Marcel Kinsbourne

Etiologic Subtypes of Attention-Deficit/Hyperactivity Disorder: Brain Imaging, Molecular Genetic and Environmental Factors and the Dopamine Hypothesis

Multiple theories of Attention-Deficit/Hyper- activity Disorder (ADHD) have been proposed, but one that has stood the test of time is the dopamine deficit theory. We review the narrow literature from recent brain imaging and molecular genetic studies that has improved our understanding of the role of dopamine in manifestation of symptoms of ADHD, performance deficits on neuropsychological tasks, and response to stimulant medication that constitutes the most common treatment of this disorder. First, we consider evidence of the presence of dopamine deficits based on the recent literature that (1) confirms abnormalities in dopamine-modulated frontal-striatal circuits, reflected by size (smaller-than-average components) and function (hypoactivation); (2) clarifies the agonist effects of stimulant medication on dopaminergic mechanisms at the synaptic and circuit level of analysis; and (3) challenges the most-widely accepted ADHD-related neural abnormality in the dopamine system (higher-than-normal dopamine transporter [DAT] density). Second, we discuss possible genetic etiologies of dopamine deficits based on recent molecular genetic literature, including (1) multiple replications that confirm the association of ADHD with candidate genes related to the dopamine receptor D4 (DRD4) and the DAT; (2) replication of differences in performance of neuropsychological tasks as a function of the DRD4 genotype; and (3) multiple genome-wide linkage scans that demonstrate the limitations of this method when applied to complex disorders but implicate additional genes that may contribute to the genetic basis of ADHD. Third, we review possible environmental etiologies of dopamine deficits based on recent studies of (1) toxic substances that may affect the dopamine system in early development and contribute substantially to the etiology of ADHD; (2) fetal adaptations in dopamine systems in response to stress that may alter early development with lasting effects, as proposed by the developmental origins of health and disease hypothesis; and (3) gene-environment interactions that may moderate selective damage or adaptation of dopamine neurons. Based on these reviews, we identify critical issues about etiologic subtypes of ADHD that may involve dopamine, discuss methods that could be used to address these issues, and review old and new theories that may direct research in this area in the future.

Sensory and attention abnormalities in autistic spectrum disorders

Individuals with autistic spectrum disorders (ASDs) often experience, describe and exhibit unusual patterns of sensation and attention. These anomalies have been hypothesized to result from overarousal and consequent overfocused attention. Parents of individuals with ASD rated items in three domains, ‘sensory overreactivity’, ‘sensory underreactivity’ and ‘sensory seeking behaviors’, of an expanded version of the Sensory Profile, a 103-item rating scale developed for the present study. Parents also rated symptom severity, overselective attention and exceptional memory, and completed the Vineland Adaptive Behavior Scales. Of 222 rated subjects, 144 had complete data. Cluster analysis showed the predicted overfocused pattern of sensation and attention, comprising overreactivity, perseverative behavior and interests, overfocused attention and exceptional memory in 43 percent of this sample. This pattern was striking in 10 percent. The neurological basis of overreactivity and overfocusing is discussed in relation to the overarousal hypothesis. Attention is drawn to its considerable prevalence in the ASD population.

Can children with autism recover? If so, how?

Although Autism Spectrum Disorders (ASD) are generally assumed to be lifelong, we review evidence that between 3% and 25% of children reportedly lose their ASD diagnosis and enter the normal range of cognitive, adaptive and social skills. Predictors of recovery include relatively high intelligence, receptive language, verbal and motor imitation, and motor development, but not overall symptom severity. Earlier age of diagnosis and treatment, and a diagnosis of Pervasive Developmental Disorder-Not Otherwise Specified are also favorable signs. The presence of seizures, mental retardation and genetic syndromes are unfavorable signs, whereas head growth does not predict outcome. Controlled studies that report the most recovery came about after the use of behavioral techniques. Residual vulnerabilities affect higher-order communication and attention. Tics, depression and phobias are frequent residual co-morbidities after recovery. Possible mechanisms of recovery include: normalizing input by forcing attention outward or enriching the environment; promoting the reinforcement value of social stimuli; preventing interfering behaviors; mass practice of weak skills; reducing stress and stabilizing arousal. Improving nutrition and sleep quality is non-specifically beneficial.

Time estimation by patients with frontal lesions and by Korsakoff amnesics

We studied time estimation in patients with frontal damage (F) and alcoholic Korsakoff (K) patients in order to differentiate between the contributions of working memory and episodic memory to temporal cognition. In Experiment 1, F and K patients estimated time intervals between 10 and 120 s less accurately than matched normal and alcoholic control subjects. F patients were less accurate than K patients at short (< 1 min) time intervals whereas K patients increasingly underestimated durations as intervals grew longer. F patients overestimated short intervals in inverse proportion to their performance on the Wisconsin Card Sorting Test. As intervals grew longer, overestimation yielded to underestimation for F patients. Experiment 2 involved time estimation while counting at a subjective 1/s rate. F patients subjective tempo, though relatively rapid, did not fully explain their overestimation of short intervals. In Experiment 3, participants produced predetermined time intervals by depressing a mouse key. K patients underproduced longer intervals. F patients produced comparably to normal participants, but were extremely variable. Findings suggest that both working memory and episodic memory play an individual role in temporal cognition. Turnover within a short-term working memory buffer provides a metric for temporal decisions. The depleted working memory that typically attends frontal dysfunction may result in quicker turnover, and this may inflate subjective duration. On the other hand, temporal estimation beyond 30 s requires episodic remembering, and this puts K patients at a disadvantage.

Attention and the right-ear advantage: What is the connection?

Dichotic listening originally was a means of studying attention. Half a century ago Doreen Kimura parlayed the dichotic method into a noninvasive indicator of lateralized cerebral language representation. The ubiquitous right-ear advantage (REA) for verbal material was accepted as a concomitant of left-sided language lateralization and preferential conduction of right-ear messages to the left hemisphere. As evidence has accumulated over the past 50years showing the REA to be dynamic and modifiable, the concept of attention has become essential for interpreting the findings. Progress in understanding the role of attention has been manifested as a transition from efforts to document attention effects to efforts to characterize their mechanisms. We summarize the relevant evidence, trace the evolution of explanatory models, and outline contemporary accounts of the role of attention in dichotic listening.

Allocation of Attention in Dichotic Listening: Differential Effects on the Detection and Localization of Signals

In 2 dichotic listening experiments, 96 normal right-handed adults attended selectively to the left and right ear and divided their attention equally between both ears. Participants listened for specified targets and reported the ear of entry. The material consisted of pairs of consonant-vowel syllables in Experiment 1 and pairs of rhyming consonant-vowel-consonant words in Experiment 2. Both experiments yielded a right-ear advantage for detection and for localization. Attention instructions had no effect on detection. However, focusing attention on 1 ear increased the number of targets attributed to that ear while decreasing the number of targets attributed to the opposite ear. The dissociation between detection and localization indicates that volitional shifts of attention influence late (response selection) processes rather than early (stimulus identification) processes. Selective-listening effects can be accounted for by a 2-stage model in which a fixed input asymmetry is modulated by a biased selection of responses.

Divergent thinking styles of the hemispheres: how syllogisms are solved during transitory hemisphere suppression.

Psychiatric patients solved syllogisms while recovering from transitory ictal suppression of one hemisphere by electroconvulsive therapy (ECT). The premises were familiar or unfamiliar, true or false. While the right hemisphere was suppressed, syllogisms were usually solved by theoretical, deductive reasoning even when the factual answer was known a priori, the premises were obviously false and the conclusions were absurd. While their left hemisphere was suppressed, the same subjects applied their prior knowledge; if the syllogism content was unfamiliar or false, they refused to answer. We postulate a left-hemisphere mechanism capable of decontextualized mental operations and a right-hemisphere mechanism, the operation of which is context-bound and incapable of abstraction. We show that each hemisphere tends to overextend its perspective on the problem and that in the intact brain they both contribute to an extent that depends on the characteristics of the problem at hand.

Acquired Epileptiform Aphasia: A Dimensional View of Landau-Kleffner Syndrome and the Relation to Regressive Autistic Spectrum Disorders

Acquired epileptiform aphasia (AEA) is characterized by deterioration in language in childhood associated with seizures or epileptiform electroencephalographic abnormalities. Despite an extensive literature, discrepancies and contradictions surround its definition and nosological boundaries. This paper reviews current conceptions of AEA and highlights variations in the aphasic disturbance, age of onset, epileptiform EEG abnormalities, temporal course, and long-term outcome. We suggest that AEA, rather than being a discrete entity, is comprised of multiple variants that have in common the features of language regression and epileptiform changes on EEG. Viewed this way, we argue that AEA can be conceptualized on a spectrum with other epileptiform neurocognitive disorders that may share pathophysiological features. The implications of this viewpoint are discussed, with emphasis on parallels between the AEA variants and regressive autistic spectrum disorders.

Left hemisphere specialization for response to positive emotional expressions : A divided output methodology

An extensive literature credits the right hemisphere with dominance for processing emotion. Conflicting literature finds left hemisphere dominance for positive emotions. This conflict may be resolved by attending to processing stage. A divided output (bimanual) reaction time paradigm in which response hand was varied for emotion (angry; happy) in Experiments 1 and 2 and for gender (male; female) in Experiment 3 focused on response to emotion rather than perception. In Experiments 1 and 2, reaction time was shorter when right-hand responses indicated a happy face and left-hand responses an angry face, as compared to reversed assignment. This dissociation did not obtain with incidental emotion (Experiment 3). Results support the view that response preparation to positive emotional stimuli is left lateralized.

Embodied anticipation: A neurodevelopmental interpretation.

This article proposes an approach to the brains role in communication that treats the brain as the vehicle of a multi-scale embodiment of anticipation. Instead of conceptualizing anticipation as something a brain is able to do when circumstances seem to require it, this study proposes that anticipation is continuous and ongoing because to anticipate is an inherent design characteristic of the brain. Correspondingly, there is no anticipation module in the brain, and no focal lesion selectively abolishes the brains propensity to anticipate. Anticipation is a wager based on previous experience. It readies a response to an event that has yet to occur. First, the anticipation is “embrained” in terms of covert neural representations, and then it is embodied in terms of rudiments of the embrained actions and expressions of feeling. This study applies this concept to conversation and shows that nested anticipations precede the dynamics of the actual encounter and continue at each turn as long as the conversation lasts.