Functional neuroanatomy of bipolar disorder: structure, function, and connectivity in an amygdala-anterior paralimbic neural system. Blond, B. N, Fredericks, C. A, & Blumberg, H. P Bipolar Disord., 14(4):340--355, June, 2012.
Functional neuroanatomy of bipolar disorder: structure, function, and connectivity in an amygdala-anterior paralimbic neural system [link]Paper  doi  abstract   bibtex   
bjectives In past decades, neuroimaging research in bipolar disorder has demonstrated a convergence of findings in an amygdala–anterior paralimbic cortex neural system. This paper reviews behavioral neurology literature that first suggested a central role for this neural system in the disorder and the neuroimaging evidence that supports it. Methods Relevant articles are reviewed to provide an amygdala–anterior paralimbic cortex neural system model of bipolar disorder, including articles from the fields of behavioral neurology and neuroanatomy, and neuroimaging. Results The literature is highly supportive of key roles for the amygdala, anterior paralimbic cortices, and connections among these structures in the emotional dysregulation of bipolar disorder. The functions subserved by their more widely distributed connection sites suggest that broader system dysfunction could account for the range of functions—from neurovegetative to cognitive—disrupted in the disorder. Abnormalities in some components of this neural system are apparent by adolescence, while others, such as those in rostral prefrontal regions, appear to progress over adolescence and young adulthood, suggesting a neurodevelopmental model of the disorder. However, some findings conflict, which may reflect the small sample sizes of some studies, and clinical heterogeneity and methodological differences across studies. Conclusions Consistent with models derived from early behavioral neurology studies, neuroimaging studies support a central role for an amygdala–anterior paralimbic neural system in bipolar disorder, and implicate abnormalities in the development of this system in the disorder. This system will be an important focus of future studies on the developmental pathophysiology, detection, treatment, and prevention of the disorder. Keywords: amygdala, bipolar disorder, prefrontal cortex Go to: Overview Neuroimaging research over the past several decades has yielded a convergent view of bipolar disorder (BD) that supports a central role for an amygdala–anterior paralimbic cortex neural system in the disorder. This model draws from early behavioral neurology reports of lesions in anterior paralimbic cortices and seizure foci in mesial temporal structures, such as the amygdala, in patients whose symptoms were similar to those of individuals with primary mood disorders. It also draws from neuroanatomic and neurobehavioral studies, which identified connections among the amygdala and anterior paralimbic structures, including the ventral prefrontal cortex (VPFC), insular cortex (IC), and temporopolar cortex (TPC), and the central role of this system of interconnected structures in emotional regulation. These studies also identified more widely distributed connection sites of this system including more rostral, dorsal and lateral prefrontal cortices (PFC), hippocampus, striatum, thalamus, cerebellum and hypothalamus (1–5). Together, the structures of this system subserve the phylogenetically broad range of functions characteristically disrupted in BD, from basic biological rhythm and neurovegetative processes, such as sleep and appetitive functions, to motivated behaviors and thought processes. These considerations suggest that impaired amygdala–anterior paralimbic functioning could contribute not only to the emotional dysregulation of BD, but also to the broader range of symptoms characteristic of acute mood episodes through disruption of the larger neural system. Structural and functional neuroimaging studies focusing on regional abnormalities have provided converging evidence supporting involvement of this system in BD, with the strongest evidence for abnormalities within the amygdala and VPFC. Abnormalities within each of the connection sites above have also been reported; although the hypothalamus has been relatively elusive given limitations of current neuroimaging technologies. In the past few years, implementation of new research techniques has provided data on connections between structures within this neural system in BD. Studies employing imaging methods such as diffusion tensor imaging (DTI), and functional connectivity analysis of functional magnetic resonance imaging (fMRI) data, have provided evidence to suggest important roles for both structural and functional connectivity abnormalities in the disorder. This article will review behavioral neurological and neuroanatomical studies that informed the neural system model of BD, the structural and functional neuroimaging studies that support abnormalities within the implicated regions, and more recent neuroimaging studies that support abnormalities within the connections among these regions. Studies that have contributed to a view of BD as a developmental disorder of this neural system will be reviewed, including evidence that abnormalities in subcortical limbic and paralimbic cortices appear to be established by adolescence, whereas differences in more rostral PFC areas may progress during adolescence and young adulthood. This article will also touch upon findings from genetic, postmortem histopathological, and neuropsychological studies that may inform understanding of the mechanisms that underlie the neural system findings.
@article{blond_functional_2012,
	title = {Functional neuroanatomy of bipolar disorder: structure, function, and connectivity in an amygdala-anterior paralimbic neural system},
	volume = {14},
	issn = {1398-5647},
	url = {http://dx.doi.org/10.1111/j.1399-5618.2012.01015.x},
	doi = {10.1111/j.1399-5618.2012.01015.x},
	abstract = {bjectives In past decades, neuroimaging research in bipolar disorder has
demonstrated a convergence of findings in an amygdala–anterior paralimbic
cortex neural system. This paper reviews behavioral neurology literature
that first suggested a central role for this neural system in the disorder
and the neuroimaging evidence that supports it. Methods Relevant articles
are reviewed to provide an amygdala–anterior paralimbic cortex neural
system model of bipolar disorder, including articles from the fields of
behavioral neurology and neuroanatomy, and neuroimaging. Results The
literature is highly supportive of key roles for the amygdala, anterior
paralimbic cortices, and connections among these structures in the
emotional dysregulation of bipolar disorder. The functions subserved by
their more widely distributed connection sites suggest that broader system
dysfunction could account for the range of functions—from neurovegetative
to cognitive—disrupted in the disorder. Abnormalities in some components
of this neural system are apparent by adolescence, while others, such as
those in rostral prefrontal regions, appear to progress over adolescence
and young adulthood, suggesting a neurodevelopmental model of the
disorder. However, some findings conflict, which may reflect the small
sample sizes of some studies, and clinical heterogeneity and
methodological differences across studies. Conclusions Consistent with
models derived from early behavioral neurology studies, neuroimaging
studies support a central role for an amygdala–anterior paralimbic neural
system in bipolar disorder, and implicate abnormalities in the development
of this system in the disorder. This system will be an important focus of
future studies on the developmental pathophysiology, detection, treatment,
and prevention of the disorder. Keywords: amygdala, bipolar disorder,
prefrontal cortex Go to: Overview Neuroimaging research over the past
several decades has yielded a convergent view of bipolar disorder (BD)
that supports a central role for an amygdala–anterior paralimbic cortex
neural system in the disorder. This model draws from early behavioral
neurology reports of lesions in anterior paralimbic cortices and seizure
foci in mesial temporal structures, such as the amygdala, in patients
whose symptoms were similar to those of individuals with primary mood
disorders. It also draws from neuroanatomic and neurobehavioral studies,
which identified connections among the amygdala and anterior paralimbic
structures, including the ventral prefrontal cortex (VPFC), insular cortex
(IC), and temporopolar cortex (TPC), and the central role of this system
of interconnected structures in emotional regulation. These studies also
identified more widely distributed connection sites of this system
including more rostral, dorsal and lateral prefrontal cortices (PFC),
hippocampus, striatum, thalamus, cerebellum and hypothalamus (1–5).
Together, the structures of this system subserve the phylogenetically
broad range of functions characteristically disrupted in BD, from basic
biological rhythm and neurovegetative processes, such as sleep and
appetitive functions, to motivated behaviors and thought processes. These
considerations suggest that impaired amygdala–anterior paralimbic
functioning could contribute not only to the emotional dysregulation of
BD, but also to the broader range of symptoms characteristic of acute mood
episodes through disruption of the larger neural system. Structural and
functional neuroimaging studies focusing on regional abnormalities have
provided converging evidence supporting involvement of this system in BD,
with the strongest evidence for abnormalities within the amygdala and
VPFC. Abnormalities within each of the connection sites above have also
been reported; although the hypothalamus has been relatively elusive given
limitations of current neuroimaging technologies. In the past few years,
implementation of new research techniques has provided data on connections
between structures within this neural system in BD. Studies employing
imaging methods such as diffusion tensor imaging (DTI), and functional
connectivity analysis of functional magnetic resonance imaging (fMRI)
data, have provided evidence to suggest important roles for both
structural and functional connectivity abnormalities in the disorder. This
article will review behavioral neurological and neuroanatomical studies
that informed the neural system model of BD, the structural and functional
neuroimaging studies that support abnormalities within the implicated
regions, and more recent neuroimaging studies that support abnormalities
within the connections among these regions. Studies that have contributed
to a view of BD as a developmental disorder of this neural system will be
reviewed, including evidence that abnormalities in subcortical limbic and
paralimbic cortices appear to be established by adolescence, whereas
differences in more rostral PFC areas may progress during adolescence and
young adulthood. This article will also touch upon findings from genetic,
postmortem histopathological, and neuropsychological studies that may
inform understanding of the mechanisms that underlie the neural system
findings.},
	number = {4},
	journal = {Bipolar Disord.},
	author = {Blond, Benjamin N and Fredericks, Carolyn A and Blumberg, Hilary P},
	month = jun,
	year = {2012},
	keywords = {Sep 20 import, duplicate},
	pages = {340--355}
}
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