Bipolar disorder and neurophysiologic mechanisms

Abstract

Recent studies have suggested that some variants of bipolar disorder (BD) may be due to hyperconnectivity between orbitofrontal (OFC) and temporal pole (TP) structures in the dominant hemisphere. Some initial MRI studies noticed that there were corpus callosum abnormalities within specific regional areas and it was hypothesized that developmentally this could result in functional or effective connectivity changes within the orbitofrontal-basal ganglia-thalamocortical circuits. Recent diffusion tensor imaging (DTI) white matter fiber tractography studies may well be superior to region of interest (ROI) DTI in understanding BD. A "ventral semantic stream" has been discovered connecting the TP and OFC through the uncinate and inferior longitudinal fasciculi and the elusive TP is known to be involved in theory of mind and complex narrative understanding tasks. The OFC is involved in abstract valuation in goal and sub-goal structures and the TP may be critical in binding semantic memory with person-emotion linkages associated with narrative. BD patients have relative attenuation of performance on visuoconstructional praxis consistent with an atypical localization of cognitive functions. Multiple lines of evidence suggest that some BD alleles are being selected for which could explain the enhanced creativity in higher-ability probands. Associations between ROI's that are not normally connected could explain the higher incidence of artistic aptitude, writing ability, and scientific achievements among some mood disorder subjects.

Keywords: artistic aptitude; bipolar disorder; creativity; diffusion tensor imaging; inferior fronto-occipital fasciculus; inferior longitudinal fasciculus; mood dysphoria; uncinate fasciculus; ventral semantic stream; white matter tractography; writing ability.

Figure 1

In the top picture is the diffusion tensor imaging tractography output for a healthy control. In the bottom picture is a representative tractography output from a bipolar disorder patient. All patients were on lithium monotherapy or combined therapy consisting of lithium, atypical neuroleptics and selective serotonin reuptake inhibitors. The bipolar disorder sample consisted of 8 males and 8 females with a mean age of 41 years. Note the much greater density and thickness of the red colored fibers in the bipolar disorder subjects in the bottom picture. The red tortuous pathway consists of reconstructed fibers connecting the left subgenual cingulate which is depicted in green and the left amygdalo-hippocampal complex depicted in purple. The blue lines represent reconstructed fibers connecting the left amygdalo-hippocampal complex to the rest of the brain. Copyright © 2007, Nature Publishing Group. Reproduced with permission from Houenou J, Wessa M, Douaud G, et al. 2007. Increased white matter connectivity in euthymic bipolar patients: Diffusion tensor tractography between the subgenual cingulate and the amygdalo-hippocampal complex. Mol Psychiatry, 12:1001–10.

Figure 2

Left illustration depicts the direct pathway from the posterior cortices to the prefrontal cortex. The inferior occipitofrontal fasciculus connects the posterior temporal areas and the orbital and lateral prefrontal regions. Middle illustration consists of the first segment of the indirect pathway. The inferior longitudinal fasciculus links the posterior occipitotemporal regions with the temporal pole and this fiber tract courses underneath the inferior occipitofrontal fasciculus. Right illustration depicts the second component of the indirect pathway. The uncinate fasciculus connects the anterior and medial temporal lobe with the orbitofrontal regions. Copyright © 2005, Oxford University Press. Adapted with permission from Catani M, ffytche DH. 2005. The rises and falls of disconnection syndromes. Brain, 128:2224–39.

Figure 3

Copyright © 1996, Elsevier. Adapted with permission from Nakamura K, Kubota K. 1996. The primate temporal pole: Its putative role in object recognition and memory. Behav Brain Res, 77:53–77. Abbreviations: HIP, hippocampus; PFC, prefrontal cortex; TPv, the ventral temporopolar cortex; TPd, the dorsal temporopolar cortex; aER, anterior entorhinal cortex; pER, posterior entorhinal cortex; aTE, anterior area TE; pTE, posterior area TE; TE Brodmann’s areas 20 and 21; TH & TF are cortical areas at the posterior end of the temporal lobe and are often referred to a parahippocampal cortex; STG, superior temporal gyrus; STP, superior temporal polysensory area; 7, superior parietal lobule; 35 and 36 are known as the perirhinal cortex.

Figure 4

The lateral orbitofrontal basal ganglia-thalamocortical circuit. The ventromedial head of the caudate nucleus receives input from the superior temporal gyrus, the inferior temporal gyrus and the anterior cingulate area. The closed loop of the lateral orbitofrontal circuit is completed by the return from these two regions of the thalamus to the lateral orbitofrontal cortex. Copyright © 1986. Redrawn and adapted from Alexander GE, DeLong MR, Strick PL. 1986. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci, 9:357–81.

Figure 5

The medial orbitofrontal – basal ganglia loop. Copyright © 1996, American Psychiatric Publishing. Adapted with permission from Zald DH, Kim SW. 1996. Anatomy and function of the orbital frontal cortex. I: Anatomy, neurocircuitry, and obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci, 8:125–38. Abbreviations: ACA, anterior cingulate area (light blue); AMG, amygdale (purple); CD, caudate nucleus (dark blue); ENT, entorhinal cortex (brown); ITG, inferior temporal gyrus; OFC, orbitofrontal cortex (pink); STG, superior temporal gyrus; Thal, thalamus (green); VS, ventral striatum (orange).