Enhanced activation of reward mediating prefrontal regions in response to food stimuli in Prader-Willi syndrome

Background

Individuals with Prader–Willi syndrome (PWS) exhibit severe disturbances in appetite regulation, including delayed meal termination, early return of hunger after a meal, seeking and hoarding food and eating of non‐food substances. Brain pathways involved in the control of appetite in humans are thought to include the hypothalamus, frontal cortex (including the orbitofrontal, ventromedial prefrontal, dorsolateral prefrontal and anterior cingulate areas), insula, and limbic and paralimbic areas. We hypothesised that the abnormal appetite in PWS results from aberrant reward processing of food stimuli in these neural pathways.

Methods

We compared functional MRI blood oxygen level dependent (BOLD) responses while viewing pictures of food in eight adults with PWS and eight normal weight adults after ingestion of an oral glucose load.

Results

Subjects with PWS demonstrated significantly greater BOLD activation in the ventromedial prefrontal cortex than controls when viewing food pictures. No significant differences were found in serum insulin, glucose or triglyceride levels between the groups at the time of the scan.

Conclusions

Individuals with PWS had an increased BOLD response in the ventromedial prefrontal cortex compared with normal weight controls when viewing pictures of food after an oral glucose load. These findings suggest that an increased reward value for food may underlie the excessive hunger in PWS, and support the significance of the frontal cortex in modulating the response to food in humans. Our findings in the extreme appetite phenotype of PWS support the importance of the neural pathways that guide reward related behaviour in modulating the response to food in humans.Prader–Willi syndrome (PWS) is the most commonly recognised genetic cause of childhood obesity. Approximately 70% of PWS cases are due to a genetic deletion on chromosome 15 (15q11–13), 25% of PWS cases are from a maternal uniparental disomy of chromosome 15 and the remaining cases result from imprinting defects.^1,2 This syndrome is characterised by infantile hypotonia, mental retardation, short stature, hypogonadism, hyperphagia and early onset obesity.³ The early onset morbid obesity is the most significant health problem experienced by individuals with PWS, as it is their primary cause of morbidity and mortality.Individuals with PWS typically have failure to thrive in infancy, which is followed by the onset of obesity at the age of 18–36 months, usually without a significant change in calories. Subsequently, these patients develop significant hyperphagia which worsens the obesity. By adulthood, significant hyperphagia is present in almost all individuals with PWS. These individuals may steal and hoard food, eat non‐food substances (pica behaviour) and, if given free access to food, will consume three to six times as much food as control subjects.^4,5 The hyperphagia appears refractory to psychopharmacological intervention. Additionally, individuals with PWS have delayed meal termination and earlier return of hunger after a previous meal.⁴ These appetite disturbances are thought to be primarily due to hypothalamic dysfunction, given the other hypothalamic abnormalities in PWS, including growth hormone deficiency, hypogonadotropic hypogonadism and temperature dysregulation.⁶ Indeed, a reduction in the number of cells in the paraventricular nucleus, including anorexigenic oxytocin neurons, has been seen in post‐mortem hypothalami.⁷While plasma levels of leptin, an anorexigenic hormone produced by adipose tissue, are appropriately elevated in PWS, multiple studies have shown other metabolic and hormonal abnormalities in PWS that may contribute to their hyperphagia.^8,9,10,11,12 However, the relative importance of these abnormalities and their relationship to brain defects in PWS remains unclear.As PWS represents an extreme appetite phenotype, study of this population could help elucidate the biological and neuroanatomical pathways that control appetite in humans and lead to a greater understanding of the pathophysiology of obesity. In vivo functional neuroimaging has recently been used to study the brain pathways involved in human appetite control.¹³ Positron emission tomography (PET) studies have highlighted changes in neuronal activity, as measured by regional resting cerebral blood flow, between fasted and fed states in several brain regions that may mediate satiety, including the hypothalamus, orbitofrontal cortex, insula and inferotemporal cortex, and limbic and paralimbic areas.¹³ The inter‐relationship of these areas is thought to be involved in reward, arousal, motivational, memory and emotional responses to food and eating. Both PET and functional MRI (fMRI) studies have demonstrated acute regional activity changes in these brain regions in response to food stimuli strongly supporting a role for the frontal cortex in the reward responses to food in healthy subjects.^14,15,16,17In a previous study using fMRI, we found that individuals with PWS showed a temporal delay in the resting hypothalamic and frontal cortex response to glucose ingestion (25 min) compared with both normal weight (10 min) and obese controls (15 min).¹⁸ We hypothesise that the increased appetite in PWS arising from neuroendocrine, particularly hypothalamic, defects results in abnormal reward processing in the brain that predisposes to excess caloric intake. This study, therefore, investigated the reward responses to food stimuli in PWS by using fMRI to evaluate the blood oxygen level dependent (BOLD) responses to food pictures in individuals with PWS compared with normal weight sibling controls after ingestion of an oral glucose load.     

Acute tryptophan loading decreases functional connectivity between the default mode network and emotion‐related brain regions

It has been shown that the functional architecture of the default mode network (DMN) can be affected by serotonergic challenges and these effects may provide insights on the neurobiological bases of depressive symptomatology. To deepen our understanding of this possible interplay, we used a double‐blind, randomized, cross‐over design, with a control condition and two interventions to decrease (tryptophan depletion) and increase (tryptophan loading) brain serotonin synthesis. Resting‐state fMRI from 85 healthy subjects was acquired for all conditions 3 hr after the ingestion of an amino acid mixture containing different amounts of tryptophan, the dietary precursor of serotonin. The DMN was derived for each participant and session. Permutation testing was performed to detect connectivity changes within the DMN as well as between the DMN and other brain regions elicited by the interventions. We found that tryptophan loading increased tryptophan plasma levels and decreased DMN connectivity with visual cortices and several brain regions involved in emotion and affect regulation (i.e., putamen, subcallosal cortex, thalamus, and frontal cortex). Tryptophan depletion significantly reduced tryptophan levels but did not affect brain connectivity. Subjective ratings of mood, anxiety, sleepiness, and impulsive choice were not strongly affected by any intervention. Our data indicate that connectivity between the DMN and emotion‐related brain regions might be modulated by changes in the serotonergic system. These results suggest that functional changes in the brain associated with different brain serotonin levels may be relevant to understand the neural bases of depressive symptoms.     

Volitional control of attention and brain activation in dual task performance

This study used functional MRI (fMRI) to examine the neural effects of willfully allocating one's attention to one of two ongoing tasks. In a dual task paradigm, participants were instructed to focus either on auditory sentence comprehension, mental rotation, or both. One of the major findings is that the distribution of brain activation was amenable to strategic control, such that the amount of activation per task was systematically related to the attention-dividing instructions. The activation in language processing regions was lower when attending to mental rotation than when attending to the sentences, and the activation in visuospatial processing regions was lower when attending to sentences than when attending to mental rotations. Additionally, the activation was found to be underadditive, with the dual-task condition eliciting less activation than the sum of the attend sentence and attend rotation conditions. We also observed a laterality shift across conditions within language-processing regions, with the attend sentence condition showing bilateral activation, while the dual task condition showed a left hemispheric dominance. This shift suggests multiple language-processing modes and may explain the underadditivity in activation observed in the current and previous studies.     

Brain reward system's alterations in response to food and monetary stimuli in overweight and obese individuals

The brain's reward system is crucial to understand obesity in modern society, as increased neural responsivity to reward can fuel the unhealthy food choices that are driving the growing obesity epidemic. Brain's reward system responsivity to food and monetary rewards in individuals with excessive weight (overweight and obese) versus normal weight controls, along with the relationship between this responsivity and body mass index (BMI) were tested. The sample comprised 21 adults with obesity (BMI > 30), 21 with overweight (BMI between 25 and 30), and 39 with normal weight (BMI < 25). Participants underwent a functional magnetic resonance imaging (fMRI) session while performing two tasks that involve the processing of food (Willing to Pay) and monetary rewards (Monetary Incentive Delay). Neural activations within the brain reward system were compared across the three groups. Curve fit analyses were conducted to establish the association between BMI and brain reward system's response. Individuals with obesity had greater food‐evoked responsivity in the dorsal and ventral striatum compared with overweight and normal weight groups. There was an inverted U‐shape association between BMI and monetary‐evoked responsivity in the ventral striatum, medial frontal cortex, and amygdala; that is, individuals with BMIs between 27 and 32 had greater responsivity to monetary stimuli. Obesity is associated with greater food‐evoked responsivity in the ventral and dorsal striatum, and overweight is associated with greater monetary‐evoked responsivity in the ventral striatum, the amygdala, and the medial frontal cortex. Findings suggest differential reactivity of the brain's reward system to food versus monetary rewards in obesity and overweight. Hum Brain Mapp 38:666–677, 2017. © 2016 Wiley Periodicals, Inc.     

Effects of gonadectomy and dihydrotestosterone on neuronal plasticity in motivation and reward related brain regions in the male rat

Gonadal hormones affect neuronal morphology to ultimately regulate behaviour. In female rats, oestradiol mediates spine plasticity in hypothalamic and limbic brain structures, contributing to long‐lasting effects on motivated behaviour. Parallel effects of androgens in male rats have not been extensively studied. Here, we investigated the effect of both castration and androgen replacement on spine plasticity in the nucleus accumbens shell and core (NAcSh and NAcC), caudate putamen (CPu), medial amygdala (MeA) and medial preoptic nucleus (MPN). Intact and castrated (gonadectomy [GDX]) male rats were treated with dihydrotestosterone (DHT, 1.5 mg) or vehicle (oil) in three experimental groups: intact‐oil, GDX‐oil and GDX‐DHT. Spine density and morphology, measured 24 hours after injection, were determined through three‐dimensional reconstruction of confocal z‐stacks of DiI‐labelled dendritic segments. We found that GDX decreased spine density in the MPN, which was rescued by DHT treatment. DHT also increased spine density in the MeA in GDX animals compared to intact oil‐treated animals. By contrast, DHT decreased spine density in the NAcSh compared to GDX males. No effect on spine density was observed in the NAcC or CPu. Spine length and spine head diameter were unaffected by GDX and DHT in the investigated brain regions. In addition, immunohistochemistry revealed that DHT treatment of GDX animals rapidly increased the number of cell bodies in the NAcSh positive for phosphorylated cAMP response‐element binding protein, a downstream messenger of the androgen receptor. These findings indicate that androgen signalling plays a role in the regulation of spine plasticity within neurocircuits involved in motivated behaviours.     

An obesity‐associated risk allele within the FTO gene affects human brain activity for areas important for emotion,impulse control and reward in response to food images

Understanding how genetics influences obesity, brain activity and eating behaviour will add important insight for developing strategies for weight‐loss treatment, as obesity may stem from different causes and as individual feeding behaviour may depend on genetic differences. To this end, we examined how an obesity risk allele for the FTO gene affects brain activity in response to food images of different caloric content via functional magnetic resonance imaging (fMRI). Thirty participants homozygous for the rs9939609 single nucleotide polymorphism were shown images of low‐ or high‐calorie food while brain activity was measured via fMRI. In a whole‐brain analysis, we found that people with the FTO risk allele genotype (AA) had increased activity compared with the non‐risk (TT) genotype in the posterior cingulate, cuneus, precuneus and putamen. Moreover, higher body mass index in the AA genotype was associated with reduced activity to food images in areas important for emotion (cingulate cortex), but also in areas important for impulse control (frontal gyri and lentiform nucleus). Lastly, we corroborate our findings with behavioural scales for the behavioural inhibition and activation systems. Our results suggest that the two genotypes are associated with differential neural processing of food images, which may influence weight status through diminished impulse control and reward processing.     

Apathy is related to reduced activation in cognitive control regions during set‐shifting

Apathy is a prominent and influential symptom in several neurological and psychiatric disorders, but it also occurs in the healthy population. It has considerable impact on daily life functioning, in clinical as well as healthy samples. Even though cognitive control is thought to be disrupted in people with apathy, the exact neural underpinnings of apathy remain unclear. Because flexible shifting between behaviors (set‐shifting) is crucial for goal‐directed behavior, disruptions in set‐shifting may underlie apathy. In this study, the neural correlates of apathy during set‐shifting were studied in 34 healthy participants with varying levels of apathy, measured by the Apathy Evaluation Scale. During functional MRI scanning participants performed a set‐shifting task, distinguishing between behavioral switches (a change in response to different stimuli), cognitive switches (a change in response rule), and salience decoupling (detecting a change in relevant stimuli). Regression analysis was used to assess the relationship between apathy and brain activation. Results showed that higher apathy scores were related to reduced activation in the medial superior frontal gyrus and cerebellum (Crus I/II) during cognitive set‐shifting, but not behavioral shifting and salience decoupling. No relationship between apathy and accuracy or response time was found. These results support the idea that alterations in the neural basis of cognitive control, especially cognitive set‐shifting, may contribute to apathy. Hum Brain Mapp 38:2722–2733, 2017. © 2017 Wiley Periodicals, Inc.     

Glucose administration enhances fMRI brain activation and connectivity related to episodic memory encoding for neutral and emotional stimuli

Glucose enhances memory in a variety of species. In humans, glucose administration enhances episodic memory encoding, although little is known regarding the neural mechanisms underlying these effects. Here we examined whether elevating blood glucose would enhance functional MRI (fMRI) activation and connectivity in brain regions associated with episodic memory encoding and whether these effects would differ depending on the emotional valence of the material. We used a double-blind, within-participants, crossover design in which either glucose (50 g) or a saccharin placebo were administered before scanning, on days approximately 1 week apart. We scanned healthy young male participants with fMRI as they viewed emotionally arousing negative pictures and emotionally neutral pictures, intermixed with baseline fixation. Free recall was tested at 5 min after scanning and again after 1 day. Glucose administration increased activation in brain regions associated with successful episodic memory encoding. Glucose also enhanced activation in regions whose activity was correlated with subsequent successful recall, including the hippocampus, prefrontal cortex, and other regions, and these effects differed for negative vs. neutral stimuli. Finally, glucose substantially increased functional connectivity between the hippocampus and amygdala and a network of regions previously implicated in successful episodic memory encoding. These findings fit with evidence from nonhuman animals indicating glucose modulates memory by selectively enhancing neural activity in brain regions engaged during memory tasks. Our results highlight the modulatory effects of glucose and the importance of examining both regional changes in activity and functional connectivity to fully characterize the effects of glucose on brain function and memory.     

Effect of brain structure and function on reward anticipation in children and adults with attention deficit hyperactivity disorder combined subtype

Attention deficit hyperactivity disorder (ADHD) is associated with decreased ventral-striatal responsiveness during reward anticipation. However, previous research mostly focused on adults with heterogeneous ADHD subtype and divers drug treatment status while studies in children with ADHD are sparse. Moreover, it remains unclear to what degree ADHD is characterized by a delay of normal brain structure or function maturation. We therefore attempt to determine whether results from structural and functional magnetic resonance imaging (fMRI) are associated with childhood and adult ADHD combined subtype (ADHD-CT). This study used fMRI to compare VS structure and function of 30 participants with ADHD-CT (16 adults, 14 children) and 30 controls (20 adults, 10 children), using a monetary incentive delay task. Joint analyses of structural and functional imaging data were conducted with Biological Parametric Mapping. Reward anticipation elicited decreased ventral-striatal responsiveness in adults but not in children with ADHD-CT. Children and adults with ADHD showed reduced ventral-striatal volume. Taking these gray matter differences into account, the results remained the same. These results suggest that decreased ventral-striatal responsiveness during reward anticipation is present in adults but not in children with ADHD-CT, irrespective of structural characteristics. The question arises whether ventral-striatal hypoactivity is an ADHD correlate that develops during the course of illness.     

Altered neural circuits related to sustained attention and executive control in children with ADHD: An event-related fMRI study

Objective

The aim of this study was to investigate the neural basis of sustained attention, executive processing, and cognitive control in children with attention deficit hyperactivity disorder (ADHD).

Methods

Event-related functional magnetic resonance imaging (fMRI) was used to compare brain activation of 28 medication-naïve children with ADHD aged 7–12 years and 31 healthy controls during a cued continuous performance task (AX-CPT) in three stimulus context conditions (Go, NoGo, Lure).

Results

The children with ADHD showed increased activation in the left middle frontal gyrus, bilateral middle temporal gyrus, left precuneus and right cerebellum posterior lobe under the Lure condition compared to the controls. In the Lure condition, in contrast to the NoGo condition, an increased activation in the left inferior frontal gyrus, right medial frontal gyrus and right inferior parietal gyrus was observed in ADHD children.

Conclusions

The results demonstrate that medication-naïve ADHD children show spatial and temporal abnormalities in neural activities involved in sustained attention and executive control.

Significance

These findings show that there are distinct alternations in neural circuits related to sustained attention and executive control in children with ADHD, and further improve our understanding of the neural substrates of cognitive impairment in children with ADHD.     

Overlapping patterns of brain activation to food and cocaine cues in cocaine abusers

Cocaine, through its activation of dopamine (DA) signaling, usurps pathways that process natural rewards. However, the extent to which there is overlap between the networks that process natural and drug rewards and whether DA signaling associated with cocaine abuse influences these networks have not been investigated in humans. We measured brain activation responses to food and cocaine cues with fMRI, and D2/D3 receptors in the striatum with [¹¹C]raclopride and Positron emission tomography in 20 active cocaine abusers. Compared to neutral cues, food and cocaine cues increasingly engaged cerebellum, orbitofrontal, inferior frontal, and premotor cortices and insula and disengaged cuneus and default mode network (DMN). These fMRI signals were proportional to striatal D2/D3 receptors. Surprisingly cocaine and food cues also deactivated ventral striatum and hypothalamus. Compared to food cues, cocaine cues produced lower activation in insula and postcentral gyrus, and less deactivation in hypothalamus and DMN regions. Activation in cortical regions and cerebellum increased in proportion to the valence of the cues, and activation to food cues in somatosensory and orbitofrontal cortices also increased in proportion to body mass. Longer exposure to cocaine was associated with lower activation to both cues in occipital cortex and cerebellum, which could reflect the decreases in D2/D3 receptors associated with chronicity. These findings show that cocaine cues activate similar, though not identical, pathways to those activated by food cues and that striatal D2/D3 receptors modulate these responses, suggesting that chronic cocaine exposure might influence brain sensitivity not just to drugs but also to food cues. Hum Brain Mapp, 36:120–136, 2015. © 2014 Wiley Periodicals, Inc .     

Intraindividual variability in children is related to informant ratings of attention and executive function

Objective: Attention and executive function (EF) deficits are ubiquitous in neurodevelopmental disorders including Attention Deficit/Hyperactivity Disorder (ADHD), as are high levels of intraindividual variability (IIV). Attention and EF are typically assessed using informant ratings and objective measures; however, discrepancies between different metrics often make it difficult to fully characterize a child’s attention capabilities, and IIV has been proposed as a potentially useful discriminator. Our objective was to explore the relationship between IIV, using the residualized intraindividual standard deviation (rISD) method, and informant ratings of attention and EF in a mixed pediatric sample, to determine the potential utility of IIV for aiding attention diagnostics. Another commonly used, though controversial, IIV indicator, the coefficient of variation (ICV), was calculated for comparison purposes.

Method: We assessed 51 children with varying degrees of attention and EF deficits. Measures included parent and teacher responses on the Comprehensive Executive Function Inventory (CEFI) and response times (RT) on a go/no-go task, which were used to estimate IIV.

Results: Mean RT, rISD, and ICV were significantly related to parent and teacher ratings of attention, though ICV showed a relatively weaker association. rISD also showed associations with parent ratings of working memory and self-monitoring, as well as teacher ratings of working memory.

Conclusion: The significant, and relatively stronger, relationship between rISD and parent and teacher ratings of attention supports the use of this metric, compared to mean RT and ICV. The rISD indicator of IIV thus shows potential utility as a unique and objective measure of attention in children across various neurodevelopmental disorders and, with additional research, may prove useful for diagnosis of attention problems.     

Traumatic brain injury and secondary attention-deficit/hyperactivity disorder in children and adolescents: the effect of reward on inhibitory control

Poor inhibitory control and abnormalities in responding to rewards are characteristic of the developmental or primary form of attention-deficit/hyperactivity disorder (P-ADHD). A secondary form of ADHD (S-ADHD) may occur as a consequence of childhood traumatic brain injury (TBI), but the similarities and differences between these two forms of ADHD have not been well characterized. To address these issues, we studied two inhibitory control tasks under different reward conditions in four groups of children and adolescents: TBI who did not exhibit S-ADHD, TBI who did exhibit S-ADHD, P-ADHD, and healthy controls. Participants with TBI exhibited poor cancellation inhibition relative to controls. Although reward facilitated both cancellation and restraint inhibition similarly across groups, poor performance persisted in the P-ADHD group, and participants with S-ADHD exhibited a selective deficit in cancellation inhibition.     

Task-specific hypoactivation in prefrontal and temporoparietal brain regions during motor inhibition and task switching in medication-naive children and adolescents with attention deficit hyperactivity disorder

OBJECTIVE: A relatively small number of functional imaging studies of attention deficit hyperactivity disorder (ADHD) have shown abnormal prefrontal and striatal brain activation during tasks of motor response inhibition. However, the potential confound of previous medication exposure has not yet been addressed, and no functional imaging study exists to date on medication-naive children and adolescents with ADHD. The aim of this study was to investigate the neural substrates of a range of motor and cognitive inhibitory functions in a relatively large group of children and adolescents with ADHD who had never previously been exposed to medication. METHOD: Nineteen boys with ADHD and 27 healthy age- and IQ-matched boys underwent functional MRI to compare brain activation during performance of tasks that assessed motor response inhibition (go/no go task), cognitive interference inhibition (motor Stroop task), and cognitive flexibility (switch task). RESULTS: Boys with ADHD showed decreased activation in the left rostral mesial frontal cortex during the go/no go task and decreased activation in the bilateral prefrontal and temporal lobes and right parietal lobe during the switch task. No significant group differences were observed during motor Stroop task performance. CONCLUSION: Abnormal brain activation was observed in medication-naive children and adolescents with ADHD during tasks involving motor inhibition and task switching, suggesting that hypoactivation in this patient group is unrelated to long-term stimulant exposure. Furthermore, functional abnormalities are task-specific and extend from frontostriatal to parietal and temporal cortices.     

Is sustained attention deficit related to subclinical obsessive thoughts in children and adolescents with ADHD?

Abstract

Background: Thought content and its impact on sustained attention in individuals with attention deficit hyperactivity disorder (ADHD) are topics of growing interest in literature.

Objective: We hypothesised that subclinical obsessive thoughts may be correlated with attention lapses in individuals with ADHD.

Method: Thirty children diagnosed with ADHD participated in the study and their level of subclinical obsessive thoughts, attention, and executive function were measured using Children Yale-Brown Obsessive Scale and Conners’ Continuous Performance Test II.

Results: No significant correlation between sustained attention impairment and the level of obsessive thoughts in patients with ADHD was found. Nevertheless, patients with ADHD with subclinical obsessive thoughts showed more commission errors than those without (W?=?51.5; p?=?0.02).

Conclusion: The nature of thought content in individuals with ADHD should be linked to executive dysfunction rather than attentional impairment. This could be of importance in the therapeutic strategy choice, addressing the importance of executive function remediation in the specific context of subclinical obsessive thoughts.

• Key points

• ?Patients with ADHD, without OCD or ASD comorbidity, still present subclinical obsessive thoughts (36% of our sample). ??Subclinical obsessive thoughts could be a part of thought content in patients with ADHD.

• ???Subclinical obsessive thoughts as measured by the CPT-II are not correlated with attention function in patients with ADHD.

• ???ADHD patients with subclinical obsessive symptoms present more impairment in response inhibition than the ones without.

• ???Results on subclinical obsessive thoughts are similar to those on another type of thought content called ‘mind wandering’.

• ???A clinical improvement strategy for patients with ADHD could be using executive function remediation rather than classical attention function remediation, according to both to our and previous results.

     

Factors related to diagnostic persistence of attention deficit/hyperactivity disorder in Turkish children and adolescents

Objective: Attention-deficit/hyperactivity disorder (ADHD) is one of the most frequently occurring mental disorders in children and adolescents. The purpose of this study was to determine diagnostic persistence three years after the first clinical evaluation and to investigate the factors relating to diagnostic persistence in children and adolescents with ADHD. Methods: The study included 183 children and adolescents who were evaluated in the first admission. Of 183 children and adolescents, 142 children and adolescents were evaluated in the second admission and only the data of 142 children and adolescents were analysed in the study. Diagnostic persistence was defined as having met the full criteria for ADHD on second evaluation. Symptom severity of ADHD was determined using the Turgay DSM-IV-based Child and Adolescent Behavior Disorders Screening and Rating Scale-Parents Form (T-DSM-IV-S). Intelligence level was assessed through the Wechsler Intelligence Scale for Children-Revised. Results: Of the children included in the study, 77.5% (n?=?110) were determined to have ADHD diagnostic persistence. Low intelligence levels, younger age and higher T-DSM-IV-S inattention and conduct disorder scores were associated with diagnostic persistence. ADHD diagnosis in children and adolescents tends to continue at high rates. Conclusions: Determination of the risks related to ADHD diagnostic persistence may contribute to improved treatment planning and interventions.     

Synaptic proteins in frontal and control brain regions of rats after exposure to spatial problems

Synaptic proteins D1, D2, D3, synaptin and 14-3-2, as well as the glial protein glutamine synthetase, were measured by crossed immunoelectrophoresis in the anteromedial (prefrontal) cortex, occipital (visual) cortex and the anterior and posterior parts of the neostriatum of rats. The 3 experimental groups consisted of rats trained to criterion in a spatial delayed alternation, those run as yoked controls and, finally, rats kept in individual cages and not subjected to any training. Statistical analysis showed that two variables: behavioral procedures and brain regions, had a significant effect. Their interaction was also significant. Further analysis revealed that only in the prefrontal cortex of the yoked control animals was there a significant decrease of the synaptic membrane proteins D1, D2 and D3. Thus, particular behavioral treatment seems capable of affecting synapses in a specific ‘association’ cortical area. The change is more easily related to the amount of ‘work’ than to formation of ‘memory trace’ within the critical area.     

Suicide attempts and impulse control disorder are related to low cerebrospinal fluid 5-HIAA in mentally disordered violent offenders

OBJECTIVE: The aim of this study was to investigate the relationship between low cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA) and aggressive acts in mentally disordered violent offenders. METHOD: CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid and 4-hydroxy-3-methoxyphenyl glycol were measured in 35 drug-free men convicted of homicide and currently undergoing forensic psychiatric investigation in a high security hospital. RESULTS: The mean metabolite concentrations in the homicide offenders did not differ from those of age- and body-height matched male control subjects. One-third of the murderers had made one or several suicide attempts, and their mean concentration of spinal fluid 5-HIAA was significantly lower than that of the remaining murderers. Subjects with impulse control disorder also had lower mean CSF 5-HIAA. A consistent pattern of higher CSF 5-HIAA in subjects with more self-reported anxiety traits was observed. CONCLUSION: The association between serotonin and suicidal behaviour holds for yet another subject group. Determining CSF 5-HIAA might be worth while in the routine assessment of psychiatrically ill homicide offenders.     

Abnormal brain activity related to performance monitoring and error detection in children with ADHD

Brain electrical activity associated with inhibitory control was recorded in ten ADHD and ten healthy children using high density event related potentials (ERPs) during the Stop Signal Task (SST). SST is a two-choice reaction time (RT) paradigm, in which subjects are required, on 25% of the trials, to withdraw their response upon presentation of a "Stop Signal". In the healthy children, the ERP evoked by the Stop Signal differed for successful inhibitions (SI) compared to failed inhibitions (FI), with greater amplitude of a positive wave peaking around 320 msec over anterior medial frontal scalp (P3a). Such success-related P3a activity was significantly reduced in amplitude in the ADHD group. In addition, the error related negativity (ERN), a sharp negative wave that is present selectively on error trials in choice RT experiments, peaking 100 ms after motor onset, and distributed over anterior medial frontal scalp, was also markedly reduced in the ADHD group. The scalp distribution of the group differences in P3a and the ERN is consistent with a reduction of activity of sources in dorsal anterior cingulate cortex (dACC), suggesting a global deficit in cognitive control operations subserved by dACC in ADHD.     

On-line psychophysical data acquisition and event-related fMRI protocol optimized for the investigation of brain activation in response to gustatory stimuli

An experimental method for event-related functional magnetic resonance imaging that allows for the presentation of several chemosensory stimuli in the oral cavity during the same run, the collection of psychophysical measures (intensity or pleasantness) during the presentation of the stimuli, and the analysis of the data in an event-related fashion are described. The automatic pumps used to present taste stimuli allowed for multiple tastes to be delivered in small amounts under computer control. Psychophysical ratings of pleasantness or intensity were collected after each presentation of a taste stimulus and water, with the general labeled magnitude scale, using a joystick that controlled the movement of an arrow on the visual display. Performing these cognitive tasks required that the participant remained focused, and aided in the interpretation of the data collected. The perceived pleasantness differed across stimuli for all conditions; however, pleasantness ratings for the same stimulus displayed consistency, over the duration of the run and before each scan on separate days. Activation in response to sucrose and caffeine while the participant rated pleasantness was found in the insula, frontal operculum, rolandic operculum and orbitofrontal cortex which is consistent with previous taste fMRI studies.