Dianne Melinda Sheppard

The Neurodevelopmental Frontostriatal Disorders: Evolutionary Adaptiveness and Anomalous Lateralization☆

The frontostriatal system (dorsolateral prefrontal cortex, lateral orbitofrontal cortex, anterior cingulate, supplementary motor area, and associated basal-ganglia structures) is subject to a range of neurodevelopmental disorders: Tourettes syndrome (TS), obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), autism, and probably depression. The system is responsible for our adaptive responses (initiation, execution, or withholding) to environmental situations, and the above disorders, involving effectively excessive release or withholding of various types of response, are all a consequence of changes in specific frontostriatal regions. The disorders all have a genetic component, and their persistence in the genome indicates that their clinical manifestations may also be associated, perhaps in low levels in close relatives, with certain adaptive advantages in given situations. Thus autism is associated with computational careers, depression with literary creativity, SCZ with lateral thinking and the Odyssean personality, ADHD with an Ice-Age readiness to respond, OCD with a focused range of interests, and TS with competitive sports and jazz improvisation. The disorders are all highly comorbid, and which one predominantly manifests may depend on how the frontostriatal system happens to be compromised as a result of inherited genetic predispositions and environmental contingency. We review the adaptive nature of the various subclinical manifestations and the evidence for concomitant phenomena (possibly epiphenomena): alterations in structural, functional, and behavioral lateralization in each syndrome. Indeed it is not clear that altered lateralization in frontostriatal disorders of a neurodevelopmental origin generally has any adaptive significance; it may often simply serve as a marker for altered regulatory function of the frontostriatal system, alterations which in low genetic dosage or penetrance continue to play an adaptive role in clinically unaffected close relatives of probands, but which, in high dosage or penetrance in the probands themselves, are generally deleterious.

Autism and ADHD: How far have we come in the comorbidity debate?

The potential for the coexistence of the developmental disorders autism and attention-deficit/hyperactivity disorder (ADHD) in any one individual has for a long time been a contentious issue. While from a neurobiological perspective it is possible, and even highly likely, that ADHD and autism might clinically co-exist, our major diagnostic classification systems (DSM-IV-TR and ICD-10) currently preclude such a dual-diagnosis. The aim of the current review is to summarise current diagnostic criteria and treatment strategies for the two disorders, relevant theories of developmental dysfunction, and update the state of the debate regarding comorbidity. Evidence from clinical, neuroimaging and neuropsychological domains is considered, and similarities and differences between the two disorders are identified. Suggestions for future research into the comorbid profiles of these disorders are proposed, with a strong emphasis placed on the neuropsychological assessment of executive functioning as a potentially useful tool for both identifying similarities, and differentiating the disorders.

Tourette’s and comorbid syndromes: Obsessive compulsive and attention deficit hyperactivity disorder. a common etiology?

Tourettes syndrome (TS), a neuropsychiatric movement disorder that manifests itself in childhood, is often associated with comorbid symptomatology, such as obsessions, compulsions, hyperactivity, distractibility, and impulsivity. Epidemiological studies suggest that a substantial number of TS patients develop clinical levels of obsessive-compulsive disorder (OCD) and/or attention deficit hyperactivity disorder (ADHD). This review aims to provide an integrated account of the three disorders in terms of their comorbidity. Neuroimaging studies suggest that all three disorders involve neuropathology of the basal-ganglia thalamocortical (BGTC) pathways: TS in the sensorimotor and limbic BGTC circuits; OCD in the prefrontal and limbic BGTC pathways; and ADHD in the sensorimotor, orbitofrontal, and limbic BGTC circuits. The pattern of comorbidity and other evidence indicates that the TS gene(s) may be responsible for a spectrum of disorders, including OCD and ADHD, but also that the disorders OCD and ADHD can exist in their own right with their own etiologies.

Effects of stimulant medication on the lateralisation of line bisection judgements of children with attention deficit hyperactivity disorder

OBJECTIVES Deficits in the maintenance of attention may underlie problems in attention deficit hyperactivity disorder (ADHD). Children with ADHD also show asymmetric attention deficits in traditional lateralisation and visuospatial orienting tasks, suggesting right hemispheric (and left hemispace) attentional disturbance. This study aimed to examine the lateralisation of selective attention in ADHD; specifically, the effect of a moving, random dot background, and stimulant medication in the line bisection task. METHODS The performance of children with ADHD, on and off methylphenidate, was examined using a computerised horizontal line bisection task with moving and blank backgrounds. Twenty children with a DSM-IV diagnosis of ADHD participated with 20 controls, individually matched for age, sex, grade at school, and IQ. Twelve of the 20 children with ADHD were on stimulant medication at the time of testing. Horizontal lines of varying length were presented in the centre of a computer screen, with either a blank background, or a moving, random dot field. The random dots moved either leftward or rightward across the screen at either 40 mm/s or 80 mm/s. RESULTS The children with ADHD off medication bisected lines significantly further to the right compared with controls, who showed a small leftward error. Methylphenidate normalised the performance of the children with ADHD for the task with the moving dots. CONCLUSIONS These results support previous evidence for a right hemispheric hypoarousal theory of attentional dysfunction, and are consistent with the emerging picture of a lateralised dysfunction of frontostriatal circuitry in ADHD.

Age and responding-hand related changes in performance of neurologically normal subjects on the line-bisection and chimeric-faces tasks.

This study investigated age and responding-hand (left, right, and bimanual) related changes in visuospatial attention. Two tasks were completed by 107 neurologically normal right-handed subjects ranging in age from 5 to 70 years and distributed across four age groups. Task-specific differences between groups were apparent. In the line-bisection task, the younger and older groups displayed symmetrical neglect while the young and middle groups displayed pseudoneglect. In the chimeric-faces task the leftward bias was less pronounced in the older group and more susceptible to responding-hand effects in the middle and older groups. Whilst results, especially those of the bimanual method, provided strong support for an activation model, they imposed an age limitation on its appropriateness as an explanation for performance on the chimeric-faces task. Results are discussed as reflecting changes in the corpus callosum and right hemisphere.

Examining the development of attention and executive functions in children with a novel paradigm.

The development of attention and executive functions in normal children (7-12 years) was investigated using a novel selective reaching task, which involved reaching as rapidly as possible towards a target, while at times having to ignore a distractor. The information processing paradigm allowed the measurement of various distinct dimensions of behaviour within a single task. The largest improvements in vigilance, set-shifting, response inhibition, selective attention, and impulsive responding were observed to occur between the ages of 8 and 10, with a plateau in performance between 10 and 12 years of age. These findings, consistent with a step-wise model of development, coincide with the observed developmental spurt in frontal brain functions between 7 and 10 years of age, and indicate that attention and executive functions develop in parallel. This task appears to be a useful research tool in the assessment of attention and executive functions, within a single task. Thus it may have a role in determining which cognitive functions are most affected in different childhood disorders.

MOTOR PREPARATION, MOTOR EXECUTION, ATTENTION, AND EXECUTIVE FUNCTIONS IN ATTENTION DEFICIT/HYPERACTIVITY DISORDER (ADHD)

Attention and executive functions were investigated in medicated and unmedicated children with ADHD combined type using a novel selective reaching task. This task involved responding as rapidly as possible to a target while at times having to ignore a distractor. Results indicated that unmedicated children with ADHD showed slow and inaccurate responding. Slow responding reflected problems at the stage of movement preparation but not movement execution. An attentional impairment, rather than a motor planning problem per se, appeared to underlie the slow movement preparation. Inaccurate responding reflected problems with response inhibition and selective attention, impulsivity, set-shifting, and difficulties in maintaining vigilance. Although medicated children with ADHD did not show slow movement preparation, they did show some response inaccuracy, resulting especially from impulsive responding.These findings suggest that ADHD is characterized by slow motor preparation (but not motor execution), and deficits in selective attention, vigilance, and executive functions. Preliminary results suggest that stimulant medication may resolve some of these motor, attentional and executive function deficits. We gratefully acknowledge the assistance of Claire Graham and Judy Matulick at Frankston Child and Adolescent Mental Health Service (Southern Health) in the recruitment of research participants. Many thanks also to Maree Farrow in the Psychology Department at Monash University and two anonymous reviewers for their helpful comments on this manuscript.

Individualized Alpha Activity and Frontal Asymmetry in Major Depression

Lateralized differences in frontal alpha power in individuals with major depressive disorder (MDD) are thought to reflect an aberrant affective processing style. However research into anterior alpha asymmetry and MDD has often produced conflicting results. The current study aimed to investigate whether individualized alpha bandwidths provide a more sensitive measure of anterior alpha asymmetry in MDD than the traditional fixed 8–13 Hz alpha band. Resting EEG was recorded from 34 right-handed female participants (18 controls, 16 MDD). Each participants Individual Alpha Frequency was used to delineate a broad individualized alpha band and three individualized narrow alpha sub-bands: lower alpha1, lower alpha 2 and upper alpha. Activity within the broad and narrow individualized bandwidths and within the traditional fixed alpha band were used to compare a) controls and acutely depressed individuals and b) medicated and unmedicated MDD participants. Individualizing and subdividing the alpha bandwidth did not add appreciably to the sensitivity of anterior alpha asymmetry in MDD as no significant differences in lateralized alpha power between controls and MDD participants were observed in any alpha bandwidth. This finding was consistent under two reference schemes and across multiple scalp locations. Within the MDD group, antidepressant use was associated with significantly greater right than left hemispheric power in the lower alpha 1 band. The relevance of this finding is discussed in relation to the electrophysiological correlates of antidepressant medication use, lateralized differences in affective processing and treatment resistant MDD.

The interaction of shape- and location-based priming in object categorisation: Evidence for a hybrid “what + where” representation stage

The relationship between part shape and location is not well elucidated in current theories of object recognition. Here we investigated the role of shape and location of object parts on recognition, using a classification priming paradigm with novel 3D objects. In Experiment 1, the relative displacement of two parts comprising the prime gradually reduced the priming effect. In Experiment 2, presenting single-part primes in locations progressively different from those in the composite target had no effect on priming. In Experiment 3, manipulating the relative position of composite prime and target strongly affected priming. Finally, in Experiment 4 the relative displacement of single-part primes and composite targets did influence response time. Together, these findings are best interpreted in terms of a hybrid theory, according to which conjunctions of shape and location are explicitly represented at some stage of visual object processing.

Movement sequencing in children with Tourette's syndrome and attention deficit hyperactivity disorder.

Little research has been conducted to examine sequential motor functioning of children with Tourettes syndrome (TS) and attention deficit hyperactivity disorder (ADHD). Movement sequencing performance for a group of 12 children with TS and 24 children with ADHD children (12 taking and 12 not taking stimulant medication) and matched control subjects was examined using a serial choice reaction time button‐pressing procedure. Aspects of movement preparation and execution were measured for 10 sequential two‐way choice points along a response board that extinguished the illuminated target buttons at certain specific times contingent on the previous button press or release. The level of advance information was systematically reduced to provide three levels of reduction of advance information, including no reduction, moderate reduction, and high reduction. Children with TS and ADHD (unmedicated) showed larger increases in down time, reflecting aspects of movement preparation, for the highest level of reduction of advance information than did their respective control groups. These deficits are suggestive of underlying frontostriatal dysfunction. Furthermore, the normalization of performance for children with ADHD taking stimulant medication assists in the confirmation of the validity of such a clinical diagnosis and seems to add to the clinical efficacy of this form of treatment, which has previously been associated with improvements for predominantly attentional and inhibitory symptoms of ADHD.