions, once after a nicotine challenge and once after a placebo challenge, and were asked to refrain from smoking 10 hours before testing. Measurements Reaction-times and accuracies were recorded during an n-back task. Moreover, regional blood oxygenated level-dependent ( BOLD) response was measured during this task and during smoking cue exposure. Findings Greater activation was found in response to smoking cues compared to neutral cues in bilateral trans-occipital sulcus ( P < 0.005); however, this effect did not survive correction for multiple comparisons. There was no difference in brain activity to smoking cues between the treatment groups and no effects of acute nicotine challenge were established. For the n-back task we found working memory load-sensitive increases in brain activity in several frontal and parietal areas ( P < 0.0025). However, no effects of immunization or nicotine challenge were observed. Conclusion No significant effects of immunization on brain activity in response to a nicotine challenge were established. Therefore this vaccine is not likely to be an effective aid in smoking cessation. [ABSTRACT FROM AUTHOR]

Background: Protein is indispensable in the human diet, and its intake appears tightly regulated. The role of sensory attributes of foods in protein intake regulation is far from clear. Objective: We investigated the effect of human protein status on neural responses to different food cues with the use of functional magnetic resonance imaging (fMRI). The food cues varied by taste category (sweet compared with savory) and protein content (low compared with high). In addition, food preferences and intakes were measured. Design: We used a randomized crossover design whereby 23 healthy women [mean±SD age: 22±2 y; mean±SD body mass index (in kg/m²): 22.5±1.8] followed two 16-d fully controlled dietary interventions involving consumption of either a low-protein diet (0.6 g protein ⋅ kg body weight-1 ⋅ d-1, ~7% of energy derived from protein, approximately half the normal protein intake) or a high-protein diet (2.2 g protein ⋅ kg body weight-1 ⋅ d-1 ~25% of energy, approximately twice the normal intake). On the last day of the interventions, blood oxygen level-dependent (BOLD) responses to odor and visual food cues were measured by using fMRI. The 2 interventions were followed by a 1-d ad libitum phase, during which a large array of food items was available and preference and intake were measured. Results: When exposed to food cues (relative to the control condition), the BOLD response was higher in reward-related areas (orbitofrontal cortex, striatum) in a low-protein state than in a high-protein state. Specifically, BOLD was higher in the inferior orbitofrontal cortex in response to savory food cues. In contrast, the protein content of the food cues did not modulate the BOLD response. A low protein state also increased preferences for savory food cues and increased protein intake in the ad libitum phase as compared with a high-protein state. Conclusions: Protein status modulates brain responses in reward regions to savory food cues. These novel findings suggest that dietary protein status affects taste category preferences, which could play an important role in the regulation of protein intake in humans. [ABSTRACT FROM AUTHOR]

We tested whether in 85 healthy adults (18-29 years) there is a relationship between grey-matter (GM) volume and autism and ADHD symptom severity. The structural MRI findings and autism and ADHD self-reports revealed that autism and ADHD symptom severity was correlated with GM volume in the left inferior frontal gyrus. Autism symptom-severity was correlated with the left posterior cingulate, ADHD with the right parietal lobe, right temporal frontal cortex, bilateral thalamus, and left hippocampus/amygdala complex. Symptom severity of both disorders form a continuum extending into the general population, but it seems to be an oversimplification to typify psychiatric disorders such as autism and ADHD solely as extremes of brain structure abnormalities. [ABSTRACT FROM AUTHOR]

BackgroundDepression has been associated with limbic hyperactivation and frontal hypoactivation in response to negative facial stimuli. Anxiety disorders have also been associated with increased activation of emotional structures such as the amygdala and insula. This study examined to what extent activation of brain regions involved in perception of emotional faces is specific to depression and anxiety disorders in a large community-based sample of out-patients.MethodAn event-related functional magnetic resonance imaging (fMRI) paradigm was used including angry, fearful, sad, happy and neutral facial expressions. One hundred and eighty-two out-patients (59 depressed, 57 anxiety and 66 co-morbid depression-anxiety) and 56 healthy controls selected from the Netherlands Study of Depression and Anxiety (NESDA) were included in the present study. Whole-brain analyses were conducted. The temporal profile of amygdala activation was also investigated.ResultsFacial expressions activated the amygdala and fusiform gyrus in depressed patients with or without anxiety and in healthy controls, relative to scrambled faces, but this was less evident in patients with anxiety disorders. The response shape of the amygdala did not differ between groups. Depressed patients showed dorsolateral prefrontal cortex (PFC) hyperactivation in response to happy faces compared to healthy controls.ConclusionsWe suggest that stronger frontal activation to happy faces in depressed patients may reflect increased demands on effortful emotion regulation processes triggered by mood-incongruent stimuli. The lack of strong differences in neural activation to negative emotional faces, relative to healthy controls, may be characteristic of the mild-to-moderate severity of illness in this sample and may be indicative of a certain cognitive-emotional processing reserve. [ABSTRACT FROM PUBLISHER]

Post-stroke shoulder pain (PSSP), traditionally regarded as purely nociceptive pain, is often persistent and the mechanisms underlying the pain complaints are not well understood. This explorative study is the first to address the possible changes in cortical somatosensory processing in patients with PSSP. Cortical potentials were recorded following intracutaneous electrostimulaton in stroke patients with chronic PSSP (n= 6), pain-free stroke patients (PF, n=14) and healthy controls (HC, n=20) using EEG. Amplitudes and latencies of both sensory discriminative (N90) as well as cognitive evaluative (N150, P200, the N150-P200 peak-to-peak difference and P300) evoked potential components were evaluated. Stroke was associated with reduced N150 and P300 amplitudes and increased N90, N150 and P300 latencies at both sides. Compared to PF and HC, the P200 and N150-P200 latencies were increased in PSSP patients after stimulation at both sides, even when comparing subgroups with similar lesion size and location. Stroke was associated with reduced sensory-discriminative as well as with reduced cognitive-evaluative cortical somatosensory processing. This reduction was more pronounced in patients with PSSP and may be related to the central effects of persistent nociceptive pain. [ABSTRACT FROM AUTHOR]

To measure activity during sleep, polysomnography and actigraphy are often used. The DynaPort MiniMod measures movement intensity and body position day and night. The goal was to examine the validity of the DynaPort MiniMod in assessing physical activity and body posture during sleep. In Study A, 10 healthy participants slept with the DynaPort MiniMod and the Actiwatch for one night. In Study B, 8 participants suspected of having Obstructive Sleep Apnoea Syndrome slept for one night with the DynaPort MiniMod and underwent complete polysomnography as part of the typical care protocol. In Study A, there was a significant moderate correlation (r = .70) between the movement scores of the Actiwatch and the DynaPort MiniMod. In Study B, a high intraclass correlation (r = .84) between body posture scores of the DynaPort MiniMod and the polysomnography position sensor was observed. The DynaPort MiniMod is a valid measurement device for physical activity during sleep. [ABSTRACT FROM AUTHOR]

Structural brain markers are studied extensively in the field of neurodegeneration, but are thought to occur rather late in the process. Functional measures such as functional connectivity are gaining interest as potentially more subtle markers of neurodegeneration. However, brain structure and function are also affected by 'normal' brain ageing. More information is needed on how functional connectivity relates to aging, particularly in the absence of overt neurodegenerative disease. We investigated the association of age with resting-state functional connectivity in 2878 non-demented persons between 50 and 95 years of age (54.1% women) from the population-based Rotterdam Study. We obtained nine well-known resting state networks using data-driven methodology. Within the anterior default mode network, ventral attention network, and sensorimotor network, functional connectivity was significantly lower with older age. In contrast, functional connectivity was higher with older age within the visual network. Between resting state networks, we found patterns of both increases and decreases in connectivity in approximate equal proportions. Our results reinforce the notion that the aging brain undergoes a reorganization process, and serves as a solid basis for exploring functional connectivity as a preclinical marker of neurodegenerative disease., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Temperament has been suggested to be influenced by genetic and environmental factors. The current study examined genetic shared environmental and unique environmental factors accounting for variation in Fear, Effortful Control (EC), and Frontal Asymmetry (FA) in 4- to 6-year-old children using bivariate behavioral genetic modeling. We included a total of 214 same-sex twin pairs: 127 monozygotic (MZ) and 87 dizygotic (DZ) pairs. FA was measured during a rest electroencephalogram (EEG) recording, and Fear and EC were measured using parent report. Results show that differences between twins were best explained by genetic factors (about a quarter of the variance) and unique environmental factors (about three quarters of the variance). However, the cross-trait, within-twin correlations were not significant, implying no overlapping genetic or environmental factors on Fear and EC or on Fear and FA. Future research should try to elucidate the large role of unique environmental factors in explaining variance in these temperament-related traits., (Copyright © 2018 Elsevier Inc. All rights reserved.)

There is a consensus among language researchers that people can predict upcoming language. But do people always predict when comprehending language? Notions that "brains … are essentially prediction machines" certainly suggest so. In three eye-tracking experiments we tested this view. Participants listened to simple Dutch sentences ('Look at the displayed bicycle') while viewing four objects (a target, e.g. a bicycle, and three unrelated distractors). We used the identical visual stimuli and the same spoken sentences but varied speech rates, preview time, and participant instructions. Target nouns were preceded by definite gender-marked determiners, which allowed participants to predict the target object because only the targets but not the distractors agreed in gender with the determiner. In Experiment 1, participants had four seconds preview and sentences were presented either in a slow or a normal speech rate. Participants predicted the targets as soon as they heard the determiner in both conditions. Experiment 2 was identical except that participants were given only a one second preview. Participants predicted the targets only in the slow speech condition. Experiment 3 was identical to Experiment 2 except that participants were explicitly told to predict. This led only to a small prediction effect in the normal speech condition. Thus, a normal speech rate only afforded prediction if participants had an extensive preview. Even the explicit instruction to predict the target resulted in only a small anticipation effect with a normal speech rate and a short preview. These findings are problematic for theoretical proposals that assume that prediction pervades cognition., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Weight loss after bariatric surgery (BS) is often associated with improved cognition and structural brain recovery. However, improved cognition after BS is not always exhibited by patients, in fact, in some cases there is even a decline in cognition. Long-term consequences of BS weight loss, in terms of obesity and related diseases, can be hard to determine due to studies having short follow-up periods and small sample sizes.The aim of the BARICO study ( BA riatric surgery R ijnstate and Radboudumc neuro I maging and C ognition in O besity) is to determine the long-term effect of weight loss after BS on brain function and structure, using sensitive neuropsychological tests and (functional) MRI ((f)MRI). Secondary study endpoints are associated with changes in metabolic and inflammation status of adipose tissue, liver and gut, in relation to brain structure and function. Also, the possible correlation between weight loss, gut microbiota composition change and neuropsychological outcomes will be investigated., Methods and Analysis: Data from 150 Dutch BS patients (ages between 35 and 55, men and women) will be collected at various time points between 2 months before and up to 10 years after surgery. Neuropsychological tests, questionnaires, blood, faeces and tissue samples will be collected before, during and after surgery to measure changes in cognition, microbiota, metabolic activity and inflammation over time. A subgroup of 75 participants will undergo (f)MRI in relation to executive functioning (determined by the Stroop task), grey and white matter volumes and cerebral blood flow. Regression analyses will be used to explore associations between weight loss and outcome measures., Ethics and Dissemination: This study has been approved by the medical review ethics committee CMO Region Arnhem and Nijmegen (NL63493.091.17). Research findings will be published in peer-reviewed journals and at conferences., Trial Registration Number: NTR7288., Competing Interests: Competing interests: Not required., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Despite a growing body of evidence, the role of the gut microbiome in cardiovascular diseases is still unclear. Here, we present a systems-genome-wide and metagenome-wide association study on plasma concentrations of 92 cardiovascular-disease-related proteins in the population cohort LifeLines-DEEP. We identified genetic components for 73 proteins and microbial associations for 41 proteins, of which 31 were associated to both. The genetic and microbial factors identified mostly exert additive effects and collectively explain up to 76.6% of inter-individual variation (17.5% on average). Genetics contribute most to concentrations of immune-related proteins, while the gut microbiome contributes most to proteins involved in metabolism and intestinal health. We found several host-microbe interactions that impact proteins involved in epithelial function, lipid metabolism, and central nervous system function. This study provides important evidence for a joint genetic and microbial effect in cardiovascular disease and provides directions for future applications in personalized medicine.

The 2017 annual symposium organized by the University Medical Center Groningen in The Netherlands focused on the role of the gut microbiome in human health and disease. Experts from academia and industry examined interactions of prebiotics, probiotics, or vitamins with the gut microbiome in health and disease, the development of the microbiome in early-life and the role of the microbiome on the gut-brain axis. The gut microbiota changes dramatically during pregnancy and intrinsic factors (such as stress), in addition to extrinsic factors (such as diet, and drugs) influence the composition and activity of the gut microbiome throughout life. Microbial metabolites, e.g. short-chain fatty acids affect gut-brain signaling and the immune response. The gut microbiota has a regulatory role on anxiety, mood, cognition and pain which is exerted via the gut-brain axis. Ingestion of prebiotics or probiotics has been used to treat a range of conditions including constipation, allergic reactions and infections in infancy, and IBS. Fecal microbiota transplantation (FMT) highly effective for treating recurrent Clostridium difficile infections. The gut microbiome affects virtually all aspects of human health, but the degree of scientific evidence, the models and technologies and the understanding of mechanisms of action vary considerably from one benefit area to the other. For a clinical practice to be broadly accepted, the mode of action, the therapeutic window, and potential side effects need to thoroughly be investigated. This calls for further coordinated state-of-the art research to better understand and document the human gut microbiome's effects on human health.

Resting-state functional connectivity patterns are highly stable over time within subjects. This suggests that such 'functional fingerprints' may have strong genetic component. We investigated whether the functional (FC) or effective (EC) connectivity patterns of one monozygotic twin could be used to identify the co-twin among a larger sample and determined the overlap in functional fingerprints within monozygotic (MZ) twin pairs using resting state magnetoencephalography (MEG). We included 32 cognitively normal MZ twin pairs from the Netherlands Twin Register who participate in the EMIF-AD preclinAD study (average age 68 years). Combining EC information across multiple frequency bands we obtained an identification rate over 75%. Since MZ twin pairs are genetically identical these results suggest a high genetic contribution to MEG-based EC patterns, leading to large similarities in brain connectivity patterns between two individuals even after 60 years of life or more.

Cerebral dominance of language function and hand preference are suggested to be heritable traits with possible shared genetic background. However, joined genetic studies of these traits have never been conducted. We performed a genetic linkage study in 37 multigenerational human pedigrees of both sexes (consisting of 355 subjects) enriched with left-handedness in which we also measured language lateralization. Hand preference was measured with the Edinburgh Handedness Inventory, and language lateralization was measured with functional transcranial Doppler during language production. The estimated heritability of left-handedness and language lateralization in these pedigrees is 0.24 and 0.31, respectively. A parametric major gene model was tested for left-handedness. Nonparametric analyses were performed for left-handedness, atypical lateralization, and degree of language lateralization. We did not observe genome-wide evidence for linkage in the parametric or nonparametric analyses for any of the phenotypes tested. However, multiple regions showed suggestive evidence of linkage. The parametric model showed suggestive linkage for left-handedness in the 22q13 region [heterogeneity logarithm of odds (HLOD) = 2.18]. Nonparametric multipoint analysis of left-handedness showed suggestive linkage in the same region [logarithm of odds (LOD) = 2.80]. Atypical language lateralization showed suggestive linkage in the 7q34 region (LODMax = 2.35). For strength of language lateralization, we observed suggestive linkage in the 6p22 (LODMax = 2.54), 7q32 (LODMax = 1.93), and 9q33 (LODMax = 2.10) regions. We did not observe any overlap of suggestive genetic signal between handedness and the extent of language lateralization. The absence of significant linkage argues against the presence of a major gene coding for both traits; rather, our results are suggestive of these traits being two independent polygenic complex traits., (Copyright © 2015 the authors 0270-6474/15/358730-07$15.00/0.)

Intraoperative direct electrical stimulation (DES) is increasingly used in patients operated on for tumours in eloquent areas. Although a positive impact of DES on postoperative linguistic outcome is generally advocated, information about the neurolinguistic methods applied in awake surgery is scarce. We developed for the first time a standardised Dutch linguistic test battery (measuring phonology, semantics, syntax) to reliably identify the critical language zones in detail. A normative study was carried out in a control group of 250 native Dutch-speaking healthy adults. In addition, the clinical application of the Dutch Linguistic Intraoperative Protocol (DuLIP) was demonstrated by means of anatomo-functional models and five case studies. A set of DuLIP tests was selected for each patient depending on the tumour location and degree of linguistic impairment. DuLIP is a valid test battery for pre-, intraoperative and postoperative language testing and facilitates intraoperative mapping of eloquent language regions that are variably located., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Abstract: Knowing how to adapt your behavior based on feedback lies at the core of successful learning. We investigated the relation between brain function, grey matter volume, educational level and IQ in a Dutch adolescent sample. In total 45 healthy volunteers between ages 13 and 16 were recruited from schools for pre-vocational and pre-university education. For each individual, IQ was estimated using two subtests from the WISC-III-R (similarities and block design). While in the magnetic resonance imaging (MRI) scanner, participants performed a probabilistic learning task. Behavioral comparisons showed that participants with higher IQ used a more adaptive learning strategy after receiving positive feedback. Analysis of neural activation revealed that higher IQ was associated with increased activation in DLPFC and dACC when receiving positive feedback, specifically for rules with low reward probability (i.e., unexpected positive feedback). Furthermore, VBM analyses revealed that IQ correlated positively with grey matter volume within these regions. These results provide support for IQ-related individual differences in the developmental time courses of neural circuitry supporting feedback-based learning. Current findings are interpreted in terms of a prolonged window of flexibility and opportunity for adolescents with higher IQ scores. [Copyright &y& Elsevier]

Because the publication of several prospective studies on near-death experience (NDE) in survivors of cardiac arrest have shown strikingly similar results and conclusions, the phenomenon of the NDE can no longer be scientifically ignored. The NDE is an authentic experience that cannot be simply reduced to imagination, fear of death, hallucination, psychosis, the use of drugs, or oxygen deficiency. Patients appear to be permanently changed by an NDE during a cardiac arrest of only some minutes' duration. It is a scientific challenge to discuss new hypotheses that could explain the possibility of a clear and enhanced consciousness--with memories, self-identity, cognition, and emotions--during a period of apparent coma. The current materialistic view of the relationship between consciousness and the brain, as held by most physicians, philosophers, and psychologists, seems to be too restricted for a proper understanding of this phenomenon. There are good reasons to assume that our consciousness, with the continuous experience of self, does not always coincide with the functioning of our brain: enhanced or nonlocal consciousness, with unaltered self-identity, apparently can be experienced independently from the lifeless body. People are convinced that the self they experienced during their NDE is a reality and not an illusion., (© 2011 New York Academy of Sciences.)

We investigated the processing of violations of the verb position in Dutch, in a group of healthy subjects, by measuring event-related potentials (ERPs) through electroencephalography (EEG). In Dutch, the base position of the verb is clause final, but in matrix clauses, the finite verb is in second position, a construction known as Verb Second. In embedded clauses, the finite verb remains in its clause-final base position. The results show that ungrammatical placement of finite verbs in second position in embedded clauses yields a P600 response, which suggests that the parser treats this type of violation as a clear syntactic anomaly. This is in contrast to accounts by which a general preference for subject-verb-object word order in languages like Dutch is reflected by an absence of P600 effects in response to violations of Verb Second.

This paper shows how Arthur Benton's excellent research in the field of neuropsychological topics like hemispheric specialization, Gerstmann syndrome, aphasia, prosopagnosia and visuospatial deficits has influenced the development of the field of neuropsychology in The Netherlands. Also, his outstanding methodological knowledge and clinical experience have had an enormously significant impact on neuropsychological assessment in this country. Benton's knowledge about the different topics in neuropsychology was tremendous, while at the same time he was always critical and aware of findings he was not able to understand.

The present study investigated morphological priming in Dutch and its time course in overt speech production using a long-lag priming paradigm. Prime words were compounds that were morphologically related to a picture name (e.g. the word jaszak, 'coat pocket' was used for a picture of a coat; Dutch jas) or form-related monomorphemic words (e.g. jasmijn, 'jasmine'). The morphologically related compounds could be semantically transparent (e.g. eksternest, 'magpie nest') or opaque (e.g. eksteroog, lit. 'magpie eye', 'corn', for a picture of a magpie, Dutch ekster). Behavioral and event-related potential (ERP) data were collected in two sessions. The production of morphologically related and complex words facilitated subsequent picture naming and elicited a reduced N400 compared with unrelated prime words. The effects did not differ for transparent and opaque relations. Mere form overlap between a prime word and a target picture name did not affect picture naming. These results extend previous findings from German to another language and demonstrate the feasibility of measuring cognitive ERP components during overt speech. Furthermore, the results suggest that morphological priming in language production cannot be reduced to semantic and phonological processing. The time course of these priming effects as reflected in the ERP measure is in accordance with a meta-analytic temporal estimate of morphological encoding in speaking [Indefrey, P., & Levelt, W.J.M. (2004). The spatial and temporal signatures of word production components. Cognition, 92, 101-144.] suggesting that morphological relations are encoded at the word form level.

Reduced cerebral perfusion may contribute to the development of cerebrovascular and neurodegenerative diseases. Little is known on cerebral perfusion in the general population, as most measurement techniques are too invasive for application in large groups of healthy individuals. Total cerebral blood flow (tCBF) can be noninvasively measured by magnetic resonance imaging (MRI) but is highly correlated with brain volume. We calculated total brain perfusion by dividing tCBF by brain volume, and we investigated determinants of total brain perfusion in comparison with tCBF. Secondly, we studied whether persons with a low tCBF or low total brain perfusion have a larger volume of white matter lesions (WML). This study is based on 892 persons aged 60 to 91 years from the Rotterdam Study, a population-based cohort study. We performed two-dimensional (2D) phase-contrast MRI for tCBF measurement. Brain volume and WML volume were quantitatively assessed. Cardiovascular determinants were assessed by interview and physical examination. We assessed associations between cardiovascular determinants and flow measures with linear regression models, adjusted for age and sex. Associations between tCBF or total brain perfusion and WML volume were assessed using general linear models. We found that determinants of tCBF and total brain perfusion differed largely due to the large influence of brain volume on tCBF values. Persons with low total brain perfusion had a significantly larger WML volume compared with those with high total brain perfusion. Prospective studies are required to unravel whether hypoperfusion contributes to WML formation or that tissue damage, manifested by WML, leads to brain hypoperfusion.

The amplitude fluctuations of ongoing oscillations in the electroencephalographic (EEG) signal of the human brain show autocorrelations that decay slowly and remain significant at time scales up to tens of seconds. We call these long-range temporal correlations (LRTC). Abnormal LRTC have been observed in several brain pathologies, but it has remained unknown whether genetic factors influence the temporal correlation structure of ongoing oscillations. We recorded the ongoing EEG during eyes-closed rest in 390 monozygotic and dizygotic twins and investigated the temporal structure of ongoing oscillations in the alpha- and beta-frequency bands using detrended fluctuation analysis (DFA). The strength of LRTC was more highly correlated in monozygotic than in dizygotic twins. Statistical analysis attributed up to approximately 60% of the variance in DFA to genetic factors, indicating a high heritability for the temporal structure of amplitude fluctuations in EEG oscillations. Importantly, the DFA and EEG power were uncorrelated. LRTC in ongoing oscillations are robust, heritable, and independent of power, suggesting that LRTC and oscillation power are governed by distinct biophysical mechanisms and serve different functions in the brain. We propose that the DFA method is an important complement to classical spectral analysis in fundamental and clinical research on ongoing oscillations.

Aletta H. Jacobs was the first female physician in the Netherlands. In 1879, she defended her thesis which addressed the subject of localising brain functions. In it she described three neurological patients using systematic conventions highly resembling those in use today. Moreover, she discussed whether or not functions were regionally represented. Her discussion concluded in favour of localisation. These days, the concept of distributed networks goes beyond simple topographical representation. This is illustrated in the cerebral organisation of vision. It is possible to discern visual centres that are specialised in processing specific qualities such as colour or visual motion. An additional feature of such segregated processing streams is the presence of underlying connections to specific brain areas at a distance. Functioning as a node in multiple networks, one single brain region may potentially be involved in multiple functions. This depends on the interactions with other regions and on the actual dominance of information processing within such networks.

Based on qualitative and quantitative EEG findings, the psychotropic properties of GB-94, GC-46, and GC-94 were predicted. According to the EEG model, GB-94 was predicted to be similar to amitriptyline and GC-46 t( imipramine. GC-94 was found to be much less effective on the CNS than GB-94 and GC-46 and was predicted to have "stimulatory" clinical effects similar to desipramine. The clinical trials demonstrated that GB-94 is indeed an antidepressive psychotropic compound similar to amitriptyline. GB-94 in lower dosages was also found to be effective in anxiety syndromes. In some schizophrenics GB-94 showed some therapeutic effects, while in others it obviously exacerbrated the psychotic symptomatology. GC-94 was not found to be significantly effective in a heterogenous psychiatric population. Only slight improvement in some schizophrenic patients was observed However, a noticeable worsening in the symptomatology of manic and hypomanic patients was seen. The study demonstarted that GC-94 indeed has a central stimulatory effect, but no minor or major tranquilizer properties or sedative antidepressive qualities were observed. GC-46 was tried in only three subjects. Based on this pilot trial, no conclusion can be made about the psychotropic properties of this compound. Our quantitative pharmaco-EEG and clinical trials clearly demonstrated the significant value of quantitative EEG in early screening of psychoactive drugs in order to predict their clinical values and effective dosage ranges.

A practical science of the brain scarcely existed before the 17th century except in terms of gross anatomy. In all countries vitalistic concepts held sway, yielding only slowly to more materialistic views. These developed at a different pace in different countries, due, in each case, to the dominant philosophies of the time: the English empiricists; the French Enlightenment; the Italian and German schools of experimental neurophysiology. The last to accept the materialists' viewpoints was Russia, whose scientists imported them from their training in Western Europe in the 19th century. A brief outline is given of how the history of brain science parallels the history of ideas in the 17th, 18th and 19th centuries.

In this review a brief historical view on biomedical gerontological research in the Netherlands is given. In the sixties and seventies this research, started in 1953, was mainly done at the TNO Institute for Experimental Gerontology and devoted to the topics pathology, immunology and organ and cell physiology (mainly the liver). Current research mainly concentrates on the brain, the immune system, the liver, the cardiovascular system, the locomotor system and the eye. It can be concluded that due to the SOOM (Steering Committee for Research on Aging) and ZWO (Fundamental Scientific Research) the amount and quality of biomedical gerontological research in the Netherlands has greatly increased. It is hypothesized that in the near future no spectacular developments are to be expected. Nevertheless, in the long term, on the basis of advances in molecular biology, the mechanisms of the aging process may be elucidated. Consequently, pathological changes can be recognized so that diagnosis, prevention or therapy may be possible. Especially, the prevention or therapy of the Alzheimer's disease or of osteoporosis looks promising.