Biomedical Engineering Reference
In-Depth Information
Over the last ten years, neuroimaging has allowed the study of these neural
processes in humans and has started to dissect the contribution of individual
brain regions to the processing of motivationally significant information. Recent
structural and functional neuroimaging has implicated a number of these brain
regions in psychiatric disease.
Since Aquinas, Spinoza, and Bentham, a central question has been how
rewarding stimuli are experienced relative to aversive or painful events, and how
the experience of reward is translated across categories of stimuli that reinforce
behavior (9,22,240). Today, human neuroimaging studies (at the limits of their
current resolution) have provided evidence for a generalized circuitry processing
rewarding and aversive stimuli. Motivationally salient features of infused drugs
of abuse, fruit juice consumption, perceived beautiful faces or music, monetary
gains and losses, somatosensory pain, and cues of aversive events activate a
common set of distributed neural circuits that process rewards and sanctions
(3,19,24,27,35,37,38,88,137,189,200). Within some of these neural groups,
separate local circuits have been shown during electrophysiological studies of
mammals to selectively activate in response to distinct categories of rewarding
input (51,52). A number of human neuroimaging studies have started dissecting
the subcomponent processes of the functions processing reward/aversion infor-
mation (33,38). The results of human studies together with those in phylogeneti-
cally lower species (132,147,215) point to the existence of an informational
backbone (iBM) focused on processing reward/aversion information.
Circuits within this iBM have been reported to be functionally or structur-
ally altered in a number of neuropsychiatric illnesses (36,63,103,126,161,181,
223,225,257). This body of research suggests that these illnesses can be charac-
terized by distinct circuit-based alterations. If a subset of these circuit-based
alterations were shown to be heritable, they might serve as endophenotypes for
future genetic linkage studies. To be endophenotypes, or heritable/familial quan-
titative traits, these circuit-based alterations would need to correlate with indi-
viduals' risk of developing a disease but not be a sign of disease progression
(4,106). Along with state-sensitive alterations, circuitry-based quantitative traits
may serve as better diagnostic markers (121,186,241) than those currently used
for psychiatric diagnosis based on statistical associations of behavioral signs and
symptoms. A detailed characterization of neural circuits in affected individuals,
their family members, and family-based matched controls (thereby producing a
"systems biology map") may enable us to characterize the genetic and epigenetic
factors that combine to produce these circuit-based alterations. Supporting these
possibilities, recent studies involving presentation of motivationally salient
stimuli allude to a potential correspondence between events at the molecular and
brain circuitry levels (11,19,242). Correspondence of measures across scales of
brain function suggests that similar principles of organization may be operative
with extended molecular networks and with distributed neural groups (21; see
Part II, chapters 4 (by Wuchty, Ravasz, and Barabási) and 5 (by Krakauer), and
Part III, chapter 5.1 (by Reeke), this volume).
