Functional neuroanatomy of bipolar disorder: structure, function, and connectivity in an amygdala–anterior paralimbic neural system

Abstract

Objectives-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. OverviewNeuroimaging 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, s...

Modulation of brain response to emotional conflict as a function of current mood in bipolar disorder: Preliminary findings from a follow-up state-based fMRI study

“…A better understanding of the cerebral mechanisms and impact of mood switching in BD is crucial in order to develop or improve treatments for this disorder. Functional neuroimaging studies in patients with BD have evidenced changes in limbic and prefrontal networks relative to healthy people (for reviews, see Blond et al, 2012;, suggesting anomalies in neural circuits involved in affective regulation that are potentially responsible for emotional homeostasis or its loss . However, few studies have sought to determine a neural signature of BD in different mood states.…”

Neuroimagem no transtorno bipolar

“…Essa variação nos resultados obtidos em adultos pode ser justificada pelos efeitos neurotrófi-cos de fármacos utilizados na estabilização do humor, pelas variações genéticas de cada indivíduo ou pelos aspectos relacionados ao neurodesenvolvimento. De fato, alguns estudos que utilizaram PET ou SPECT demonstraram anormalidades funcionais da amígdala -hipermetabolismo na fase depressiva em alguns estudos, versus hipometabolismo em outros, nas fases tanto de depressão quanto de mania 26 . Por outro lado, vários estudos que utilizaram RNMf e mediram resposta a estímulos emocionais positivos utilizando tarefas cognitivas sem valência emocional descreveram hiperatividade da amígdala apenas na fase de mania 27 .…”

“…Por outro lado, vários estudos que utilizaram RNMf e mediram resposta a estímulos emocionais positivos utilizando tarefas cognitivas sem valência emocional descreveram hiperatividade da amígdala apenas na fase de mania 27 . Os estudos de RNM que mediram o hipocampo encontraram resultados muito variáveis, o que pode ser explicado em parte por variações genéticas (carreamento do alelo Met, associado a menores volumes hipocampais), efeitos de tratamento (uso de lítio, associado a aumento do volume hipocampal) ou hormô-nios sexuais 26 . Entretanto, uma menor concentração de NAA no hipocampo de pacientes adultos eutímicos foi documentada em uma metanálise 20 .…”

A Systems Neuroscience Approach to the Pathophysiology of Pediatric Mood and Anxiety Disorders

“…Emotional dys-regulation is a hallmark feature of pediatric BD. One of the bestreplicated finding in pediatric BD is an impaired ability in processing emotions (including emotion labeling deficits), assessed through face processing paradigms (for reviews, see Blond et al 2012;Chen et al 2011;Delvecchio et al 2012;Houenou et al 2011;Kupferschmidt and Zakzanis 2011;Strakowski et al 2012). In addition to impaired emotional processing, studies have also revealed cognitive control deficits in pediatric BD (for a review, see Passarotti and Pavuluri 2011).…”

“…Together, these difficulties in emotional processing may contribute to the social impairment commonly observed in BD, since the ability to read social cues and facial expressions is essential for adaptive social functioning. fMRI findings: Research examining the neural circuitry mediating face emotion processing in BD implicates dysfunction in the fronto-limbic-striatal network (for reviews, see Blond et al 2012;Chen et al 2011;Delvecchio et al 2012;Houenou et al 2011;Kohler et al 2011;Kupferschmidt and Zakzanis 2011;Pavuluri and Passarotti 2008;Strakowski et al 2012). Abnormalities in amygdala function during face emotion processing are observed consistently in both children (for a review, see Pavuluri and Passarotti 2008) and adults with BD (for a review, see Strakowski et al 2012).…”