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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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“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]
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“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
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“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]
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“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]
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“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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Citations
Cites
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BackgroundA technical guide to tDCS, and related non-invasive brain stimulation tools
Woods, A. J., Antal, A., Bikson, M., Boggio, P. S., Brunoni, A. R., Celnik, P. A., Cohen, L. G., Fregni, F., Herrmann, C. S., Kappenman, E. S., et al. (2015) · Clinical Neurophysiology · doi:10.1016/j.clinph.2015.11.012 · Cited by 1,548
“Thus, in most cases, electrodes are positioned over the area associated with the pathology under study – for instance, in depression electrodes are placed over the dorsolateral prefrontal cortex, an area in which activity is pathologically altered (Koenigs and Grafman, 2009).”
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“In view of anatomical connectivity and functional specialization, the prefrontal cortex is divided into two subregions: ventromedial prefrontal cortex (vmPFC) and dorsolateral sectors (dlPFC) [48].”
BackgroundDepression and sickness behavior are Janus-faced responses to shared inflammatory pathways
Maes, M., Berk, M., Goehler, L., Song, C., Anderson, G., Gałecki, P., & Leonard, B. (2012) · BMC Medicine · doi:10.1186/1741-7015-10-66 · Cited by 629
“regions that process viscerosensory and regulation of emotion in humans [145-147] and rodents [148].”
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Brunoni, A. R., Valiengo, L. D. C. L., Baccaro, A., Zanao, T. A., de Oliveira, J. F., Goulart, A. C., Boggio, P. S., Lotufo, P. A., Benseñor, I. M., & Fregni, F. (2013) · JAMA Psychiatry · doi:10.1001/2013.jamapsychiatry.32 · Cited by 617
“Finally, we performed anodal stimulation over the left DLPFC and cathodal stimulation over the right DLPFC (bifrontal montage), aiming not only to increase MDD left hypoactivity but also to modulate the potential left-right prefrontal imbalance observed in this disorder.(28)”
MethodWeigand, A., Horn, A., Caballero, R., Cooke, D. L., Stern, A. P., Taylor, S. F., Press, D. Z., Pascual‐Leone, Á., & Fox, M. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.10.028 · Cited by 492
Dysregulation of Limbic and Auditory Networks in Tinnitus
Leaver, A. M., Renier, L. A., Chevillet, M. A., Morgan, S., Kim, H. J., & Rauschecker, J. P. (2011) · Neuron · doi:10.1016/j.neuron.2010.12.002 · Cited by 470
“Both these conditions are associated with structural abnormalities in vmPFC (Drevets et al., 1997; Koenigs and Grafman, 2009; Tanabe et al., 2009) similar to the ones we report in individuals with chronic tinnitus.”
Cognitive Network Neuroscience
Medaglia, J. D., Lynall, M.-E., & Bassett, D. S. (2015) · Journal of Cognitive Neuroscience · doi:10.1162/jocn_a_00810 · Cited by 419
“The dorsolateral pFCs (Koenigs & Grafman, 2009) and inferior frontal gyrus (Shamay-Tsoory, Aharon-Peretz, & Perry 2008) have been implicated as nodes in a distributed emotion processing system with differentiable functional roles.”
BackgroundBarrett, J., & Fleming, A. S. (2011) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2010.02306.x · Cited by 433
“…Roceri et al., 2004; Roth, Lubin, Funk, & Sweatt, 2009; human studies: Clark, Chamberlain, & Sahakian, 2009; Hercher, Turecki, & Mechawar, 2009; Koenigs & Grafman, 2009; Rogers et al., 2004; Savitz & Drevets, 2009; Siegle, Thompson, Carter, Steinhauer, & Thase, 2007) and in some cases…”
Gut microbiome and depression: what we know and what we need to know
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A review of post-concussion syndrome and psychological factors associated with concussion
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“This is convergent with functional studies of depression demonstrating hyperactivity within the ventromedial prefrontal cortex and hypoactivity in the dorsolateral prefrontal cortex [14].”
ResultThe Role of Early Growth Response 1 (EGR1) in Brain Plasticity and Neuropsychiatric Disorders
Duclot, F., & Kabbaj, M. (2017) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2017.00035 · Cited by 376
“…of EGR1 in the PFC of depressed patients is particularly interesting and could represent one of the substrates for the anatomical and functional alterations observed in major depressive disorders in this brain area (Krishnan and Nestler, 2008; Koenigs and Grafman, 2009; Lefaucheur et al., 2017).”
BackgroundAbnormal Structural Networks Characterize Major Depressive Disorder: A Connectome Analysis
Korgaonkar, M. S., Fornito, A., Williams, L. M., & Grieve, S. M. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.02.018 · Cited by 367
“Meta-analyses of functional imaging studies in depression have highlighted the role of the DLPFC, the ACC, and the dmPFC regions in depression (2,34,35).”
Immediate Early Genes, Memory and Psychiatric Disorders: Focus on c-Fos, Egr1 and Arc
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“It should be noticed that this region has consistently been reported to be affected in depressed patients and in animal models of depression (Krishnan and Nestler, 2008; Koenigs and Grafman, 2009; Duclot and Kabbaj, 2017a,b; Lefaucheur et al., 2017).”
ResultDownar, J. H., Geraci, J., Salomons, T. V., Dunlop, K., Wheeler, S. M., McAndrews, M. P., Bakker, N., Blumberger, D. M., Daskalakis, Z. J., Kennedy, S. H., et al. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.10.026 · Cited by 362
“Dorsomedial prefrontal cortex lesions confer a strong risk of depressive symptoms (21,22).”
BackgroundHippocampal-Prefrontal Interactions in Cognition, Behavior and Psychiatric Disease
Sigurdsson, T., & Duvarci, S. (2016) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2015.00190 · Cited by 309
“The primate PFC is organized into several subregions but can be broadly separated into a dorsolateral division that is involved in cognitive functions such as executive control, attention and working memory, and a ventromedial (or orbitomedial) division more involved in emotional and motivational regulation (Koenigs a…”
BackgroundInfluentialCircuit-Based Corticostriatal Homologies Between Rat and Primate
Heilbronner, S. R., Rodríguez-Romaguera, J., Quirk, G. J., Groenewegen, H. J., & Haber, S. N. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.05.012 · Cited by 321
“For example, activation of a25 and a32 is related to negative affect in major depressive disorder (52,53) and drug-related cues in addiction (54,55).”
Yan, Z., & Rein, B. (2022) · Molecular Psychiatry · doi:10.1038/s41380-021-01092-3 · Cited by 300
“In human MDD patients, ketamine administration similarly increases glutamate/glutamine cycling in PFC [225].”
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“Although this suggests the absence of an ongoing global cerebral metabolic deficit, extensive literature supports the role of a regional neurotransmitter as well as cerebral metabolic and blood flow imbalances in the pathophysiology of mood disorders [62–64].”
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Emotion regulation predicts symptoms of depression over five years
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“…findings from affective neuroscience indicate that MDD is associatedwith abnormal activation patterns in brain areas thought to be involved in effective emotion regulation (e.g., Farb, Anderson, Bloch, & Segal, 2011; Koenigs & Grafman, 2009; Ritchey, Dolcos, Eddington, Strauman, & Cabeza, 2011).”
BackgroundFibromyalgia: A Critical and Comprehensive Review
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“dorsolateral prefrontal cortex (DLPFC) is strongly implicated in protecting from depression [210] and activation of the”
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“…alterations in expression of synaptophysin (a synaptic vesicle membrane protein) and GSK-3 β (part of the Wnt signaling pathway) in the frontal cortex (Romero et al. 2008), a primary location of dysfunction in both schizophrenia and depression (Koenigs and Grafman 2009; Lewis and Sweet 2009).”
Regional, circuit and network heterogeneity of brain abnormalities in psychiatric disorders
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“The right PFC showed 21% overlap in MDD cases, whereas the left PFC showed 14–15% overlap in BP. Extensive literature implicates lateral PFC dysfunction in affective disorders 48,50,51 , and the dorsolateral PFC is a popular brain stimulation target in both MDD 52 and BP 53 .”
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Olfaction as a marker for depression
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“In particular, an important role of rACC/VMPFC was proposed in emotional control, especially regarding negative affect as well as in self-awareness and self-reflection (Koenigs and Grafman, 2009).”
BackgroundThe Dynamic Duo: Combining noninvasive brain stimulation with cognitive interventions
Sathappan, A. V., Luber, B. M., & Lisanby, S. H. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.10.006 · Cited by 234
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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…”
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“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
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Optogenetic dissection of medial prefrontal cortex circuitry
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“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…”
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“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
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Microglia of Prefrontal White Matter in Suicide
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“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.”
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“…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].”
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“…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
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“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].”
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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 202
Why estrogens matter for behavior and brain health
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“Brainregions often implicated in depression include the ACC, dorsolateral prefrontal cortex, dorsomedial prefrontal cortex, amygdala, and hippocampus, which together form the frontolimbic “emotion processing” circuitry (92, 126, 155).”
Noninvasive brain stimulation treatments for addiction and major depression
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“modulates the effortful control of negative emotion [39], whereas”
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“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].”
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“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 192
“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 178
“…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 173
“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
“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 166
“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 164
“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
“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
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
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 170
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
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 159
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
“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
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 146
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
“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
“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 141
Ellis, M. J., Leddy, J. J., & Willer, B. S. (2016) · Frontiers in Neurology · doi:10.3389/fneur.2016.00136 · Cited by 134
Caldieraro, M. A., & Cassano, P. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.09.048 · Cited by 136
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 143
“…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
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
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 131
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 127
“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
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
“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 130
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 122
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
“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
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
“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
To do it now or later: The cognitive mechanisms and neural substrates underlying procrastination
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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
“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 117
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 115
“…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
“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
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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
“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).”
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“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
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“…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
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 103
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“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
Metadata
- 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 (medical) › 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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