Frontostriatal deficits in unipolar major depression
ABSTRACT Recent accounts of major depression have tended to focus on dysfunction of frontothalamic-striatal reentrant circuits as a possible source of the disorder. Evidence of frontostriatal involvement in unipolar major depression from lesion and neuropsychological studies, and functional and structural imaging studies is examined. The high incidence of depressive symptomatology following left frontal and basal ganglia lesions implicate these as possible sites of dysfunction. Neuropsychological evidence indicates similar deficits in patients with major depression, perhaps with dorsolateral prefrontal deficits most prominent. Structural imaging studies report frontal and basal ganglia (BG) abnormalities particularly in cases of late-age onset depression. Resting state functional imaging studies show deficits in dorsolateral, anterior cingulate (medial frontal), and BG structures. Activation imaging studies show less consistent evidence of dorsolateral deficit, while anterior cingulate deficit is more consistently demonstrated. Variability in findings across studies may reflect differences between subtypes of depression and differences in methodology. Possible involvement of the BG in the psychomotor retardation of depression is examined. It is concluded that, while there is evidence of frontostriatal deficit in major depression, the exact nature of such deficits is uncertain. Issues such as component vs. system dysfunction need to be addressed.
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ABSTRACT: To illuminate candidate neural working mech-anisms of Mindfulness-Based Cognitive Therapy (MBCT) in the treatment of recurrent depressive disorder, parallel to the potential interplays between modulations in electro-cortical dynamics and depressive symptom severity and self-compassionate experience. Linear and nonlinear α and γ EEG oscillatory dynamics were examined concomitant to an affective Go/NoGo paradigm, pre-to-post MBCT or natural wait-list, in 51 recurrent depressive patients. Spe-cific EEG variables investigated were; (1) induced event-related (de-) synchronisation (ERD/ERS), (2) evoked power, and (3) inter-/intra-hemispheric coherence. Sec-ondary clinical measures included depressive severity and experiences of self-compassion. MBCT significantly downregulated α and γ power, reflecting increased cortical excitability. Enhanced α-desynchronisation/ERD was observed for negative material opposed to attenuated α-ERD towards positively valenced stimuli, suggesting acti-vation of neural networks usually hypoactive in depression, related to positive emotion regulation. MBCT-related increase in left-intra-hemispheric α-coherence of the fron-to-parietal circuit aligned with these synchronisation dynamics. Ameliorated depressive severity and increased self-compassionate experience pre-to-post MBCT corre-lated with α-ERD change. The multi-dimensional neural mechanisms of MBCT pertain to task-specific linear and non-linear neural synchronisation and connectivity network dynamics. We propose MBCT-related modulations in dif-fering cortical oscillatory bands have discrete excitatory (enacting positive emotionality) and inhibitory (disengag-ing from negative material) effects, where mediation in the α and γ bands relates to the former. Keywords Major Depressive Disorder (MDD) · Mindfulness-Based Cognitive Therapy (MBCT) · ERD/ERS · Oscillatory EEG · α-Band coherence · γ-Band · EEG power IntroductionCognitive Neurodynamics 02/2015; 9(1):13-29. DOI:10.1007/s11571-014-9308-y · 1.77 Impact Factor
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ABSTRACT: Neuropsychiatric symptoms (NPS) are very common in neurodegenerative diseases and are a major contributor to disability and caregiver burden. There is accumulating evidence that NPS may be a prodrome and/or a “risk factor” of neurodegenerative diseases. The medications used to treat these symptoms in younger patients are not very effective in patients with neurodegenerative disease and may have serious side effects. An understanding of the neurobiology of NPS is critical for the development of more effective intervention strategies. Targeting these symptoms may also have implications for prevention of cognitive or motor decline. Molecular brain imaging represents a bridge between basic and clinical observations and provides many opportunities for translation from animal models and human post-mortem studies to in vivo human studies. Molecular brain imaging studies in Alzheimer's disease (AD) and Parkinson's disease (PD) are reviewed with a primary focus on positron emission tomography studies of NPS. Future directions for the field of molecular imaging in AD and PD to understand the neurobiology of NPS will be discussed.Neuroscience & Biobehavioral Reviews 11/2014; 49. DOI:10.1016/j.neubiorev.2014.11.010 · 10.28 Impact Factor
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ABSTRACT: Background Functional magnetic resonance imaging (fMRI) research suggests that both adult and adolescent major depressive disorder (MDD) is marked by aberrant connectivity of the default mode network (DMN) during resting-state. However, emotional dysresgulation is also a key feature of MDD. No studies to date have examined emotion-related DMN pathology in adolescent depression. Comprehensively understanding the dynamics of DMN connectivity across brain states in depressed individuals with short disease histories could provide insight into the etiology of MDD. Methods We collected fMRI data during an emotion identification task and also during resting-state from 26 medication-free adolescents (13-17 years) with MDD and 37 well-matched healthy controls (HCL). We examined between-group differences in blood oxygenation level-dependent task responses, emotion-dependent, and resting-state functional connectivity of the two primary nodes of the DMN: medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC). Additionally, we examined between-group differences in DMN functional connectivity and its relationship to depression severity and onset. Results Relative to HCL, unmedicated MDD adolescents demonstrated reduced mPFC and PCC emotion-related deactivation and greater mPFC and PCC emotion-dependent functional connectivity with precuneus, cingulate gyrus, and striatum/subcallosal cingulate gyrus. Importantly, PCC-subcallosal cingulate connectivity remained inflexibly elevated in MDD versus HCL during resting-state. Lastly, stronger PCC emotion-dependent functional connectivity was associated with greater depression severity and an earlier age of depression onset. Conclusions Adolescent depression is associated with inflexibly elevated DMN connections. Given recent evidence of DMN maturation throughout adolescence, our findings suggest that early-onset depression adversely impacts normal development of functional brain networks.Biological psychiatry 09/2014; DOI:10.1016/j.biopsych.2014.09.002 · 9.47 Impact Factor