Elsevier

Biological Psychiatry

Volume 57, Issue 10, 15 May 2005, Pages 1079-1088
Biological Psychiatry

Original article
Activity and Connectivity of Brain Mood Regulating Circuit in Depression: A Functional Magnetic Resonance Study

https://doi.org/10.1016/j.biopsych.2005.02.021Get rights and content

Background

Functional imaging studies indicate that imbalances in cortico-limbic activity and connectivity may underlie the pathophysiology of MDD. In this study, using functional Magnetic Resonance Imaging (fMRI), we investigated differences in cortico-limbic activity and connectivity between depressed patients and healthy controls.

Methods

Fifteen unmedicated unipolar depressed patients and 15 matched healthy subjects underwent fMRI during which they first completed a conventional block-design activation experiment in which they were exposed to negative and neutral pictures. Next, low frequency blood oxygenation dependent (BOLD) related fluctuations (LFBF) data were acquired at rest and during steady-state exposure to neutral, positive and negative pictures. LFBF correlations were calculated between anterior cingulate cortex (ACC) and limbic regions – amygdala (AMYG), pallidostriatum (PST) and medial thalamus (MTHAL) and used as a measure of cortico-limbic connectivity.

Results

Depressed patients had increased activation of cortical and limbic regions. At rest and during exposure to neutral, positive, and negative pictures cortico-limbic LFBF correlations were decreased in depressed patients compared to healthy subjects.

Conclusions

The finding of increased activation of limbic regions and decreased LFBF correlations between ACC and limbic regions is consistent with the hypothesis that decreased cortical regulation of limbic activation in response to negative stimuli may be present in depression.

Section snippets

Subjects

Medication free unipolar depressed outpatients were recruited from the outpatient clinic at University Hospital, Indiana University School of Medicine and by advertisement. Healthy subjects matched for age, sex and ethnicity were also recruited via advertisement. All subjects took part after signing an informed consent form approved by the Investigational Review Board (IRB) at Indiana University School of Medicine. Both patients and subjects were paid $50 for screening and $50 for MRI scan.

Results

Seventeen depressed patients and 17 healthy subjects completed the fMRI scan. Results are presented for 15 depressed and 15 age, sex and ethnicity matched healthy subjects. One patient was excluded because she reported that she was unable to attend to the pictures during the scan. One healthy subject was excluded due to failure of the proper acquisition of fMRI data leading to a warped image. One patient and 1 healthy subject were excluded because there were no close matches in terms of age,

Discussion

Activation data from this study confirmed results from previous reports that depression is associated with increased activation of limbic regions such as the AMYG, PST, MTHAL, and insula. In this study, cortical components of the MRC such as the AMPFC, DLPFC and ACC also showed increased activation in response to negative versus neutral stimuli. Other fMRI studies have also reported increased activation of these areas to be related to evoked sadness in healthy subjects (Teasdale et al 1999) and

References (60)

  • H.S. Mayberg et al.

    Regional metabolic effects of fluoxetine in major depressionserial changes and relationship to clinical response

    Biological Psychiatry

    (2000)
  • K.L. Phan et al.

    Functional neuroanatomy of emotiona meta-analysis of emotion activation studies in PET and fMRI

    Neuroimage.

    (2002)
  • M.L. Phillips et al.

    Neurobiology of emotion perception IThe neural basis of normal emotion perception

    Biological Psychiatry

    (2003)
  • D.A. Seminowicz et al.

    Limbic-frontal circuitry in major depressiona path modeling meta-analysis

    Neuroimage

    (2004)
  • Y.I. Sheline et al.

    Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatmentan fMRI study

    Biological Psychiatry

    (2001)
  • L.M. Shin et al.

    An fMRI study of anterior cingulate function in posttraumatic stress disorder

    Biological Psychiatry

    (2001)
  • G.J. Siegle et al.

    Can’t shake that feelingevent-related fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals

    Biological Psychiatry

    (2002)
  • P. Skudlarski et al.

    Emotions changes the functional connectivity measured by the fMRI time-course correlations

    Neuroimge

    (2000)
  • R. Adolphs

    The human amygdala and emotion

    The Neuroscientist

    (1999)
  • G.E. Alexander et al.

    Basal ganglia-thalamocortical circuitsparallel substrates for motor, oculomotor, “prefrontal” and “limbic” functions

    Progress in Brain Research

    (1990)
  • A. Anand et al.

    Abnormality of catecholamines and pathophysiology of bipolar disorder

  • Anand A, Li Y, Wang Y, Wu J, Gao S, Bukhari L, et al (in press): Antidepressant effect on connectivity of mood...
  • B.B. Biswal et al.

    Functional connectivity in the motor cortex of resting human brain

    Magnetic Resonance in Medicine

    (1995)
  • J.D. Bremner

    Sturctural changes in the brain in depression and relationship to symptom recurrence

    CNS Spectrums

    (2002)
  • J.W. Burruss

    Functional neuroanatomy of the frontal lobe circuits

    Radiology

    (2000)
  • N.K. Chen et al.

    Optimized distortion correction technique for echo planar imaging

    Magnetic Resonance in Medicine

    (2001)
  • H.D. Critchley

    The human cortex responds to an interoceptive challenge

    Proc Natl Acad Sci U S A

    (2004)
  • A.R. Damasio

    Towards a neuropathology of emotion and mood

    Nature

    (1997)
  • R.J. Davidson et al.

    The neural substrates of affective processing in depressed patients treated with venlafaxine

    American Journal of Psychiatry.

    (2003)
  • W.C. Drevets

    Functional neuroimaging studies of depressionthe anatomy of melancholia

    Annual Review of Medicine

    (1998)
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