Program & Abstract Book - EPFL Latsis Symposium 2009

EPFL Latsis Symposium 2009: Understanding Violence
S-2
Abstracts for Speakers
th e n e u r o b i o l o g y o f impulsivity a n D a g g r e ss
i o n in aDhD (co n t i n u e D )
Lesch, Klaus-Peter
Department of Psychiatry, Psychsomatics, and Psychotherapy,
University of Würzburg, Germany
as predisposing environmental risk factors. While prenatal and parental risk
factors may be critical mediators of influences on the risk, the association
between these variables and ADHD is generally indirect.
Converging evidence from animal and human studies including structural
and functional neuroimaging implicates dysregulation of prefrontal–striatal–
thalamic– cerebellar excitatory and inhibitory circuits with broadening to a
multi-pathway framework in the pathophysiology of ADHD. It is widely accepted
that ADHD is the common final behavioral consequence of an array
of dysfunctions in each of several independent systems, such as cognitive,
motivational, and executive pathways, as well as circuitries of stress adaptation
and emotion regulation. Executive functions, which consist of a set
of higher order thought processes required for adaptive and future-oriented
behavior (e.g. deliberate suppression of a response to achieve a later, internally
represented goal) and are controlled by frontal-subcortical circuits,
include behavioral inhibition, working memory, attention setshifting, interference
control, planning, and sustained attention. Impairment of executive
functions with failure of inhibitory control; dysregulation of brain systems
mediating reward and response cost; and deficits in arousal, activation,
and effortful control, are central to the pattern of neuropsychological deficits.
Deficits in arousal and effort lead to state-dependent cognitive deficits
and underscore the view of an impairment in regulating cognitive functions
rather than core deficits in any single function. Inattention but not hyperactivity/impulsivity
is associated with deficits in executive functioning and
poor academic achievement, whereas hyperactivity/impulsivity appears to
be more closely related to dysfunctions of reward mechanisms.
Functional neuroimaging studies have assessed the degree of brain activation
associated with neuropsychological tasks of attention and disinhibition.
The findings are consistent with the structural studies indicating delays in
brain maturation processes and locating abnormalities of brain activation
in patients with ADHD in fronto–subcortical–cerebellar circuits. Since the
spectrum of ADHD features is not explained by a single neuropsychological
deficit, disorder-associated impairments are heterogeneous and this complexity
corresponds with causal heterogeneity. Despite recognition of ADHD
as a neurodevelopmental condition, only few causal explanations have considered
the two-way interactions between pre-existing abnormal functioning
and biological, cognitive, emotional, motor and social developmental processes,
and their contribution to the expression of the clinical phenotype.
27