The functional neuroanatomy of depression: Distinct roles for ventromedial and dorsolateral prefrontal cortex
Open accessAbstract
A primary aim in the neuroscientific study of depression is to identify the brain areas involved in the pathogenesis of symptoms. In this review, we describe evidence from studies employing various experimental approaches in humans (functional imaging, lesion method, and brain stimulation) that converge to implicate the ventromedial and dorsolateral sectors of prefrontal cortex as critical neural substrates for depression, albeit with distinct functional contributions. The putative roles of ventromedial and dorsolateral prefrontal cortex in depression are discussed in light of the results.
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rTMS for MDD most commonly targets the left hemisphere DLPFC, a key node in the functional pathophysiology thought to underlie depressive symptoms.
“Consistent with the original FDA label, rTMS for MDD most commonly targets the left hemisphere DLPFC, a key node in the functional pathophysiology thought to underlie depressive symptoms (21).”
From Adaptive trial for the treatment of depressive symptoms associated with concussion using accelerated intermittent theta burst stimulation (ADEPT): rationale, design and methods (2025) · cites this paper as [21]
The Brain stimulation studies section says dozens of studies investigated left dlPFC stimulation for depression, and the Summary and conclusion identifies dlPFC as a key neural substrate underlying depression. The paper does not establish that left dlPFC is the most common rTMS target or discuss the original FDA label. (LLM, conf=0.83)
Experimental — accuracy not yet measuredDamage to the ventromedial prefrontal cortex has been associated with emotional deficits including diminished guilt.
“Furthermore, damage to the ventromedial prefrontal cortex has been associated with emotional deficits including diminished guilt (Koenigs & Grafman, 2009)”
From A novel resting-state functional magnetic resonance imaging signature of resilience to recurrent depression (2017) · cites this paper as Koenigs & Grafman, 2009
Substantial evidence indicates that mPFC dysfunction plays a critical role in pathology of MDD.
“Substantial evidence indicates that mPFC dysfunction plays a critical role in the pathology of major depressive disorder (MDD) 203.”
From Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications (2022) · cites this paper as [203]
A review concluded that depression typically involves lower dorsolateral PFC activity, including dorsal ACC, and higher ventromedial PFC activity, including subgenual ACC.
“One recent review of brain function in depression [71] concluded that depression is typified by hypoactivation in dorsolateral PFC (including dorsal ACC), as well as hyperactivation in ventromedial PFC (including subgenual ACC).”
From Arrested development? Reconsidering dual-systems models of brain function in adolescence and disorders (2012) · cites this paper as [71]
Research efforts aimed at understanding the neural circuits underlying depression have been mainly devoted to the prefrontal cortex, hippocampus, and mesolimbic structures.
“Research efforts aimed at understanding the neural circuits underlying depression have been mainly devoted to the prefrontal cortex, hippocampus, and mesolimbic structures [12, 55, 56].”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [12]
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Erasing Fear Memories with Extinction Training: Figure 1.
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“Studies of major depression in humans observe abnormal neuronal morphology (Hercher et al., 2009), deficient activity (Koenigs and Grafman, 2009), and altered functional connectivity of mPFC (Frodl et al., 2010) correlated with the pathophysiology of depression and enhanced memory for negative…”
BackgroundNejati, V., Majdi, R., Salehinejad, M., & Nitsche, M. (2021) · Scientific Reports · doi:10.1038/s41598-021-81454-7 · Cited by 203 · see citing works
Mitchell, D. G. V. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.10.030 · Cited by 219 · see citing works
“It has been proposed that regions of vmPFCmay confer depressive symptoms either by playing a role in the generation of negative emotion, or by supporting self-awareness and therefore depressive rumination [151].”
Amelioration of Cognitive Control in Depression by Transcranial Direct Current Stimulation
Wolkenstein, L., & Plewnia, C. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.10.010 · Cited by 213 · see citing works
Optogenetic dissection of medial prefrontal cortex circuitry
Riga, D., Matos, M. R., Glas, A., Smit, A. B., Spijker, S., & Van den Oever, M. C. (2014) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2014.00230 · Cited by 208 · see citing works
“Taken together, over the years both clinical and preclinical research implicated the mPFC as a crucial mediator of depressive symptomatology (Koenigs and Grafman, 2009), which triggered a quest for causality and a clarification of the exact contributions of mPFC subregions and their distinct afferent and efferent proj…”
BackgroundTham, M. W., Woon, P. S., Sum, M. Y., Lee, T.-S. W., & Sim, K. (2010) · Journal of Affective Disorders · doi:10.1016/j.jad.2010.09.013 · Cited by 206 · see citing works
“White matter changes in post-mortem studies (see Table 1) The majority of the available studies investigated the prefrontal cortex (PFC) and in older individuals with depression (Cotter et al., 2002; Koenigs and Grafman, 2009; Regenold et al., 2007; Thomas et al., 2002a, 2003b).”
BackgroundtDCS for the treatment of depression: a comprehensive review
Palm, U., Hasan, A., Strube, W., & Padberg, F. (2016) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-016-0674-9 · Cited by 182 · see citing works
“The rationale for the use of tDCS in major depressive disorders has been based on the positive results of studies using TMS in depressed patients and the evidence that depressed patients show functional and also structural changes in several cortical regions, especially the left dorsolateral and ventromedial cortex, t…”
Microglia of Prefrontal White Matter in Suicide
Schnieder, T. P., Trencevska, I., Rosoklija, G., Stankov, A., Mann, J. J., Smiley, J., & Dwork, A. J. (2014) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000107 · Cited by 202 · see citing works
“Because the behavioral functions of dorsal and ventral prefrontal cortex differ (41, 64) and because the ventral cortex is more specifically implicated in suicidality (43, 65Y67), we analyzed the 2 regions separately.”
Korgaonkar, M. S., Grieve, S. M., Koslow, S. H., Gabrieli, J. D. E., Gordon, E., & Williams, L. M. (2011) · Human Brain Mapping · doi:10.1002/hbm.21178 · Cited by 205 · see citing works
“…tract connecting the frontal cortex with the temporal, occipital, and parietal lobes, with a particular bias toward fibers originating or terminating in the DLPFC. Frontal lobe dysfunction and its association with depression symptomology has been well established [Koenigs and Grafman, 2009].”
BackgroundZhao, Y.-J., Du, M.-Y., Huang, X.-Q., Lui, S., Chen, Z.-Q., Liu, J., Luo, Y., Wang, X.-L., Kemp, G. J., & Gong, Q.-Y. (2014) · Psychological Medicine · doi:10.1017/s0033291714000518 · Cited by 203 · see citing works
“…has shown grey matter changes in the left DLPFC, which is associated with top-down neuronal modulation of emotion (Smith et al. 2013); a defect in the regulation of negative affect due to DLPFC dysfunction is a plausible mechanism for DLPFC involvement in depression (Koenigs & Grafman, 2009).”
BackgroundApolipoproteins in the brain: implications for neurological and psychiatric disorders
Elliott, D. A., Weickert, C. S., & Garner, B. (2010) · Clinical Lipidology · doi:10.2217/clp.10.37 · Cited by 196 · see citing works
“The dorsolateral prefrontal cortex is a region that plays a critical role in attention and working memory and is implicated in psychiatric disorders, such as schizophrenia, autism and depression [169,170].”
BackgroundNoninvasive brain stimulation in psychiatric disorders: a primer
Brunoni, A. R., Sampaio-Júnior, B., Moffa, A. H., Aparicio, L. V. M., Gordon, P. C., Klein, I., Rios, R. M., Razza, L. B., Loo, C. K. A., Padberg, F., et al. (2018) · Brazilian Journal of Psychiatry · doi:10.1590/1516-4446-2017-0018 · Cited by 195 · see citing works
Why estrogens matter for behavior and brain health
Galea, L. A. M., Frick, K. M., Hampson, E., Sohrabji, F., & Choleris, E. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.03.024 · Cited by 180 · see citing works
HIV, Depression, and Cognitive Impairment in the Era of Effective Antiretroviral Therapy
Rubin, L. H., & Maki, P. M. (2019) · Current HIV/AIDS Reports · doi:10.1007/s11904-019-00421-0 · Cited by 181 · see citing works
Reproductive Steroid Regulation of Mood and Behavior
Schiller, C. E., Johnson, S., Abate, A., Schmidt, P. J., & Rubinow, D. R. (2016) · Comprehensive physiology · doi:10.1002/cphy.c150014 · Cited by 217 · see citing works
Noninvasive brain stimulation treatments for addiction and major depression
Dunlop, K., Hanlon, C. A., & Downar, J. (2017) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12985 · Cited by 171 · see citing works
Impact of early adversity on glucocorticoid regulation and later mental disorders
Strüber, N., Strüber, D., & Roth, G. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.10.015 · Cited by 173 · see citing works
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“modulates the effortful control of negative emotion [39], whereas”
BackgroundBerardis, D. D., Fornaro, M., Valchera, A., Cavuto, M., Perna, G., Nicola, M. D., Serafini, G., Carano, A., Pompili, M., Vellante, F., et al. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19102888 · Cited by 175 · see citing works
“Functional studies have associated the deficits in cognitive flexibility showed by depressed patients to specific alterations in the structure and connection of the prefrontal cortex (PFC) [44,45].”
BackgroundTata, D. A., & Anderson, B. J. (2010) · Physiology & Behavior · doi:10.1016/j.physbeh.2009.09.008 · Cited by 173 · see citing works
“Like the hippocampus, the frontal lobe dysfunction has been implicated in depression [29-31] and the frontal lobe, like the hippocampus undergoes structural modification in response to glucocorticoids and stress [32-35].”
BackgroundCarlson, E. J., Saarikallio, S. H., Toiviainen, P., Bogert, B., Kliuchko, M., & Brattico, E. (2015) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2015.00466 · Cited by 175 · see citing works
“To test the relation between emotion regulation in the brain and music regulation strategies, we focused our analysis on the PFC, in which emotional processes are controlled and regulated (Ochsner and Gross, 2005; Koenigs and Grafman, 2009).”
BackgroundMethodResultInfluentialHulvershorn, L. A., Cullen, K. R., & Anand, A. (2011) · Brain Imaging and Behavior · doi:10.1007/s11682-011-9134-3 · Cited by 170 · see citing works
“…neuroimaging reviews in depressed adults largely converge on findings of decreased volume in widespread cortical regions (Fitzgerald et al. 2006; Koenigs and Grafman 2009), although there is evidence of acute enlargement of subcortical regions, such as the amygdala (Frodl et al. 2003; van…”
BackgroundCortico-limbic morphology separates tinnitus from tinnitus distress
Leaver, A. M., Seydell‐Greenwald, A., Turesky, T. K., Morgan, S., Kim, H. J., & Rauschecker, J. P. (2012) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2012.00021 · Cited by 164 · see citing works
“Previous work in mood disorders consistently identifies reduced GM in vmPFC and subcallosal anterior cingulate (scACC) in individuals suffering from clinical depression and anxiety (Drevets et al., 1997; Mayberg, 1997; Koenigs and Grafman, 2009).”
BackgroundMentalizing in female inpatients with major depressive disorder
Fischer-Kern, M., Fonagy, P., Kapusta, N. D., Luyten, P., Boss, S., Naderer, A., Blüml, V., & Leithner, K. (2013) · Journal of Nervous & Mental Disease · doi:10.1097/nmd.0b013e3182845c0a · Cited by 157 · see citing works
“Contemporary models of neuronal circuitry in depression suggest that depression may be associated with an imbalance in activity between the ventromedial cortex and the dorsolateral prefrontal cortex, with the former subserving more affective functions and the latter subserving more cognitive or executive functions (Ko…”
BackgroundLiu, J. H., Fang, J., Wang, Z., Rong, P., Yang, H., Fan, Y., Wang, X., Park, J., Yu, J. Z., Liu, C., et al. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.08.003 · Cited by 160 · see citing works
“Furthermore, fMRI studies have found hemispheric asymmetry during emotional processing in depressed and non-depressed individuals (Herrington et al., 2010; Jackson et al., 2003; Koenigs & Grafman, 2009).”
BackgroundDeep brain stimulation targets for treating depression
Drobisz, D., & Damborská, A. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.11.004 · Cited by 159 · see citing works
“Additionally, decreased activity was observed throughout the study in the ventromedial prefrontal cortex, which has been reported to be hyperactive in depression [61].”
Fotopoulou, A., Pernigo, S., Maeda, R., Rudd, A., & Kopelman, M. (2010) · Brain : a journal of neurology · doi:10.1093/brain/awq233 · Cited by 126 · see citing works
“In previous studies, bilateral medial prefrontal cortex and related limbic and striatopallido-thalamic lesions have been associated with lower levels of depression than damage to dorsal prefrontal areas or more posterior lesions (for review see Koenigs and Grafman, 2009).”
BackgroundSalehinejad, M. A., Ghanavai, E., Rostami, R., & Nejati, V. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.12.036 · Cited by 154 · see citing works
Brunoni, A. R., Vanderhasselt, M., Boggio, P. S., Fregni, F., Dantas, E. M., Mill, J. G., Lotufo, P. A., & Benseñor, I. M. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.04.020 · Cited by 154 · see citing works
Functional Connectivity Signatures of Parkinson’s Disease
Tessitore, A., Cirillo, M., & Micco, R. D. (2019) · Journal of Parkinson s Disease · doi:10.3233/jpd-191592 · Cited by 150 · see citing works
Gyurak, A., Patenaude, B., Korgaonkar, M. S., Grieve, S. M., Williams, L. M., & Etkin, A. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.02.037 · Cited by 149 · see citing works
Li, L. M., Violante, I. R., Leech, R., Ross, E., Hampshire, A., Opitz, A., Rothwell, J. C., Carmichael, D. W., & Sharp, D. J. (2018) · Human Brain Mapping · doi:10.1002/hbm.24420 · Cited by 148 · see citing works
Anosmia Leads to a Loss of Gray Matter in Cortical Brain Areas
Bitter, T., Gudziol, H., Burmeister, H. P., Mentzel, H., Guntinas‐Lichius, O., & Christian Gaser, B. (2010) · Chemical Senses · doi:10.1093/chemse/bjq028 · Cited by 146 · see citing works
“In patients with major depression, a volume reduction of the ACC, dlPFC, and the SCG (Yucel et al. 2008; Koenigs and Grafman 2009) and in patients with PD similar atrophy areas in the ACC and NAc (Summerfield et al.”
BackgroundFarb, N. A. S., Anderson, A. K., Bloch, R. T., & Segal, Z. V. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.03.009 · Cited by 141 · see citing works
Long-Term Behavioral Effects of Post-weaning Social Isolation in Males and Females
Walker, D. M., Cunningham, A. M., Gregory, J. K., & Nestler, E. J. (2019) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2019.00066 · Cited by 139 · see citing works
Korgaonkar, M. S., Grieve, S. M., Etkin, A., Koslow, S. H., & Williams, L. M. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.252 · Cited by 135 · see citing works
“The dLPFC dysfunction has been previously shown linked to impaired cognitive processing in MDD (Fitzgerald et al, 2006; Koenigs and Grafman, 2009).”
BackgroundInfluentialChanging Brain Networks Through Non-invasive Neuromodulation
To, W. T., De Ridder, D., Hart Jr., J., & Vanneste, S. (2018) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2018.00128 · Cited by 135 · see citing works
“The left DLPFC has been found to be hypoactive in patients with depression and an increase in activity is associated with antidepressant response (Fitzgerald et al., 2006b; Koenigs and Grafman, 2009).”
BackgroundVoineskos, D., Blumberger, D. M., Zomorrodi, R., Rogasch, N. C., Farzan, F., Foussias, G., Rajji, T. K., & Daskalakis, Z. J. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.09.032 · Cited by 135 · see citing works
Ellis, M. J., Leddy, J. J., & Willer, B. S. (2016) · Frontiers in Neurology · doi:10.3389/fneur.2016.00136 · Cited by 134 · see citing works
Caldieraro, M. A., & Cassano, P. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.09.048 · Cited by 134 · see citing works
Brunoni, A. R., Ferrucci, R., Fregni, F., Boggio, P. S., & Priori, A. (2012) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2012.05.016 · Cited by 133 · see citing works
“…could be a better strategy as some studies suggest that subjects with depression may exhibit prefrontal cortex asymmetry (hyperactivation on the right and hypoactivation on the left prefrontal cortex (Koenigs and Grafman, 2009)) and therefore, this protocol can act simultaneously in both areas.”
Portella, M. J., de Diego-Adeliño, J., Gómez-Ansón, B., Morgan-Ferrando, R., Vives, Y., Puigdemont, D., Pérez-Egea, R., Ruscalleda, J., Álvarez, E., & Pérez, V. (2011) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2010.08.010 · Cited by 127 · see citing works
Lei, Y., Wang, J., Wang, D., Li, C., Liu, B., Fang, X., You, J., Guo, M., & Lu, X.-Y. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0352-1 · Cited by 131 · see citing works
Hill, A. T., Rogasch, N. C., Fitzgerald, P. B., & Hoy, K. E. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.03.006 · Cited by 128 · see citing works
The cholinergic system and depression
Dagytė, G., den Boer, J. A., & Trentani, A. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.02.023 · Cited by 126 · see citing works
“Different subregions of the prefrontal cortex are suggested o contribute to diverse symptoms of depression, and their role as been previously reviewed [134].”
BackgroundPirnia, T., Joshi, S. H., Leaver, A. M., Vasavada, M., Njau, S., Woods, R. P., Espinoza, R., & Narr, K. L. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.102 · Cited by 122 · see citing works
Lehéricy, S., Vaillancourt, D. E., Seppi, K., Monchi, O., Rektorová, I., Antonini, A., McKeown, M. J., Masellis, M., Berg, D., Rowe, J. B., et al. (2017) · Movement Disorders · doi:10.1002/mds.26968 · Cited by 122 · see citing works
“This cortical area has a pivotal role in the prefrontal-limbic network and is also involved in cognition and executive functions.(98,99) Using rs-fMRI, the role of abnormal connectivity of the amygdala in dysfunctional mood modulation has been emphasized in depressed PD patients.”
BackgroundNeurocognitive Functioning in Depressed Young People: A Systematic Review and Meta-Analysis
Goodall, J., Fisher, C. A., Hetrick, S. E., Phillips, L., Parrish, E. M., & Allott, K. (2018) · Neuropsychology Review · doi:10.1007/s11065-018-9373-9 · Cited by 122 · see citing works
The role of monoamine oxidase enzymes in the pathophysiology of neurological disorders
Jones, D. N., & Raghanti, M. A. (2021) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2021.101957 · Cited by 116 · see citing works
Major depression, cognitive dysfunction and Alzheimer's disease: Is there a link?
Sierksma, A. S. R., van den Hove, D. L. A., Steinbusch, H. W. M., & Prickaerts, J. (2010) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2009.10.021 · Cited by 139 · see citing works
“In contrast, the dorsolateral PFC is associated more with cognitive or executive functions, since it is highly connected to the orbitofrontal cortex and the hippocampus (Koenigs and Grafman, 2009; Wall and Messier, 2001).”
BackgroundAlexander, L., Wood, C. M., Gaskin, P. L. R., Sawiak, S. J., Fryer, T. D., Hong, Y. T., McIver, L., Clarke, H. F., & Roberts, A. C. (2020) · Nature Communications · doi:10.1038/s41467-020-19167-0 · Cited by 100 · see citing works
Crider, A., Feng, T., Pandya, C. D., Davis, T., Nair, A., Ahmed, A. O., Baban, B., Turecki, G., & Pillai, A. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.03.004 · Cited by 112 · see citing works
“We found a significant increase in the short isoform of VCAM-1 (~50 KDa) in the PFC of WT mice following CUS [Fig 5A; two-way ANOVA, stress, F(1,10) = 45.”
Lowe, C. J., Manocchio, F., Safati, A. B., & Hall, P. A. (2018) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2018.02.004 · Cited by 115 · see citing works
To do it now or later: The cognitive mechanisms and neural substrates underlying procrastination.
Zhang, S.-M., Liu, P., & Feng, T.-Y. (2019) · Wiley Interdisciplinary Reviews: Cognitive Science · doi:10.1002/wcs.1492 · Cited by 97 · see citing works
The Role of the Microbiome-Brain-Gut Axis in the Pathogenesis of Depressive Disorder
Młynarska, E., Gadzinowska, J., Tokarek, J., Forycka, J., Szuman, A., Franczyk, B., & Rysz, J. (2022) · Nutrients · doi:10.3390/nu14091921 · Cited by 109 · see citing works
“The dysfunction of the prefrontal cortex in humans embraced hyperactivity in ventral-medial and hypoactivity in dorsolateral areas [57].”
BackgroundDamage to the left ventromedial prefrontal cortex impacts affective theory of mind
Leopold, A., Krüeger, F., Monte, O. D., Pardini, M., Pulaski, S. J., Solomon, J. M., & Grafman, J. H. (2011) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsr071 · Cited by 109 · see citing works
Self-citationOpen questions in current models of antidepressant action
Tanti, A., & Belzung, C. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00585.x · Cited by 109 · see citing works
“…depression is associated with decreased baseline activity in the temporal cortex and in the insula, increased activity in the cerebellum (Fitzgerald et al., 2008), in the ventromedial PFC (see Koenigs and Grafman, 2009, for a review) and in the anterior cingulate cortex (Drevets, 2000).”
BackgroundMust, A., Horváth, S., Németh, V. L., & Janka, Z. (2013) · Frontiers in Psychology · doi:10.3389/fpsyg.2013.00732 · Cited by 109 · see citing works
“Parallel to a decline in vmPFC activation patients tend to be influenced more by aversive stimuli (Koenigs and Grafman, 2009).”
BackgroundOh, D. H., Son, H., Hwang, S., & Kim, S. H. (2012) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2011.09.001 · Cited by 103 · see citing works
Lan, M. J., Chhetry, B. T., Liston, C., Mann, J. J., & Dubin, M. (2016) · Brain Stimulation · doi:10.1016/j.brs.2016.02.011 · Cited by 96 · see citing works
Philippi, C. L., Motzkin, J. C., Pujara, M. S., & Koenigs, M. (2015) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2015.10.005 · Cited by 93 · see citing works
“Our results associating depression severity with increased functional connectivity between posterior sgACC and dlPFC are directly relevant to literature identifying the sgACC and the dlPFC as key regions altered in depression (Drevets et al., 2008b; Koenigs et al., 2008; Koenigs and Grafman, 2009; Mayberg, 2003).”
BackgroundResultSelf-citationPrins, J., Olivier, B., & Korte, S. M. (2011) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2011.594039 · Cited by 98 · see citing works
“The PFC is involved in overall cognitive functioning that allows an organism to get things done; problem solving and time planning, reinforcement, reappraisal and suppression of negative affect [25-27].”
BackgroundSensorimotor modulation of mood and depression: An integrative review
Canbeyli, R. S. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.11.002 · Cited by 98 · see citing works
Rajkowska, G., Mahajan, G., Maciąg, D., Sathyanesan, M., Iyo, A. H., Moulana, M., Kyle, P. B., Woolverton, W. L., Miguel-Hidalgo, J. J., Stockmeier, C. A., et al. (2015) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2015.04.010 · Cited by 99 · see citing works
“…with the role of the vPFC in emotional, motivational and social behaviors, and thereby contribute to the constellation of symptoms comprising MDD (Drevets et al., 2008; Koenigs & Grafman, 2009; Kringelbach, 2005; Kringelbach and Rolls, 2004; Price and Drevets, 2010; Rolls and Grabenhorst, 2008).”
BackgroundAlonzo, A., Fong, J. S., Ball, N., Martin, D. M., Chand, N., & Loo, C. K. A. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.04.041 · Cited by 97 · see citing works
A data-driven single-cell and spatial transcriptomic map of the human prefrontal cortex
Huuki-Myers, L. A., Spangler, A., Eagles, N. J., Montgomery, K. D., Kwon, S. H., Guo, B., Grant‐Peters, M., Divecha, H. R., Tippani, M., Sriworarat, C., et al. (2024) · Science · doi:10.1126/science.adh1938 · Cited by 97 · see citing works
Jett, J. D., Bulin, S. E., Hatherall, L. C., McCartney, C. M., & Morilak, D. A. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.01.017 · Cited by 92 · see citing works
“In depressed patients, cognitive dysfunction is associated with hypoactivity and compromised glutamate transmission in the PFC (Anand et al., 2005; Bermpohl et al., 2009; Koenigs and Grafman, 2009; Disner et al., 2011).”
BackgroundSmith, R., Chen, K., Baxter, L., Fort, C., & Lane, R. D. (2013) · Journal of Affective Disorders · doi:10.1016/j.jad.2012.07.029 · Cited by 95 · see citing works
- Authors
- Koenigs, M., & Grafman, J.
- Affiliations
- University of Wisconsin–Madison (US)
- National Institutes of Health (US)
- Corresponding author
- Koenigs, Michael
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 201
- Issue
- 2
- Pages
- 239-243
- ISSN
- 0166-4328 (ISSN-L)
- PMC
- PMC2680780
- OpenAlex
- W2156809536
- Cited by
- 956
- References
- 39
- Citations by year
- 2026: 43 · 2025: 54 · 2024: 60 · 2023: 60 · 2022: 83 · 2021: 88 · 2020: 64 · 2019: 80 · 2018: 77 · 2017: 52 · 2016: 70 · 2015: 55 · 2014: 38 · 2013: 41 · 2012: 38
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (Z01NS002792)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- depression, ventromedial prefrontal cortex, dorsolateral prefrontal cortex, prefrontal cortex, functional neuroanatomy, brain lesions, transcranial magnetic stimulation, functional imaging
- MeSH terms
- Brain Mapping, Depression, Depressive Disorder, Humans, Prefrontal Cortex, Transcranial Magnetic Stimulation
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