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Georg Northoff - One of the best experts on this subject based on the ideXlab platform.

  • attentional modulation of emotional stimulus processing in patients with major depression alterations in Prefrontal cortical regions
    Neuroscience Letters, 2009
    Co-Authors: Felix Bermpohl, Martin Walter, Bastian Sajonz, Christian Lucke, Claudia Hagele, Philipp Sterzer, Mazda Adli, Andreas Heinz, Georg Northoff
    Abstract:

    Patients with depression show an impaired ability to modulate emotional states and to process positive emotional information. Here we examined expectancy-induced modulation of emotional picture processing in major depression. We hypothesized alterations in the medial Prefrontal Cortex. During fMRI, 15 depressed and 21 healthy control subjects passively viewed affective photographs. Half of the pictures were preceded by an expectancy cue signaling whether an emotionally salient or neutral picture would follow. The contrast ‘cued versus uncued emotional picture viewing’ was used to study modulation of emotional picture processing by preceding attention. Healthy individuals showed enhanced activation in the Dorsomedial Prefrontal Cortex and decreased activation in the dorsolateral Prefrontal Cortex during cued compared to uncued emotional picture perception. The group comparison revealed that these modulatory effects were significantly attenuated in depressed patients. This attenuation was particularly observed in the positive compared to the negative picture condition and tended to normalize in the Dorsomedial Prefrontal Cortex after remission of symptoms. Altered Prefrontal modulation in depression may contribute to impaired affect modulation and related clinical symptoms, such as anhedonia.

  • preceding attention and the Dorsomedial Prefrontal Cortex process specificity versus domain dependence
    Human Brain Mapping, 2009
    Co-Authors: Martin Walter, Bernhard Bogerts, Christine Wiebking, Michael Rotte, Claus Tempelmann, Hansjochen Heinze, Christian Matthia, Georg Northoff
    Abstract:

    The Dorsomedial Prefrontal Cortex (DMPFC) has been shown to be involved in attending differ- ent states, all including a strong emotional component. It remains unclear, though, whether neural activity in the DMPFC is predominantly determined by either a particular domain, as emotional stimuli, or by a specific process, as attention. Here, we used functional magnetic resonance imaging to test the alternative hypotheses of domain- versus process-specificity in DMPFC. Subjects had to perceive pictures from three different domains, sexual, emotional, and neutral stimuli, in both a nonattended, i.e., unexpected, and attended, i.e., expected mode. Our results show DMPFC activation during attended, i.e., expected stimulus perception when compared with nonattended, i.e., unexpected stimuli perception. DMPFC activation and corresponding behavioral changes (reaction time, subjective ratings) were observed in all three domains, sexual, emotional, and neutral stimuli. As opposed to those process-specific effects that were found pre- dominantly in posterior DMPFC, a process by domain interaction was found to be characteristic for more anterior parts of the DMPFC. Taken together, our findings favour the hypothesis that neural activity in the posterior DMPFC is determined by a specific process, i.e., attending stimuli, and thus characterized by process-specificity rather than by a particular domain, i.e., sexual, emotional, or neutral stimuli, reflecting domain-specificity. This suggests that the anterior and posterior DMPFC is involved in the process of attending mental states while remaining more (posterior DMPFC) or less (anterior DMPFC) independent of the type or domain of the respective stimulus. Hum Brain Mapp 30:312-326, 2009. V C 2007 Wiley-Liss, Inc.

  • s ketamine and gaba a receptor interaction in humans an exploratory study with i 123 iomazenil spect
    Human Psychopharmacology-clinical and Experimental, 2008
    Co-Authors: Alexander Heinzel, Rainer Steinke, Thorsten D Poeppel, Oliver Grosser, Hans Otto, Bernhard Bogerts, Georg Northoff
    Abstract:

    Objective We aimed to probe for regional cerebral effects of S-ketamine on in vivo GABA-A-receptor binding in healthy human subjects. Methods We investigated I-123-iomazenil SPECT before, during and after administration of S-ketamine in a blinded placebo-controlled study design (n = 12 in both groups). Analyses of SPECT were performed with voxel-based statistical parametric mapping (SPM), and statistical comparisons were made between the groups. We also assessed biochemical and behavioural changes during S-ketamine infusion. Results S-ketamine induced positive and negative symptoms measured by the Brief Psychiatric Rating scale (BPRS). It increased the cortisol and prolactin levels. Image analysis revealed significantly decreased I-123-iomazenil binding in bilateral Dorsomedial Prefrontal Cortex during S-ketamine administration when compared to placebo. Conclusion Our study delivers preliminary evidence for an in vivo interaction of S-ketamine with GABA-A-receptors in human Dorsomedial Prefrontal Cortex. Copyright © 2008 John Wiley & Sons, Ltd.

  • Distinguishing specific sexual and general emotional effects in fMRI-subcortical and cortical arousal during erotic picture viewing.
    NeuroImage, 2008
    Co-Authors: Martin Walter, Bernhard Bogerts, Michael Rotte, Kolja Schiltz, Felix Bermpohl, Claus Tempelmann, Hansjochen Heinze, Harold Mouras, Georg Northoff
    Abstract:

    Sexual activity involves excitement with high arousal and pleasure as typical features of emotions. Brain activations specifically related to erotic feelings and those related to general emotional processing are therefore hard to disentangle. Using fMRI in 21 healthy subjects (11 males and 10 females), we investigated regions that show activations specifically related to the viewing of sexually intense pictures while controlling for general emotional arousal (GEA) or pleasure. Activations in the ventral striatum and hypothalamus were found to be modulated by the stimulus' specific sexual intensity (SSI) while activations in the anterior cingulate Cortex were associated with an interaction between sexual intensity and emotional valence. In contrast, activation in other regions like the Dorsomedial Prefrontal Cortex, the mediodorsal thalamus and the amygdala was associated only with a general emotional component during sexual arousal. No differences were found in these effects when comparing females and males. Our findings demonstrate for the first time neural differentiation between emotional and sexual components in the neural network underlying sexual arousal.

  • reciprocal modulation and attenuation in the Prefrontal Cortex an fmri study on emotional cognitive interaction
    Human Brain Mapping, 2004
    Co-Authors: Alexander Heinzel, Georg Northoff, Felix Bermpohl, Robert Niese, Andrea Pfennig, Alvaro Pascualleone, Gottfried Schlaug
    Abstract:

    Everyday and clinical experience demonstrate strong interactions between emotions and cognitions. Nevertheless the neural correlates underlying emotional- cognitive interaction remain unclear. Using event- related fMRI, we investigated BOLD-signal increases and decreases in medial and lateral Prefrontal cortical regions during emotional and non-emotional judgment of photographs taken from the International Affective Picture System (IAPS). Emotional and non-emotional judgment conditions were compared to each other as well as with baseline allowing for distinction between relative signal changes (comparison between conditions) and true signal changes (referring to baseline). We have found that: (1) both emotional and non-emotional judgment of IAPS pictures were characterized by signal increases in ventrally and dorsally located lateral Prefrontal cortical areas and concurrent signal decreases in ventro- and Dorsomedial Prefrontal Cortex; (2) direct comparison between emotional and non-emotional judgment showed relative signal increases in ventro- and Dorsomedial Prefrontal Cortex, and in contrast, relative signal increases were detected in ventrally and dorsally located lateral Prefrontal cortical areas when comparing non-emotional to emotional judgment; and (3) as shown in separate comparisons with baseline, these relative signal changes were due to smaller signal decreases in ventro- and Dorsomedial Prefrontal Cortex and smaller signal increases in ventrally and dorsally located lateral Prefrontal cortical areas during emotional judgment. Therefore, the emotional load of a cognitive task lead to both less deactivation of medial Prefrontal regions and, at the same time, less activation of lateral Prefrontal regions. Analogous patterns of reciprocal modulation and attenuation have previously been described for other cortical regions such as visual and auditory areas. Reciprocal modulation and attenuation in medial and lateral Prefrontal Cortex might constitute the neurophysiologic basis for emotional-cognitive interaction as observed in both healthy and psychiatric subjects. Hum. Brain Mapp. 21:202-212, 2004. © 2004 Wiley-Liss, Inc.

Martin Walter - One of the best experts on this subject based on the ideXlab platform.

  • attentional modulation of emotional stimulus processing in patients with major depression alterations in Prefrontal cortical regions
    Neuroscience Letters, 2009
    Co-Authors: Felix Bermpohl, Martin Walter, Bastian Sajonz, Christian Lucke, Claudia Hagele, Philipp Sterzer, Mazda Adli, Andreas Heinz, Georg Northoff
    Abstract:

    Patients with depression show an impaired ability to modulate emotional states and to process positive emotional information. Here we examined expectancy-induced modulation of emotional picture processing in major depression. We hypothesized alterations in the medial Prefrontal Cortex. During fMRI, 15 depressed and 21 healthy control subjects passively viewed affective photographs. Half of the pictures were preceded by an expectancy cue signaling whether an emotionally salient or neutral picture would follow. The contrast ‘cued versus uncued emotional picture viewing’ was used to study modulation of emotional picture processing by preceding attention. Healthy individuals showed enhanced activation in the Dorsomedial Prefrontal Cortex and decreased activation in the dorsolateral Prefrontal Cortex during cued compared to uncued emotional picture perception. The group comparison revealed that these modulatory effects were significantly attenuated in depressed patients. This attenuation was particularly observed in the positive compared to the negative picture condition and tended to normalize in the Dorsomedial Prefrontal Cortex after remission of symptoms. Altered Prefrontal modulation in depression may contribute to impaired affect modulation and related clinical symptoms, such as anhedonia.

  • preceding attention and the Dorsomedial Prefrontal Cortex process specificity versus domain dependence
    Human Brain Mapping, 2009
    Co-Authors: Martin Walter, Bernhard Bogerts, Christine Wiebking, Michael Rotte, Claus Tempelmann, Hansjochen Heinze, Christian Matthia, Georg Northoff
    Abstract:

    The Dorsomedial Prefrontal Cortex (DMPFC) has been shown to be involved in attending differ- ent states, all including a strong emotional component. It remains unclear, though, whether neural activity in the DMPFC is predominantly determined by either a particular domain, as emotional stimuli, or by a specific process, as attention. Here, we used functional magnetic resonance imaging to test the alternative hypotheses of domain- versus process-specificity in DMPFC. Subjects had to perceive pictures from three different domains, sexual, emotional, and neutral stimuli, in both a nonattended, i.e., unexpected, and attended, i.e., expected mode. Our results show DMPFC activation during attended, i.e., expected stimulus perception when compared with nonattended, i.e., unexpected stimuli perception. DMPFC activation and corresponding behavioral changes (reaction time, subjective ratings) were observed in all three domains, sexual, emotional, and neutral stimuli. As opposed to those process-specific effects that were found pre- dominantly in posterior DMPFC, a process by domain interaction was found to be characteristic for more anterior parts of the DMPFC. Taken together, our findings favour the hypothesis that neural activity in the posterior DMPFC is determined by a specific process, i.e., attending stimuli, and thus characterized by process-specificity rather than by a particular domain, i.e., sexual, emotional, or neutral stimuli, reflecting domain-specificity. This suggests that the anterior and posterior DMPFC is involved in the process of attending mental states while remaining more (posterior DMPFC) or less (anterior DMPFC) independent of the type or domain of the respective stimulus. Hum Brain Mapp 30:312-326, 2009. V C 2007 Wiley-Liss, Inc.

  • Distinguishing specific sexual and general emotional effects in fMRI-subcortical and cortical arousal during erotic picture viewing.
    NeuroImage, 2008
    Co-Authors: Martin Walter, Bernhard Bogerts, Michael Rotte, Kolja Schiltz, Felix Bermpohl, Claus Tempelmann, Hansjochen Heinze, Harold Mouras, Georg Northoff
    Abstract:

    Sexual activity involves excitement with high arousal and pleasure as typical features of emotions. Brain activations specifically related to erotic feelings and those related to general emotional processing are therefore hard to disentangle. Using fMRI in 21 healthy subjects (11 males and 10 females), we investigated regions that show activations specifically related to the viewing of sexually intense pictures while controlling for general emotional arousal (GEA) or pleasure. Activations in the ventral striatum and hypothalamus were found to be modulated by the stimulus' specific sexual intensity (SSI) while activations in the anterior cingulate Cortex were associated with an interaction between sexual intensity and emotional valence. In contrast, activation in other regions like the Dorsomedial Prefrontal Cortex, the mediodorsal thalamus and the amygdala was associated only with a general emotional component during sexual arousal. No differences were found in these effects when comparing females and males. Our findings demonstrate for the first time neural differentiation between emotional and sexual components in the neural network underlying sexual arousal.

  • pedophilia is linked to reduced activation in hypothalamus and lateral Prefrontal Cortex during visual erotic stimulation
    Biological Psychiatry, 2007
    Co-Authors: Martin Walter, Bernhard Bogerts, Joachim Witzel, Christine Wiebking, Udo Gubka, Michael Rotte, Kolja Schiltz, Felix Bermpohl, Claus Tempelmann, Hansjochen Heinze
    Abstract:

    Background Although pedophilia is of high public concern, little is known about underlying neural mechanisms. Although pedophilic patients are sexually attracted to prepubescent children, they show no sexual interest toward adults. This study aimed to investigate the neural correlates of deficits of sexual and emotional arousal in pedophiles. Methods Thirteen pedophilic patients and 14 healthy control subjects were tested for differential neural activity during visual stimulation with emotional and erotic pictures with functional magnetic resonance imaging. Results Regions showing differential activations during the erotic condition comprised the hypothalamus, the periaqueductal gray, and dorsolateral Prefrontal Cortex, the latter correlating with a clinical measure. Alterations of emotional processing concerned the amygdala–hippocampus and Dorsomedial Prefrontal Cortex. Conclusions Hypothesized regions relevant for processing of erotic stimuli in healthy individuals showed reduced activations during visual erotic stimulation in pedophilic patients. This suggests an impaired recruitment of key structures that might contribute to an altered sexual interest of these patients toward adults.

Felix Bermpohl - One of the best experts on this subject based on the ideXlab platform.

  • attentional modulation of emotional stimulus processing in patients with major depression alterations in Prefrontal cortical regions
    Neuroscience Letters, 2009
    Co-Authors: Felix Bermpohl, Martin Walter, Bastian Sajonz, Christian Lucke, Claudia Hagele, Philipp Sterzer, Mazda Adli, Andreas Heinz, Georg Northoff
    Abstract:

    Patients with depression show an impaired ability to modulate emotional states and to process positive emotional information. Here we examined expectancy-induced modulation of emotional picture processing in major depression. We hypothesized alterations in the medial Prefrontal Cortex. During fMRI, 15 depressed and 21 healthy control subjects passively viewed affective photographs. Half of the pictures were preceded by an expectancy cue signaling whether an emotionally salient or neutral picture would follow. The contrast ‘cued versus uncued emotional picture viewing’ was used to study modulation of emotional picture processing by preceding attention. Healthy individuals showed enhanced activation in the Dorsomedial Prefrontal Cortex and decreased activation in the dorsolateral Prefrontal Cortex during cued compared to uncued emotional picture perception. The group comparison revealed that these modulatory effects were significantly attenuated in depressed patients. This attenuation was particularly observed in the positive compared to the negative picture condition and tended to normalize in the Dorsomedial Prefrontal Cortex after remission of symptoms. Altered Prefrontal modulation in depression may contribute to impaired affect modulation and related clinical symptoms, such as anhedonia.

  • Distinguishing specific sexual and general emotional effects in fMRI-subcortical and cortical arousal during erotic picture viewing.
    NeuroImage, 2008
    Co-Authors: Martin Walter, Bernhard Bogerts, Michael Rotte, Kolja Schiltz, Felix Bermpohl, Claus Tempelmann, Hansjochen Heinze, Harold Mouras, Georg Northoff
    Abstract:

    Sexual activity involves excitement with high arousal and pleasure as typical features of emotions. Brain activations specifically related to erotic feelings and those related to general emotional processing are therefore hard to disentangle. Using fMRI in 21 healthy subjects (11 males and 10 females), we investigated regions that show activations specifically related to the viewing of sexually intense pictures while controlling for general emotional arousal (GEA) or pleasure. Activations in the ventral striatum and hypothalamus were found to be modulated by the stimulus' specific sexual intensity (SSI) while activations in the anterior cingulate Cortex were associated with an interaction between sexual intensity and emotional valence. In contrast, activation in other regions like the Dorsomedial Prefrontal Cortex, the mediodorsal thalamus and the amygdala was associated only with a general emotional component during sexual arousal. No differences were found in these effects when comparing females and males. Our findings demonstrate for the first time neural differentiation between emotional and sexual components in the neural network underlying sexual arousal.

  • pedophilia is linked to reduced activation in hypothalamus and lateral Prefrontal Cortex during visual erotic stimulation
    Biological Psychiatry, 2007
    Co-Authors: Martin Walter, Bernhard Bogerts, Joachim Witzel, Christine Wiebking, Udo Gubka, Michael Rotte, Kolja Schiltz, Felix Bermpohl, Claus Tempelmann, Hansjochen Heinze
    Abstract:

    Background Although pedophilia is of high public concern, little is known about underlying neural mechanisms. Although pedophilic patients are sexually attracted to prepubescent children, they show no sexual interest toward adults. This study aimed to investigate the neural correlates of deficits of sexual and emotional arousal in pedophiles. Methods Thirteen pedophilic patients and 14 healthy control subjects were tested for differential neural activity during visual stimulation with emotional and erotic pictures with functional magnetic resonance imaging. Results Regions showing differential activations during the erotic condition comprised the hypothalamus, the periaqueductal gray, and dorsolateral Prefrontal Cortex, the latter correlating with a clinical measure. Alterations of emotional processing concerned the amygdala–hippocampus and Dorsomedial Prefrontal Cortex. Conclusions Hypothesized regions relevant for processing of erotic stimuli in healthy individuals showed reduced activations during visual erotic stimulation in pedophilic patients. This suggests an impaired recruitment of key structures that might contribute to an altered sexual interest of these patients toward adults.

  • reciprocal modulation and attenuation in the Prefrontal Cortex an fmri study on emotional cognitive interaction
    Human Brain Mapping, 2004
    Co-Authors: Alexander Heinzel, Georg Northoff, Felix Bermpohl, Robert Niese, Andrea Pfennig, Alvaro Pascualleone, Gottfried Schlaug
    Abstract:

    Everyday and clinical experience demonstrate strong interactions between emotions and cognitions. Nevertheless the neural correlates underlying emotional- cognitive interaction remain unclear. Using event- related fMRI, we investigated BOLD-signal increases and decreases in medial and lateral Prefrontal cortical regions during emotional and non-emotional judgment of photographs taken from the International Affective Picture System (IAPS). Emotional and non-emotional judgment conditions were compared to each other as well as with baseline allowing for distinction between relative signal changes (comparison between conditions) and true signal changes (referring to baseline). We have found that: (1) both emotional and non-emotional judgment of IAPS pictures were characterized by signal increases in ventrally and dorsally located lateral Prefrontal cortical areas and concurrent signal decreases in ventro- and Dorsomedial Prefrontal Cortex; (2) direct comparison between emotional and non-emotional judgment showed relative signal increases in ventro- and Dorsomedial Prefrontal Cortex, and in contrast, relative signal increases were detected in ventrally and dorsally located lateral Prefrontal cortical areas when comparing non-emotional to emotional judgment; and (3) as shown in separate comparisons with baseline, these relative signal changes were due to smaller signal decreases in ventro- and Dorsomedial Prefrontal Cortex and smaller signal increases in ventrally and dorsally located lateral Prefrontal cortical areas during emotional judgment. Therefore, the emotional load of a cognitive task lead to both less deactivation of medial Prefrontal regions and, at the same time, less activation of lateral Prefrontal regions. Analogous patterns of reciprocal modulation and attenuation have previously been described for other cortical regions such as visual and auditory areas. Reciprocal modulation and attenuation in medial and lateral Prefrontal Cortex might constitute the neurophysiologic basis for emotional-cognitive interaction as observed in both healthy and psychiatric subjects. Hum. Brain Mapp. 21:202-212, 2004. © 2004 Wiley-Liss, Inc.

Rita A Fuchs - One of the best experts on this subject based on the ideXlab platform.

  • interactions of the basolateral amygdala with the dorsal hippocampus and Dorsomedial Prefrontal Cortex regulate drug context induced reinstatement of cocaine seeking in rats
    European Journal of Neuroscience, 2007
    Co-Authors: Rita A Fuchs, Jessica L Eaddy, Guinevere H Bell
    Abstract:

    The basolateral amygdala (BLA), Dorsomedial Prefrontal Cortex (dmPFC) and dorsal hippocampus (DH) are critical elements of the neurocircuitry of drug context-induced reinstatement of cocaine-seeking; however, little is known about functional interactions between these brain regions. The present study tested the hypothesis that serial information processing by the BLA and dmPFC mediates drug context-induced cocaine-seeking, whereas the BLA and DH independently control this behaviour. Rats were trained to self-administer cocaine in a distinct environment (cocaine-paired context) followed by extinction training in a different environment (extinction context). On the test days, rats received unilateral microinfusions of baclofen + muscimol or of vehicle into the BLA and either the contralateral or ipsilateral dmPFC or DH. Cocaine-seeking behaviour (i.e. nonreinforced presses on the cocaine-associated lever) was then assessed in the cocaine-paired and extinction contexts. Following vehicle pretreatment, exposure to the cocaine-paired context reinstated extinguished cocaine-seeking behaviour. BLA-dmPFC asymmetrical inactivation attenuated cocaine-seeking behaviour relative to vehicle treatment; however, this impairment equaled that produced by ipsilateral BLA-dmPFC inactivation. Furthermore, unilateral inactivation of the BLA or dmPFC did not alter this behaviour. BLA-DH asymmetrical inactivation selectively attenuated cocaine-seeking behaviour relative to vehicle treatment whereas ipsilateral or unilateral inactivation of the BLA and DH did not alter this behaviour. These findings indicate that the BLA and DH exhibit sequential information processing within the relapse circuitry. In contrast, interactions between the BLA and dmPFC are more complex and include parallel loops of information processing and/or necessary interhemispheric input from the dmPFC to the BLA, probably in addition to direct intrahemispheric interactions.

  • the role of the Dorsomedial Prefrontal Cortex basolateral amygdala and dorsal hippocampus in contextual reinstatement of cocaine seeking in rats
    Neuropsychopharmacology, 2005
    Co-Authors: Rita A Fuchs, Allison K Evans, Christopher C Ledford, Macon P Parker, Jordan M Case, Ritu H Mehta
    Abstract:

    The present study tested the hypothesis that separate neural substrates mediate cocaine relapse elicited by drug-associated contextual stimuli vs explicit conditioned stimuli (CSs) and cocaine. Specifically, we investigated the involvement of the dorsal hippocampus (DH), basolateral amygdala (BLA), and Dorsomedial Prefrontal Cortex (dmPFC) in contextual reinstatement of cocaine-seeking behavior and the involvement of the DH in explicit CS- and cocaine-induced reinstatement. Rats were trained to self-administer cocaine in a distinct context or in the presence of CSs paired explicitly with cocaine infusions. Responding of context-trained rats was then extinguished in the previously cocaine-paired or an alternate context, whereas responding of explicit CS-trained rats was extinguished in the absence of the CSs. Subsequently, the target brain regions or anatomical control regions were functionally inactivated using tetrodotoxin (0 or 5 ng/side), and cocaine-seeking behavior (ie, nonreinforced responses) was assessed in the cocaine-paired context, in the alternate context, in the presence of the explicit CSs, or following cocaine priming (10 mg/kg, i.p.). DH inactivation abolished contextual, but failed to alter explicit CS- or cocaine-induced, reinstatement of cocaine-seeking behavior. BLA or dmPFC inactivation also abolished contextual reinstatement. Conversely, inactivation of the control brain regions failed to alter contextual reinstatement. In conclusion, the DH, BLA, and dmPFC play critical roles in contextual reinstatement. Previous findings suggest that the BLA is critical for explicit CS-induced, but not cocaine-primed, reinstatement and the dmPFC is critical for both explicit CS-induced and cocaine-primed reinstatement. Thus, distinct but partially overlapping neural substrates mediate context-induced, explicit CS-induced, and cocaine-primed reinstatement of extinguished cocaine-seeking behavior.

Ritu H Mehta - One of the best experts on this subject based on the ideXlab platform.

  • the role of the Dorsomedial Prefrontal Cortex basolateral amygdala and dorsal hippocampus in contextual reinstatement of cocaine seeking in rats
    Neuropsychopharmacology, 2005
    Co-Authors: Rita A Fuchs, Allison K Evans, Christopher C Ledford, Macon P Parker, Jordan M Case, Ritu H Mehta
    Abstract:

    The present study tested the hypothesis that separate neural substrates mediate cocaine relapse elicited by drug-associated contextual stimuli vs explicit conditioned stimuli (CSs) and cocaine. Specifically, we investigated the involvement of the dorsal hippocampus (DH), basolateral amygdala (BLA), and Dorsomedial Prefrontal Cortex (dmPFC) in contextual reinstatement of cocaine-seeking behavior and the involvement of the DH in explicit CS- and cocaine-induced reinstatement. Rats were trained to self-administer cocaine in a distinct context or in the presence of CSs paired explicitly with cocaine infusions. Responding of context-trained rats was then extinguished in the previously cocaine-paired or an alternate context, whereas responding of explicit CS-trained rats was extinguished in the absence of the CSs. Subsequently, the target brain regions or anatomical control regions were functionally inactivated using tetrodotoxin (0 or 5 ng/side), and cocaine-seeking behavior (ie, nonreinforced responses) was assessed in the cocaine-paired context, in the alternate context, in the presence of the explicit CSs, or following cocaine priming (10 mg/kg, i.p.). DH inactivation abolished contextual, but failed to alter explicit CS- or cocaine-induced, reinstatement of cocaine-seeking behavior. BLA or dmPFC inactivation also abolished contextual reinstatement. Conversely, inactivation of the control brain regions failed to alter contextual reinstatement. In conclusion, the DH, BLA, and dmPFC play critical roles in contextual reinstatement. Previous findings suggest that the BLA is critical for explicit CS-induced, but not cocaine-primed, reinstatement and the dmPFC is critical for both explicit CS-induced and cocaine-primed reinstatement. Thus, distinct but partially overlapping neural substrates mediate context-induced, explicit CS-induced, and cocaine-primed reinstatement of extinguished cocaine-seeking behavior.