Journal of Neuroscience
April 15, 1997
Bita Moghaddam, Barbara W. Adams, Anita Verma et al.
1,813 citations
Low doses of the NMDA receptor antagonist ketamine (10, 20, and 30 mg/kg) increase glutamate outflow in the rat prefrontal cortex (PFC), suggesting enhanced glutamatergic neurotransmission at non-NMDA receptors. An anesthetic dose (200 mg/kg) decreases glutamate levels, while an intermediate dose (50 mg/kg) has no effect. Ketamine at 30 mg/kg also increases dopamine release in the PFC, an effect blocked by intra-PFC application of the AMPA/kainate receptor antagonist CNQX. Systemic pretreatment with the AMPA/kainate receptor antagonist LY293558 ameliorates ketamine-induced dopamine release and impairment of spatial delayed alternation, a PFC-sensitive cognitive task. Ketamine may disrupt PFC dopaminergic neurotransmission and cognitive functions partly by increasing glutamate release and stimulating postsynaptic non-NMDA glutamate receptors.
Journal of Neuroscience
March 2, 2011
Robert Leech, Salwa Kamourieh, Christian F. Beckmann et al.
801 citations
The posterior cingulate cortex (PCC), a core region of the default mode network (DMN), shows distinct roles in attention depending on its dorsal and ventral parts. Using fMRI during a working-memory task, standard subtraction analysis showed overall deactivation with increasing difficulty. However, dual-regression functional connectivity revealed a dissociation: the ventral PCC reduced integration with the DMN and anticorrelation with the cognitive control network (CCN) as task demands rose, while the dorsal PCC increased DMN integration and anticorrelation with the CCN. At rest, the dorsal PCC connected with both DMN and attentional networks. These results indicate the PCC supports internally directed thought at low demands and that the dorsal PCC modulates dynamic interactions between networks for attention allocation.
Journal of Neuroscience
March 7, 2012
Gustavo Deco, Viktor Jirsa
778 citations
The brain's ongoing activity at rest, in the absence of tasks or stimulation, is highly structured into spatiotemporal patterns known as resting state networks, which exhibit low-frequency fluctuations below 0.1 Hz. Using a global spiking attractor network model that incorporates realistic neuroanatomical connectivity from diffusion tensor imaging, the authors demonstrate that resting state functional connectivity quantitatively matches human experimental data when the brain network operates at the edge of instability. Under these conditions, slow fluctuations emerge as structured noise around a stable low firing equilibrium, shaped by latent multistable attractors inherent in the neuroanatomical connectivity.
Journal of Neuroscience
October 4, 2017
Melanie Boly, Marcello Massimini, Naotsugu Tsuchiya et al.
591 citations
The role of the frontal cortex in consciousness is debated. This Perspective critically reviews clinical and neuroimaging evidence for the involvement of the front versus the back of the cortex in specifying conscious contents and discusses promising research avenues.
Journal of Neuroscience
November 18, 2009
Angela R. Laird, Simon B. Eickhoff, Karl Li et al.
577 citations
The default mode network (DMN) is a set of brain regions active at rest and less active during many tasks, but these regions also show task-related increases. By combining activation likelihood estimation meta-analysis with the BrainMap database, core DMN regions were identified and their functional heterogeneity examined. Meta-analytic coactivation maps showed each region connects with both DMN and non-DMN areas. Behavioral domain analysis revealed that DMN subnetworks are differentially specialized: affective, perceptual, and motor-processing cliques were identified. The results provide a connectivity model of DMN interactions during diverse tasks.
Journal of Neuroscience
January 19, 2005
Olaf Blanke, Christine Mohr, Christoph M. Michel et al.
573 citations
The temporoparietal junction (TPJ) is crucial for the conscious experience of the self as spatially united with the body. Using evoked potential mapping, the TPJ was selectively activated 330-400 milliseconds after stimulus onset when healthy volunteers imagined themselves in the position and visual perspective typical of out-of-body experiences (OBEs). Transcranial magnetic stimulation (TMS) over the TPJ at this time impaired mental transformation of one's own body but not of external objects. In an epileptic patient with OBEs originating from the TPJ, partial activation of the seizure focus occurred during mental transformations mimicking her OBE perceptions. These findings suggest that impaired processing at the TPJ may lead to pathological selves such as OBEs.
Journal of Neuroscience
August 1, 1988
Elizabeth O’hearn, Giuseppe Battaglia, Eb de Souza et al.
546 citations
Two amphetamine derivatives, MDA and MDMA, cause lasting damage to serotonin-producing nerve fibers in the rat brain. Two weeks after repeated high doses, serotonin axons throughout the forebrain are profoundly lost, while dopamine and norepinephrine axons remain intact. The damage is selective to fine axon terminals; thicker fibers and the cell bodies in the raphe nuclei survive. Some brain regions, such as the hippocampus and parts of the neocortex, show partial sparing. Swollen and fragmented axons observed shortly after treatment confirm ongoing degeneration. MDA produces greater loss of serotonin axons than MDMA at the same dose. The findings establish that these drugs are toxic to serotonin axon terminals and cause long-term denervation of the forebrain.
Journal of Neuroscience
March 23, 2011
Carlo Sestieri, Maurizio Corbetta, Gian Luca Romani et al.
545 citations
The default mode network (DMN) is not functionally uniform during episodic memory retrieval. Using fMRI, parietal regions inside and outside the DMN were examined. Memory retrieval activated posterior DMN nodes, especially the angular gyrus, and also separate anterior/dorsal parietal regions outside the DMN. DMN regions responded sooner, while non-DMN regions showed sustained activity until a memory judgment. A parahippocampal region with strong resting-state connectivity to parietal DMN showed similar task-evoked activity. DMN parietal regions directly supported memory retrieval; non-DMN regions were involved in postretrieval decision-making. A dissociation within the DMN emerged: angular gyrus and posterior cingulate/precuneus were activated, but medial prefrontal cortex was deactivated, demonstrating functional heterogeneity.
Journal of Neuroscience
September 18, 2013
Matthew J. Brookes, David Errtizoe, Ben Sessa et al.
501 citations
Psychedelic drugs like psilocybin produce profound changes in consciousness by desynchronizing ongoing oscillatory rhythms in the cortex. Using magnetoencephalography in healthy participants, psilocybin reduced spontaneous cortical oscillatory power from 1 to 50 Hz in posterior association cortices and from 8 to 100 Hz in frontal association cortices, with large decreases in default-mode network areas. Low-level visually induced and motor-induced gamma-band oscillations were unaffected, suggesting some basic oscillatory activity is preserved. Dynamic causal modeling indicated that posterior cingulate cortex desynchronization results from increased excitability of deep-layer pyramidal neurons rich in 5-HT 2A receptors.
Journal of Neuroscience
October 21, 2009
Antoine Lutz, Heleen A. Slagter, Nancy B. Rawlings et al.
499 citations
Three months of intensive meditation training improved the ability to sustain attention, as measured by dichotic listening task performance and electroencephalography. Training reduced variability in attentional processing of target tones, shown by enhanced theta-band phase consistency of neural responses over anterior brain areas and reduced reaction time variability. Individuals with the greatest increase in neural response consistency showed the largest decrease in behavioral response variability. Reduced variability in neural processing also occurred for unattended deviant tones, suggesting meditation affects both distracter and target processing, possibly by enhancing entrainment of neuronal oscillations to sensory input rhythms.
Journal of Neuroscience
July 1, 1999
Ramesh Srinivasan, D. Patrick Russell, Gerald M. Edelman et al.
438 citations
During binocular rivalry, where each eye sees a different image and perception alternates between them, the brain activity corresponding to the consciously perceived image shows increased synchronization. Red vertical and blue horizontal gratings were presented to each eye, each flickering at a distinct frequency. Magnetoencephalography recorded stronger steady-state magnetic fields at the frequency of the perceived grating over occipital, temporal, and frontal cortices. Coherence analysis revealed increased interhemispheric and intrahemispheric synchronization at the stimulus frequency when that stimulus was perceived. The results demonstrate a direct correlation between conscious perception and synchronous activity of large populations of neocortical neurons.
Journal of Neuroscience
March 12, 2014
Aaron Kucyi, Massieh Moayedi, Irit Weissman‐fogel et al.
390 citations
In patients with chronic pain, rumination—repetitive focus on discomfort—is linked to altered functional connectivity in the brain's default mode network. In a study of 17 patients with temporomandibular disorder and 17 matched healthy controls, those with chronic pain showed enhanced connectivity between the medial prefrontal cortex and other default mode network regions, including the posterior cingulate cortex and precuneus. Among patients, greater rumination about pain correlated with stronger connectivity between the medial prefrontal cortex and the posterior cingulate cortex, precuneus, retrosplenial cortex, medial thalamus, and periaqueductal gray. These results suggest that communication within the default mode network and with the descending pain modulatory system underlies the degree of rumination about chronic pain.
Journal of Neuroscience
October 31, 2012
Micah Allen, Martin Dietz, Karina S. Blair et al.
389 citations
A six-week randomized trial compared mindfulness training to an active control condition in healthy adults. Both groups improved on a response-inhibition task, but only the mindfulness group showed reduced emotional conflict on an affective Stroop task. The mindfulness group also showed greater dorsolateral prefrontal cortex activity during executive processing, suggesting increased use of top-down control. No overall group differences emerged for negative affect-related reaction times or brain responses. However, participants who practiced mindfulness the most showed improved response inhibition and greater recruitment of dorsal anterior cingulate cortex, medial prefrontal cortex, and right anterior insula during negative-valence processing. The findings indicate that mindfulness training engages distinct neural mechanisms at progressive stages and that optimal application may depend on context.
Journal of Neuroscience
June 19, 2013
Michael Kometer, André Schmidt, Lutz Jäncke et al.
357 citations
Psilocybin, a serotonergic hallucinogen, strongly decreased prestimulus parieto-occipital alpha power and reduced N170 visual-evoked potentials in healthy humans, effects linked to visual perceptual alterations including hallucinations. These changes were blocked by pretreatment with the 5-HT2A receptor antagonist ketanserin, indicating that activation of 5-HT2A receptors by psilocybin modulates visual processing by overwhelming stimulus-driven cortical excitation with spontaneous neuronal excitation via alpha oscillations. The reduction in N170 potentials may be a key mechanism underlying 5-HT2A receptor-mediated visual hallucinations, relevant not only to psilocybin-induced states but also to acute hallucinatory states in psychiatric disorders such as schizophrenia and Parkinson's disease.
Journal of Neuroscience
July 1, 1998
Jessica E. Malberg, Lewis S. Seiden
344 citations
Small changes in ambient temperature alter core body temperature in rats given MDMA, and those temperature shifts influence the drug's neurotoxicity. Rats treated with MDMA at 20 or 22°C showed a drop in core temperature and no detectable damage to serotonin nerve endings in brain regions examined. At 26–30°C, core temperature rose and neurotoxicity appeared in the frontal cortex, somatosensory cortex, hippocampus, and striatum, with damage severity linked to core temperature. Saline-treated rats showed no temperature changes across the same ambient conditions. These findings suggest ambient temperature strongly affects MDMA's toxicity and thermoregulation, with implications for human use where fatal hyperthermia occurs.
Journal of Neuroscience
June 15, 1999
George Hatzidimitriou, Una D. Mccann, George A. Ricaurte
338 citations
Seven years after treatment with MDMA (Ecstasy), squirrel monkeys still showed abnormal brain serotonin innervation patterns, though deficits in some regions were less severe than those observed at 18 months. No loss of serotonin nerve cell bodies in the rostral raphe nuclei was found, indicating that the abnormal patterns are not due to the loss of a particular cell group. Factors influencing recovery of injured serotonin axons include the distance of the affected terminal field from the raphe nuclei, the degree of initial injury, and possibly proximity to myelinated fiber tracts. Additional studies are needed to understand these factors and whether findings apply to humans.
Journal of Neuroscience
December 15, 2001
Raúl Martín‐Ruiz, M. Victoria Puig, Pau Celada et al.
335 citations
The hallucinogen DOI suppresses the firing rate of most serotonergic neurons in the dorsal raphe nucleus and reduces serotonin release in the medial prefrontal cortex to 33% of baseline, effects mediated by 5-HT2A receptors and reversed by a GABA-A antagonist. However, locally applied DOI in the medial prefrontal cortex increases serotonin release to 164% of baseline through AMPA receptors, not NMDA receptors. DOI also increases the firing rate of a subgroup of serotonergic neurons, indicating enhanced output of pyramidal neurons. Pyramidal neurons coexpress 5-HT1A and 5-HT2A receptors, and DOI disrupts the balance between excitatory and inhibitory inputs, leading to increased activity that may mediate its hallucinogenic action.
Journal of Neuroscience
October 24, 2007
Francis Rodriguez Bambico, Noam Katz, Guy Debonnel et al.
325 citations
Low doses of the cannabinoid CB1 receptor agonist WIN55,212-2 produce antidepressant-like effects in rats, as measured by the forced-swim test. This effect depends on CB1 receptors and the serotonin system, as it is blocked by the CB1 antagonist rimonabant and by serotonin depletion. Electrophysiology shows that low doses of WIN55,212-2 increase serotonin neuron firing in the dorsal raphe nucleus via a CB1-dependent mechanism, while high doses decrease firing through a CB1-independent mechanism and lack antidepressant effects. The enhancement of serotonin activity requires the ventromedial prefrontal cortex, as local microinjection there mimics the antidepressant effect, whereas lateral prefrontal cortex involvement is not needed.
Journal of Neuroscience
October 1, 2003
Javier González‐maeso, Tony Yuen, Barbara J. Ebersole et al.
295 citations
Different drugs that activate the same serotonin receptor (5-HT2AR) can produce distinct patterns of gene expression in the brain, which correspond to different behavioral effects. The hallucinogens DOI and LSD triggered a head-twitch response in mice and produced similar changes in the somatosensory cortex transcriptome, while the nonhallucinogenic drug lisuride did not cause this behavior and generated a different transcriptome fingerprint. These effects were absent in mice lacking the 5-HT2AR, confirming the receptor's role. The findings suggest that drugs acting at the same receptor can induce unique cellular response patterns in the living brain, detectable through transcriptome analysis.
Journal of Neuroscience
August 1, 1995
Christina Weide Fischer, George Hatzidimitriou, J Wlos et al.
269 citations
MDMA destroys serotonin axons in the brain. After injury, these axons can regrow, but the new connections are often abnormal. In rats and squirrel monkeys studied 12–18 months after MDMA exposure, some brain regions remained denervated while others became reinnervated or even hyperinnervated. Distant targets like the dorsal neocortex stayed denervated, whereas proximal targets such as the amygdala and hypothalamus recovered. Longer or more highly arborized axons had lower recovery probability. This lasting reorganization of serotonin projections may have implications for humans who use MDMA recreationally.
Journal of Neuroscience
November 30, 2020
Danilo de Gregorio, Argel Aguilar‐valles, Katrin H. Preller et al.
258 citations
A renewed interest in hallucinogens for treating psychiatric disorders has emerged. Preclinical and clinical studies have confirmed ketamine's efficacy for depression. Emerging evidence points to psilocybin and LSD's therapeutic properties and their ability to modulate functional brain connectivity. MDMA, an entactogen, has shown usefulness for post-traumatic stress disorder. This review summarizes the pharmacology of hallucinogenic compounds, highlighting differences between psychedelic and nonpsychedelic hallucinogens and entactogens, and describes their behavioral effects in animals and humans. Together, these data substantiate the potential of these compounds for treating mental diseases.
Journal of Neuroscience
November 2, 2016
Charles F. Zorumski, Yukitoshi Izumi, Steven Mennerick
252 citations
Ketamine, a dissociative anesthetic, has drawn attention for both its psychosis-like effects and its rapid antidepressant action. While ketamine clearly inhibits NMDARs and may preferentially affect interneurons, recent research questions whether NMDAR blockade is essential for its mood-elevating effects. This viewpoint reviews evidence that NMDARs are important triggers for some psychiatric effects, but the antidepressant trigger might be unrelated to NMDARs. The evolving understanding of ketamine's mechanisms holds promise for disentangling and treating the biology of depression and psychosis.
Journal of Neuroscience
August 19, 2015
Suresh Muthukumaraswamy, Alexander D. Shaw, Laura E. Jackson et al.
244 citations
Subanesthetic doses of ketamine, similar to those used in antidepressant studies, increase anterior theta and gamma power but decrease posterior theta, delta, and alpha power, as shown by magnetoencephalographic recordings. Dynamic causal modeling revealed a decrease in NMDA and AMPA-mediated frontal-to-parietal connectivity, with AMPA-mediated changes persisting up to 50 minutes after infusion ceased, even after perceptual distortions had ended. A decrease in gain of parietal pyramidal cells correlated with participants' self-reports of blissful state. These alterations in frontoparietal connectivity patterns may be important in generating the antidepressant response to ketamine.
Journal of Neuroscience
August 13, 2014
S. R. Jilka, G. Scott, T. Ham et al.
242 citations
Interactions between the Salience Network (SN) and the Default Mode Network (DMN) are important for cognitive control. In healthy subjects, functional connectivity between a key SN node (right anterior insula) and the DMN transiently increased during motor response inhibition and switching. This change was absent in traumatic brain injury (TBI) patients with impaired cognitive control. The amount of SN tract damage negatively correlated with connectivity between the networks, a finding replicated in a second TBI group. Results indicate that SN damage impairs dynamic network coupling and support a model where the SN signals the DMN to reduce activity during externally focused attention.
Journal of Neuroscience
January 8, 2014
Peter J. Hellyer, Murray Shanahan, Gregory Scott et al.
225 citations
During an attentionally demanding task, brain activity becomes more synchronized and less variable over time compared to rest. This shift is linked to increased activity in the frontoparietal control/dorsal attention network and decreased activity in the default mode network. A computational model confirmed that activating the frontoparietal network increases synchrony and reduces variability, while activating the default mode network does the opposite. The balance between these networks may control how the brain shifts between an unfocused, exploratory state with high variability and a focused, constrained state with low variability.