ADHD

ADHD

• To characterize the symptoms and demographics of ADHD
• To evaluate theories of cognitive deficits underlying ADHD
• To understand the heterogeneity in ADHD
• To describe the neurological basis of ADHD
• To discuss the link between the neurobiology and cognitive bases of ADHD
• - How could existing cognitive research in ADHD be
• used to improve the specificity of diagnosis for the disorder (i.e.,
• identifying who has the disorder)?
• -Are non- pharmacological interventions for ADHD successful? Evaluate the evidence
• -
• How well do neurobiological differences map onto
• the cognitive deficits seen in ADHD?
• Introduction to ADHD
• Cognitive theories of ADHD
• Neurobiological basis of ADHD

Introduction to ADHD

• Concept of ADHD first discovered by Heinrich Hoffmann, who was a german physician who first observed behavior in children who depicted what is now known as ADHD symptoms. An Idea that has been around for a while, perhaps not as well understood in terms of causes
• DSM-V Criteria - If the child is diagnosed with ADHD they have to exhibit 6 symtpoms of inattention/hyperactivity or 3 for each of these.
• Persistent over time and setting e.g. both at home and at school.
• The symptoms should lead to significant impairment in social, academic circumstances.
• The symptoms cannot be explained by other clinical disorders, because some of the symptoms can overlap it is important for clinicians that they are not mis-diagnosing children if they have something else going on.
• Inattention: fails to give close attention to details and may struggle with following through on activities etc.
• Hyperactivity: Fidget, leave seats, excessive talking, some
• Affects an individuals ability to control attention and behavior in an optimal and adaptive manner.
• Chronic, debilitating condition
• Three subtypes of ADHD:
• 1. Predominantly hyperactive-impulsive
• 2. Predominantly Inattentive type
• 3. Combined type.
• Hyperactive- Impulsive: Feeling restless, Fidgety, Squirming with hands or feet.
• Inattention: Becoming easily distracted by irrelevant sights and sounds. Failing to pay attention to details and making careless mistakes.

Co-Morbidity between ADHD

• ADHD tends to co-occur with other developmental and psychiatric disorders at high rates.
• Most of the negative outcomes for ADHD are exacerbated by the presence of co-morbid conditions, especially aggression and conduct problems
• Estimate for comorbidities in childhood are approx. 60% for oppositional defiant disorders, 20 % for conduct disorder, 25% for mood disorders, 25% for anxiety disorder, 30% for learning disorders such as dyslexia and somewhat higher for developmental coordination disorder.

Definition and Demographics

• Two different components to the disorder and produces three different subtypes
• 1. Inattention
• 2. Hyperactivity/Impulsivity: less commonly diagnosed on its own.
• 3. Combination of both: most common
• Peak onset between the age of 3 and 4- often when children are pulled into more structural environments is when it gets more noticed
• More commonly noted in males than females, particularly for hyperactivity/impulsivity type
• Affects 3%-5%
• Half of the children who have ADHD have another diagnosis of some sort e.g. autism, learning difficulties, dyslexia.
• Particularly in adulthood can often develop a dependency of substance abuse.
• More accident prone: not planning and sleep problems: not being able to settle
• Persists into individuals for around 50%-60% and develops into adulthood for around 30%-50%

Subtypes of ADHD

• Diamond (2005)- hyperactivity is a separate disorder from ADHD purely inattentive (ADD)
• Different neurobiological basis
• Mixed evidence of whether there really are sub-types
• There are three core symptoms of ADHD of the combined type: Inattention, hyperactivity, and impulsiveness.
• All the research on ADHD has focused on children who show the more noticeable symptoms that get the children noticed and diagnosed as having ADHD.
• In relation to explaining the problems of hyperactivity and impulsiveness seen in children with ADHD, there has been a strong consensus that this reflects a problem of behavioral inhibition/ executive control
• There is a degree of circularity in this view since ADHD is diagnosed when there are signs that an individual has difficult with self regulation in a variety of settings and so behaves in an uninhibited way.
• In order to understand the causes of ADHD it is important to operationalize the term "behavioral inhibition" and to consider the development of executive control in the typically developing child.

Genetics

• Quantitative Genetics
• ADHD is considered to be one of the most highly heritable of psychiatric disorders
• Family studies report a high incidence of ADHD among both first and second degree relatives of probands (children diagnosed as having ADHD) and the rates of ADHD are also greater among biological relations than among adoptive relatives of children with ADHD
• Concordance rates are significanlty higher for MZ (58-82%) than DZ pairs (31-38%), providing evidence that ADHD is heritable.
• In addition studies the fact that MZ concordance was less that 100% in all studies, suggest that environmental influences also play a role in the etiology of ADHD.
• Estimates heritabiliy differ depending on who is the informant regarding behavioral symptoms and what instruments are used.
• Levy et al. (1996): used data from a questionnaire based on the DSM-II and completed by mothers of an Australian sample of probands (kids with Adhd) and found concordance rates of .82 in MZ and .38 in DZ twins.
• Goodman et al. (1989) reported wide ranging concordance rates from .48 to .79 in MZ and .08 and .44 in DZ twins in a uk sample.

Molecular genetic approaches

• Most molecular genetic studies of ADHD have focused on genes that operate to influence the functioning of dopamine systems in the brain.
• These genes are of specific interest because drugs such as Ritalin that reduce the reuptake of dopamine systems are known to be effective treatments for ADHD.
• How do we get from understanding genetics to the behavioral symptoms
• Consider various stages in between that help us understand how we get from genetics to behavior
• Endophenotype: do tests that help us find cognitive markers. Through that identify brain areas etc.
• Work backwards to then say, so if we know that children who exhibit
• symptoms of ADHD and show certain behaviors of psychophysical tests.
• Which genes are involved with those tests?
• Endophenotypes
• There is an increasing interest in an alternative approach, namely the identification of endophenotypes.
• Can be defined as heritable traits that index an individuals liability to develop or manifest a given disease
• Possible endophenotypes of ADHD include working memory, inhibition, temporal processing and a shortend delay gradient, all of which show some genetic influence and partial familial overlap, especially inhibition and processing speed.

Social and Environmental Risk factors

• Majority of research suggests that the effects of individual gene products on ADHD are small and that genes invovled in the transmission of ADHD are probably also involved in the transmission of other disorders
• Environmental factors that have been associated with ADHD include prenatal factors such as maternal smoking, and exposure to maternal alcohol consumption
• Low birth-weight, severe early deprivation such as major disruption of attachment
• McCann et al. (2007) artifiical colors and preservatives added to fruit drink led to increased hyperactivity in 3-8/9 year olds in the general population
• Of course, both the active and passive correlation between genetic and environmental factors can influence behavioral outcomes in ADHD.
• Parents of children with ADHD will often themselves exhibit continuing patterns of hyperactivity and impulsivity that provide poor models for the development of organization and self-management skills.
• Alcohol and nicotine used by mother during pregnancy.
• Complications in delivery of the baby
• Low birth weight or premature weight
• Complex picture from a pathway involving genes and the environment

Cognitive Theories of ADHD

• Executive Function Tasks
• A wide range of tasks has been used to asses executive function in children and adults
• Among the most common of these are planning tasks such as the tower of hanoi and tasks tapping working memory and memory updating.
• Other tasks tap the ability to attend selectively to a given set of cues, whilst ignoring or suppressing extraneous information - the most common used task tapping such interference control is the Stroop task.
• Participants have to name the color of the ink of a set of color-words e.g. red printed in blue, and to do so, they have to suppress the automatic tendency to respond with the name of the printed word.

Theory 1. Executive Function

• Inhibition: main executive skills - control response and be able to attend to one item by ignoring other. Stroop task is one of the more cognitive tasks measuring inhibition
• Respond to one stimuli by ignoring aspect of another
• Could be a dominant candidate: one of the most established explanations of all the 4 theories.
• Barkley (1997) suggested that weak inhibition can lead to deficits in other areas e.g. 1. Working Memory (ability to hold things in mind) 2. Self-regulation 3. internalization of speech 4. Reconstitution
• They don't tend to delay their response. Not much holding back and planning for future behaviour. Respond innately to any sensory or environmental stimuli that you are faced with.
• Nigg (2005) reviewed a large number of studies that have looked at executive tasks in children with ADHD to see what aspects of EF is affected the most. Calculated effect size: how strong the difference is. How strong of a difference was there between the groups.
• According to Barkley's model (1997), ADHD can be traced to a fundamental disorder of behavioral inhibition: an ability to inhibit a prepotent response to stop responding and to control interference.
• The task that has been used most widely to test this idea is the stroop-signal task. In this task, the child performs a primary go task, whilst monitoring for a stop signal that indicates the response to the primary task should be inhibited.
• For a child such ability may be required when they are engaged in games of chase or when the school bell rings and the child is required to stand still.
• In the stop -signal paradigm, the primary task is usually a visual choice reaction time task. e..g pressing the x button on a keyboard when an x is presented. On a randomly occurring proportion of trials, the primary task stimulus is followed by a stop signal, which is the cue to inhibit the planned response to the primary task or "go signal"
• A study by Solanto et al. 2001 looked at successful stop trials across blocks of trials in children with ADHD and controls.

Studies on response inhibition

• Solanto et al. 2001
• Children with ADHD typically showed longer stop-signal reaction times than TD children.
• Often children with ADHD make a lower proportion of successfully inhibited responses.
• Rubia et al. (2001)
• Compared a clinical sample of 56 children with ADHD aged 7-15 years with both a psychiatric control group of 16 children and a group of 23 TD children on a range of tasks designed to asses impulsivity in the broadest sense
• Three groups were matched for age and IQ
• The test battery consisted of the strop-signal task and a simpler no/no-go task- in which a motor response had to be executed or inhibited depending on whether an image of an aeroplane appeared on the screen.
• In the tasks measuring inhibition, group differences in the probability of inhibition were significant, with ADHD children showing less inhibition and more error prone than the TD controls- but not the children in the psychiatric control group.
• Shows that inhibition problems are not just related to ADHD.
• However a measure of standard deviation shows that there were substantial effect sizes for group differences and the ADHD group was three times more variable compared to controls.

Nigg et al. (2005)

• Looked at which EF was most impaired
• Strongest effect size was found in spatial working memory and response suppression task e.g. stroop task.
• Verbal working memory: string of different animals e.g. less difficult to do
• Particularly difficult with response suppression: withholding response to a target that you shouldn't respond to
• Martinussen et al. 2005
• Report a meta-analysis of studies of working memory deficits in children with ADHD
• They report that chidlren with ADHD show deficits on spatial memory storage tasks (average d: 0.85) and spatial central executive tasks (average d: 1.06) that are greater than the deficits found on comparable verbal storage tasks or verbal central executive tasks.
• These deficits in working memory could not be accounted for by differences in measures of language skill or general IQ between the children with ADHD and controls.
• These results suggest that deficits on working memory tasks are an area of difficulty for children with ADHD:
• Executive impairment seems broad as a potential explanation for the deficits observed in children with ADHD.

Theory 2. Reward Processing Theory

• Motivational Theories: Possible abnormalities in system responsible for motivation or arousal as explanation for ADHD. According to such theories, altered stated of arousal or motivation leads to a different response pattern in children with ADHD.
• Alternative explanation - difficulties in processing reward. Causing inattention especially
• Children with ADHD may show an aversion to the delay of rewards.
• Idea is that anyone would accept a lower amount than having to wait a long time. Those with ADHD will always go much lower, they will accept the now much earlier than take the delay and wait longer. e.g. Marshmellow task.
• Children with ADHD do not like to wait and they cannot defer gratification; hence they present as impulsive in cognitive style and cannot work effectively over extended periods of time when sustained attention is required.
• Brain Netword involved with reward processing
• Orbitfrontal Cortext
• Ventromedial prefrontal cortext
• Anterior Cingulate Cortex
• Striatum
• Amygdala
• Key areas involved with the brain
• These areas respond to any types of reward in the environment, whether its food, social reward, cultural reward etc.

Theory 2: Study

• Kuntsi et al. (2001) tested delay aversion using a computer-presented space game.
• The child had to make a choice between an immediate reward: one point, involving a 2s prereward delay, and a larger delayed reward (two points, involving a 30s pre-reward delay.
• Consistent with earlier findings, children with ADHD chose the larger reward significantly less often than controls and this difference remained significant after IQ was controlled for.
• However, when symptoms of co-morbid conduct disorder were controlled for, the main effect of group was no longer significant
• Since few studies examining at reward processing control for co-morbidity, it is hard to say to what extent the delay aversion impairment is due to ADHD.

Theory 3: Timing

• Less evidence for this theory: not as well understood and out of fashion now
• Basic idea was that if individuals with ADHD have a timing issue in gaging how much time have past, this could cause problems.
• Poor understanding of how much time has past could lead them to be quite bored etc.
• Evidence: Toplak et al. (2006)
• A) Get played a tone followed by another tone. Have to say whether the second beep was longer, shorter or the same length as the first one.
• B) A tone played, and have to replicate how long you think the sound occurred for.
• C) Tapping in time to intervals with a metronome
• D) Anticipation task: Child giving an indication of how much time has occurred: press the button when three seconds have passed.
• Reasonable evidence to suggest that children did have difficulties with timing. Particularly for the first 3 tasks.
• Timing perception is also something that gets picked up on the dyslexia spectrum.

Theory 4: RT variability in ADHD

• RT variability may underpin all the other cognitive difficulties aswell e.g. executive dysfunction difficulties
• Not separate
• Identifying this may give rise to the other deficits observed aswell
• The essence of the theory suggest that children with ADHD will have poorer intra-attentional, which results in them being quite variable in their consistency in responding. Particularly in response time
• Task: showing children pictures on a screen and asking them to push a button when they see the certain picture.
• Normal behavior: consistent and average response time
• Children with ADHD have huge variabiliy- idea is that it could be that there are lapses of attention that occur, or difficulty in maintaining information that causes variability.
• More of an observation rather than a cause: more likely to be a brain mechanism that causes this.
• On RT tasks you often get something skewed.
• Research compares controls and ADHD individuals.
• There is a different way of thinking about cognitive problems in children with ADHD, which is in terms of variability of performance. In this view children with ADHD can perform cognitive functions normally, it is just that their performance is highly variable.
• Some of the evidence already considered is consistent with this view, e.g. Kuntsi et al. (2001) found that the variability of RTs in children with ADHD was larger than for control children.

RT variability

• Epstein et al. (2011)
• Looked at those who had combined ADHD and ADHD-inattentive and controls- completed 5 different RT tasks assessing a variety of cognitive abilities.
• Multiple indicators of RT variability were measured.
• Exponential component e.g. Tau was the only RT variability indicator that identified group differences across all tasks.
• Children with ADHD showed greater RT variability compared to controls across tasks.
• Suggests that an increased RT variability is a robust phenomenon in children with ADHD
• More recently Castellanos et al. 2005 suggested that ADHD might be conceived as reflecting variable performance.
• Presents analysis of RT data from ADHD and control children.
• We first identify five key research questions and methodologic issues.
• For illustration, we examine the periodic structure of Eriksen Flanker
• task reaction time (RT) data obtained from 24 boys with ADHD and 18
• age-matched comparison boys.
• Reaction time variability in ADHD differed
• quantitatively from control subjects
• For now it seems more of an observation of behavior than an actual cause of ADHD or an explanation for the symptoms of ADHD
• It is too early to judge the likely generality or importance of intrachild variations in performance as an explanation for the cognitive deficits seen in children with ADHD.
• However- seems interesting avenue for future

Executive Function as core explanation

• Looking back at study by Nigg et al. 2005
• Looked at different executive measures and looked at percentage beyond 90th percentile of performance in control participants. Finding those who had performed really low and compared to control participants. If you took all the performance on the control participants and the bottom 10% of the control group is saying: how many children with ADHD performed at 10 percent of the control group or below.
• Performance suggests that there is a lot of overlap with controls and diagnosed ADHD, still performing similarly to control participants.
• Shows that not all children with ADHD have a deficit in executive functioning. Less than half of the individuals will show a difficulty substantially lower than the control group.
• If it is a core impairment then we should get an impairment in all children with ADHD.
• Deficit in executive functioning in ADHD is not universal

Theories as core explanations

• Can these theories be thought of as core explanation?
• Are any of these main deficits that account for all the symptoms?
• One of the issues that have alluded is perfomrance in children with ADHD is variable; coupled with this they display slow speeds of processing.
• This could potentially be explained either in terms of cognitive deficiencies in executive control, or by recourse to suboptimal levels of arousal and lack of consistent effort
• Sergeant et al. (1998) have proposed that the overall efficiency of information processing is determined by the interaction of computational resources e.g. processing and storage capacity, state factors such as motivation and arousal, and executive functions.
• From this perspective a single deficit model of ADHD is not sufficient because they fail to take into account the role of task parameters in the determination of performance.
• For example the rate of stimulus presentation alters the energic state of an individual and thereby affects performance. In this way, fast rates of stimulus presentation can lead to overarousal, with fast inaccurate responding as a consequence.
• Slow rates of stimulus presentation may lead to underarousal and slow, inaccurate performance.
• Children with ADHD appear to have difficulty in modulating their energic state such that they generally perform more poorly at slow rates of presentation but more normally with fast rates of stimulus presentation.
• They may have difficulty in maintaining an optimal arousal state with consequent difficulties for the organization of motor responses.
• Sergeant et al. (1998) uses the term cognitive energic model to explain the variable profile of arousal and responding in ADHD.

Cognitive-Energetic Model

• Bottom Up / Top- Down Models
• Model to try and capture the variability in ADHD has been the cognitive energetic model and this tries to identify and suggest that there may be a lower level physiological cause to the condition, which could be having a knock-on leading to secondary difficulties e.g. executive function
• Suggests three levels:
• 1. Computational Model: basic level of encoding sensory and motor
• 2. Refers to the arousal, effort and activation of that information. Arousal is particularly important: stimuli is coming through at a certain intensity then arousal may be very high or low. Arousal regulation can create variable performance.
• 3. Basic low physiological difficulties can impact monitoring and evaluation.
• Idea specifies that bottom up factors could be driving secondary difficulties. d
• How do we identify which cognitive processes may be core deficits in ADHD?
• In order to say whether a certain difficulty is a core impairment or feature or marker of ADHD it needs to have certain criteria.
• Asked to write an essay on "what are the core explanations of understanding ADHD" "Evaluate the core theories" explore how each of the explanations meet these criteria:
• 1. Co-occur with the disorder: e.g. Reaction Time: The greater reaction time variability should result in greater symptoms of ADHD.
• 2. Should be heritable. i.e. look at twins, family unit.
• 3. Should show familial susceptibility
• Determine to what extent the cognitive impairments discussed meet these criteria
• If

Triple Route Model

• Sonuga Barke et al. (2010)
• Multiple cognitive causes and that they carried out a variety of tasks that tap into 3 different domains including: 1. Inhibitory Control, 2. Delay Aversion, 3. Temporal Processing in participants with and without ADHD as well as siblings who had risk factors of ADHD.
• Importantly: Only 71% of participants with ADHD displayed some sort of neuro-psychological deficit
• 1/3rd of participants that showed no problems in delay, timing or inhibition.
• 1/3rd of participants that show no cognitive impairment
• Of those only 70% showed a deficit in one of those areas.
• 1/3rd showed no core impairment and those who did only had a problem in one of the areas.
• The group is very variable- completely different causes that have different underlying reasons.
• Hard to say that there is single cognitive explanation
• Timing was associated with reading problems
• Delay problems were associated with low IQ and reading problems.
• Criticism: Sample used was small for the examination of subgroups. Second measurement of working memory and intelligence was limited.
• Notes on paper
• Neuropsychological studies of ADHD implicate a broad range of processes. These include executive function, for example inhibitory and working memory deficits, non-executive deficits for example perception, memory, timing and alterations in motivational processes.
• This study adopted a multivariate methodology, with three tasks chosen for each neuropsychological domain to improve measurement reliability and allow the underlying latent structure of neuropsychological deficits to be explored
• 71 families with an ADHD child participated
• Data provided first evidence that timing, inhibition and delay deficits in ADHD are dissociable from each other and that substantial subgroups of patients are affected in only one domain
• The strongest evidence for familial effects came from inhibition and timing. Sibilings of probands with impairment in one of these domain also tended only to have problems in these domains.

ADHD: Different subtypes?

• Different Etiologies for Inattention and Hyperactivity?
• DSM-IV distinguishes between two dimensions of impairment that occur in children with ADHD: inattention and hyperactivity/Impuslivity.
• This gives rise to the 3 subtypes and need to consider the extent to which these symptoms may depend upon different underlying impairments at the biological and cognitive level of explanation.
• Chhabildas et al. (2001) compared the neuropsychological profiles of children with ADHD diagnosed according to the DSM-IV criteria as predominantly hyperactiviity-impuslivity, inattentive or the combined subtype, recruited from colorado twin study.
• They complteted tests of spelling, reading and IQ and performance on two tests of inhibition and two tests of processing speed and a measure of sustained attention.
• The profiles of impairments differed across tasks.
• The inattentive group and combined subtype group perfomed similar to one another and less well than controls whereas the Hyperactive/Impuslivity subgroup had less difficulty overall on the cogniive tasks.
• Children who showed symptoms of inattention showed a range of cognitive impairments that are typical of children with ADHD, whereas children from the Hyperactive/Impuslivity subgroup generally performed normally on these cog. processing tasks.
• suggests that a number of cognitive impairments that are said to characterise children with ADHD may actually be associated with inattention but not hyperactivity.
• Sample size was predominantely HI group was small and samples studied here were relatively old (10-12), which means patterns need to be replicated.

Summary of cognitive theories

• Executive Function i.e. inhibition and working memory
• Reward Processing i.e. motivational problems
• Timing
• Reaction Time variability i.e. slower processing
• Large heterogeneity: dont show the exact same profile
• Modern theories propose a model with multiple causal pathways.
• Which cognitive factors are causal factor? Is it possible to come up with a unitary explanation when there is so much heterogeneity.

Neurobiological Basis of ADHD

• Delayed Brain maturation
• Dopamine Dysregulation
• Impaired connectivity
• Etiology of ADHD
• Research on the biological bases of ADHD has arguably been more influential in helping to understand the disorder than for the other disorders considered so far.
• Research in this area has involve psychopharmacology (drug treatments and their mode of action on psychological and brain processes), genetics, and studies of brain structure and function.
• Typical executive function development
• Executive function in ADHD
• Sensory/reward theories

Neurophysiologic Theories of ADHD

• Neurobiological theories of ADHD have centered on two common, but not mutually exclusive models.
• 1. Emphasizes top-down, controlled processing problems, such as those associated with cognitive control or executive functioning
• 2. Another model emphasized bottom-up, motivational and incentive reward response.
• While consensus is yet to be reached on the core neural pathways that lead to the disorder, there exist several lines of evidence that support both of these models and suggest both types of psycho-biological systems are involved in ADHD.

Psychopharmacology of ADHD

• Research on ADHD has attracted the interest of psychopharmacologists far more than any more disorder
• This interest follows from the idea that ADHD reflects impairments in the regulation of the brains neurotransmitter system and evidence that certain drug treatments can help to reduce the symptoms of ADHD.
• The PFC appears to play a critical role in guiding attention and inhibiting distracting stimuli.
• Either too little or too much stimulation of the DA receptors impairs working memory function in rats and monkeys, with performance following a U-shape curve in response to dosage of dopamine antagonists.
• Interest in the possible role of the catecholames in ADHD was stimulated by the observation that treatment with drugs that affect catecholamine transmission improved the symptoms of children with ADHD e.g. ritalin, which blocks both dopamine and norepinphrine transporters and improves the symptoms of ADHD. (Arnsten & LI, 2005)

Pharmacology

• Another way in which we can understand the biological underpinnings better, is to explore and understand better how some individuals may respond to various pharmacological treatments.
• One type of treatment that has a positive response in individuals with ADHD is Ritalin: These drugs are used to stimulate and regulate dopamine within the brain.
• Drug regulates dopamine has positive effects of ADHD, and therefore suggests that there may be biological differences in the dopamine system and how the brain regulates it.
• Durston & Konrad, 2007
• Dopamine Dysregulation Hypothesis of ADHD
• Hypodomanigergic state in the prefrontal cortex
• Idea is that ADHD symptoms which are results of dopamine disregualtion are due to two different things happening:
• 1. Pre-Frontal Cortex: Too low levels of dopamine
• 2. Striatum: Too low levels of dopamine
• The drugs help increase release of dopamine and increase the levels of dopamine in the prefrontal cortex, which helps to deal with the inattentive problems.
• Ritalin can also affect the reuptake of dopamine in the brain by inhibiting the reuptake of dopamine
• Ritalin helps for both.
• Striatum: Hyperactivity
• PFC: Inattention and lack of cognitive control
• Ritalin shows a nice clear way of dealing with both parts of the condition

Pharmacology and ADHD

• Critical view against the dopaminergic hypothesis of attention-deficit/hyperactivity disorders needs re-examining.
• People are still uncertain about it.
• Look closer to see what is happening
• Dopaminergic dysfunction has received most attention but does not mean that other neurotransmitters have not been associated with ADHD.
• e.g. Norepinephrine and noreadrenaline
• Serotonin
• Gonon, 2009
• Although psychostimulants alleviate the core symptoms of adhd, recent studies confirm their impact on the long-term outcomes of ADHD children is null.
• Shaw et al. showed that, in contrast to other neuro.developmental disorders such as austims, ADHD is characterized by delay rather than deviance in cortical maturation.
• Main drawback of the dopamine-deficit theory is that it gives scientific credence to a view that facros psycho-stimulant medication over other meidal, psychological and social approaches to ADHD treatment.
• Recent evidence-based studies question the view that psychostimulant medication has long-term beneficial effects of ADHD and point out that the interest of psychosical treatments

Delayed Brain Maturation Hypothesis

• Difference in grey matter in the brain, specifically a delayed maturation in its grey matter development
• Within studies that have been carried out shows that this develops in typical children and that there is a delay in great matter within children with ADHD
• When studies have been carried out they looked at the cortical thickness of the brain in groups of ADHD and TD
• ADHD propotioanlly have a reduced amount of grey matter. This reduction is particularly notable in the prefrontal cortex- which is not fully formed and developed in young children but this seems to be significantly marked in those with ADHD
• The brain may have delayed developing grey matter.
• Shaw et al. 2007
• Controversy over the nature of the disturbance in brain development that underpins ADHD
• Unclear whether the disorder results from a delay in brain maturation or whether it represents a complete deviation from the template of typical development.
• Using computational neuroanatomic techniques, estimated cortical thickness at cerebal points from scans acquired from 223 children with ADHD and 223 TD controls.
• With the sample size it was possible to define the growth trajectory of each cortical point, delineating a phase of childhood increase followed by adolscent decrease in cortical thickness.
• Found maturation to progress in a similar manner regionally in both groups.
• There was a marked delay in ADHD in attaining peak thickness throughout most of the cerebrum: the median age by which 50% of the cortical points attained peak thickness for this group was 10.5 yrs. compared to 7.5 years in TD. Delay was most prominent in prefrontal regions, important for control of cognitive processes including attention and motor planning.

Evidence for delayed maturation hypoth.

• Rubia 2007
• Importantly is that it is found to be specific to ADHD and not found in other developmental disorders
• One may question if they had delayed in general.
• Suggesting it is unique in ADHD and has not been found in other developmental disorders.
• This delay in brain maturation, it does make sense as children with ADHD mimic behavior in younger children
• Delayed development.
• Acting like a younger child that has less ability to regulate behavior.

White matter

• Various anatomic brain abnormalities have been reported for ADHD with
• varying methods, small samples, cross-sectional designs and without
• accounting for stimulant drug exposure
• White matter is about connections between the different parts of the brain
• 152 ADHD children and 139 control children
• Reduction in brain volume overall, particularly in white matter areas
• Particularly in the frontal areas, parietal and temporal
• It is also found in other sub-cortical areas of the brain. Not necessarily restricted to frontal areas.
• Developmental
• trajectories for all structures, except caudate, remain roughly
• parallel for patients and controls during childhood and adolescence,
• suggesting that genetic and/or early environmental influences on brain
• development in ADHD are fixed, nonprogressive, and unrelated to
• stimulant treatment
• Castellanos et al. 2002
• Objective: To compare regional brain volumes at initial scan and their change over time in medicated and previously unmedicated patients with ADHD and healthy controls.
• Case-control study conducted from 1991-2001 of 152 children and adolescents with ADHD and 139 aged-matched controls
• Outcome measure: initial volumes and prospective age-related changes of total cerebrum, cerebellum, gray and white matter for the 4 major lobes of the brain were compared.
• Unmedicated children with ADHD also exhibited strikingly smaller total
• white matter volumes compared with controls and with medicated children with ADHD.Frontal and temporal gray matter, caudate, and cerebellar volumes
• correlated significantly with parent- and clinician-rated severity
• measures within the ADHD sample

Connectivity

• In like with the idea that connectivity is affected in the brain with the white matter, the idea is that there is a disruption in the default mode network
• Contributes to difficulty in processing information
• DMN: network of brain regions that have been noted to be active when an individual is not focused on the outside world and the brain is at wakeful rest.
• When we become alert the DMN switches off, brain regions alternate.
• Idea is that DMN is actually more persistent in ADHD and emerges into active alert state. Invading ability to focus because day-dreaming mode has not switched off.
• Sonuga-Barke & Castellanos 2007; Fair et al. 2010
• Identified distinct regions in the brain to show where these differences are.
• Tasks that have looked at these default mode networks involve putting someone in a scanner and telling them to not actively engage with anything.

Summary

• ADHD has been linked to:
• 1. Delay in grey matter development, especially in the prefrontal cortex
• 2. Decreased white matter and smaller caudate nucleus and cerebellum
• 3. Impaired connectivity of the default mode network
• 4. Dysregulation of the dopamine system
• Need a large number of participants: challening to work on that
• Understand better how the neurobiological deficits can be better linked to the cognitive deficits in ADHD. A number of the neurobiological underpinnings is pointing towards difficulty in frontal areas e.g. inhibition
• HOW does neurobiology link to cognitive markers

Link Biological and Cognitive Differences

• Try and make links between biological and cognitive levels.
• Make 3 core links
• Too little dopamine in prefrontal cortex as evident in neurological evidence that could affect executive dysfunction difficulties.
• Too much dopamine in Striatum: Problems in processing reward and affects reaction time difficulties.

1. Too little dopamine in PFC

• Too little dopamine in the prefrontal cortex leads to executive dysfunction problems
• Executive functions are needed
• for reasoning, problem solving etc
• They depend on a neural circuit
• in which prefrontal cortex play a central role and are impaired by damage to,
• or dysfunction in, PFC.
• The three core EFs from which
• more complex ones are built are 1. Inhibitory control (resisting strong
• inclination to do one thing and instead do what is most needed or appropriate;
• exercising self-control 2. Working memory (holding information in mind and
• working with it: mentally manipulating ideas, relating what you are learning,
• and 3. Cognitive flexibility (being able to change perspective or the focus of
• attention, thinking outside the box to come up with other ways to solve a
• problem
• There is evidence that when
• ADHD involves hyperactivity, the primary disorder is in the striatum and
• involves a striatal-frontal loop
• As dopamine transporter play an
• important role in the dopamine clearance in the striatum, it follows that
• polymorphism of the dopamine transporter 1 gene should have an important
• consequence for these subtypes of ADHD. (Barr et al. 2001)
• The primary cause of the
• cognitive deficits in ADHD such as inattention, and poor working memory lies in
• the PFC, not the striatum
• This is consistent with the different
• actions of methylphenidate at low doses.
• At low doses, methylphenidate
• preferentially increases dopamine neurotransmission in the PFC
• Methylpheniate in low doses,
• not only inhibits domapine reuptake (as it does at high dose) but also
• prefentially stimulates release of dopamine and norepinephrine.