Annals of the New York Academy of Sciences
March 1, 2008
Giulio Tononi, Christof Koch
615 citations
This review synthesizes recent findings on the neural correlates of consciousness, distinguishing consciousness from other brain functions. It examines global changes in consciousness during sleep, anesthesia, and seizures, then explores paradigms for studying neural correlates of specific conscious percepts, highlighting the roles of different brain regions. Dynamic aspects of neural activity—sustained versus phasic, feedforward versus reentrant, and neural synchronization—are discussed. The review also considers how theoretical analysis of consciousness's fundamental properties can complement neurobiological research.
Annals of the New York Academy of Sciences
December 21, 2018
Heather L. Rusch, Michael Del Rosario, Lisa M. Levison et al.
496 citations
A meta-analysis of 18 trials with 1,654 participants found that mindfulness meditation interventions did not improve sleep quality compared to specific active controls (such as evidence-based sleep treatments) at posttreatment or follow-up, with low strength of evidence. However, compared to nonspecific active controls (time- or attention-matched interventions), mindfulness meditation significantly improved sleep quality at postintervention and follow-up, with moderate strength of evidence. These preliminary findings suggest mindfulness meditation may be effective for some aspects of sleep disturbance, but further research is needed.
Annals of the New York Academy of Sciences
May 1, 2008
396 citations
Spontaneous brain activity, measured during rest, has been proposed as a way to understand brain-behavior relationships, but its value is debated. This review argues that altered states of consciousness—such as sleep, anesthesia, coma, vegetative state, epileptic loss of consciousness, and somnambulism—offer a privileged way to study these links. Early PET studies showed that extremely low or high brain activity often accompanies unconsciousness, but this link is not absolute. Voxel-based analyses consistently found impaired associative frontoparieto-cingulate areas across altered states. Recent fMRI studies reveal structured slow neuronal oscillations and coherent BOLD patterns, especially in the default-mode network, even during unconsciousness. These patterns may reflect default brain connectivity that transcends consciousness, but their functional significance remains unclear.
Annals of the New York Academy of Sciences
December 1, 1995
Jeffrey L. Cummings
362 citations
Frontal-subcortical circuits, originating in the dorsolateral prefrontal cortex, orbitofrontal cortex, and anterior cingulate cortex, provide a framework for understanding the anatomy, biochemistry, and pharmacology of behavior. Circuit-specific marker behaviors include executive dysfunction (dorsolateral prefrontal-subcortical circuit), disinhibition and OCD (orbitofrontal-subcortical circuit), and apathy (medial frontal-subcortical circuit). Environmental dependency is common to all prefrontal-subcortical syndromes and may reflect disruption of working memory. Depression, mania, and psychosis are circuit-related but not circuit-specific. The actions of PCP, LSD, serotonergic antidepressants, anxiolytics, sedative-hypnotics, antipsychotic agents, and ethanol may be partially or primarily mediated through transmitter systems and receptor effects expressed through frontal-subcortical circuits.
Annals of the New York Academy of Sciences
August 1, 2009
Elissa S. Epel, Jennifer Daubenmier, Judith T. Moskowitz et al.
324 citations
Telomere length, a marker of cellular aging, is linked to chronic stress and depression. Psychological stress cognitions, such as threat appraisals and rumination, can prolong stress reactivity and may shorten telomeres. In contrast, mindfulness meditation shifts appraisals from threat to challenge, reduces rumination and stress arousal, and may increase positive arousal states. A review of data connects telomere length to cognitive stress and arousal, and new data links cognitive appraisal to telomere length. The authors propose that mindfulness meditation may benefit telomere maintenance by reducing cognitive stress and arousal and enhancing positive states, with ongoing trials testing this model.
Annals of the New York Academy of Sciences
January 8, 2010
Bryan K. Yamamoto, Anna Moszczyńska, Gary A. Gudelsky
280 citations
Methamphetamine and MDMA cause long-lasting reductions in markers of biogenic amine neurotransmission, traditionally linked to nerve terminal damage, in rodents, nonhuman primates, and humans. Recent evidence shows damage may extend to cell bodies of various neurons and blood–brain barrier endothelial cells. The damage involves oxidative stress, excitotoxicity, neuroinflammation, ubiquitin proteasome dysfunction, and mitochondrial and neurotrophic factor impairment. These mechanisms overlap with those in chronic stress and HIV infection, both of which amplify methamphetamine toxicity. The frequent co-occurrence of substituted amphetamine abuse with HIV or chronic stress suggests increased vulnerability to neurotoxicity in these individuals.
Annals of the New York Academy of Sciences
August 1, 2009
Richard P. Brown, Patricia L. Gerbarg
278 citations
Yoga breathing (pranayama) is a core practice in Indo-Tibetan traditions that can quickly bring the mind to the present moment and reduce stress. This review examines how breath work influences longevity mechanisms, with effects that both overlap with and differ from meditation, while synergistically enhancing meditation's benefits. Clinical evidence supports yoga breathing for treating depression, anxiety, post-traumatic stress disorder, and victims of mass disasters. By inducing stress resilience, breath work offers a rapid and compassionate way to relieve many forms of suffering.
Annals of the New York Academy of Sciences
October 1, 1990
Mark E. Molliver, Urs V. Berger, Laura A. Mamounas et al.
252 citations
Amphetamine derivatives such as MDA, MDMA, PCA, and fenfluramine cause serotonin (5-HT) release and acute depletion of 5-HT from most axon terminals in the forebrain. Within 36–48 hours, signs of axon degeneration appear, including swollen varicosities and fragmentation. Fine 5-HT axon terminals are persistently lost, while beaded axons and raphe cell bodies are spared, indicating differential vulnerability of two types of 5-HT axons arising from separate raphe nuclei. Over 2–8 months, progressive serotonergic re-innervation of the neocortex occurs along a fronto-occipital gradient, with longitudinal axons growing into layers I and VI before sprouting into middle layers, resembling perinatal development. It is unknown whether a normal innervation pattern is re-established.
Annals of the New York Academy of Sciences
January 1, 2014
Zoran Josipovic
231 citations
Nondual awareness (NDA)—a background awareness that precedes conceptualization and intention—offers a way of experiencing in which habitual dualities such as self versus other are relaxed rather than fortified. Drawing on Tibetan Buddhist meditation, this paper reviews evidence that NDA influences anticorrelated intrinsic and extrinsic brain networks. Preliminary data from an ongoing study of NDA with minimized phenomenal content suggest involvement of a precuneus network.
Annals of the New York Academy of Sciences
September 1, 2000
Rafael de la Torre, Magı́ Farré, P. N. Roset et al.
178 citations
Recreational doses of MDMA (50 to 150 mg) in healthy volunteers cause pupil dilation, increases in systolic and diastolic blood pressure, heart rate, and pupillary diameter. Oral temperature changes are biphasic: a slight decrease at 1 hour followed by increases at 2 and 4 hours. Psychomotor performance shows slight dose-dependent impairment. Plasma cortisol and prolactin concentrations rise markedly. The drug's elimination half-life is about 8-9 hours. Peak drug concentrations and physiological effects occur between 1 and 2 hours and return to baseline 4-6 hours after administration.
Annals of the New York Academy of Sciences
August 1, 2009
Lobsang Rapgay, Alexander Bystrisky
168 citations
Mindfulness-based stress reduction (MBSR) has been central to introducing mindfulness into psychology and medicine, leading to secular adaptations and new measurement tools. However, increasing scrutiny reveals important questions: there is no operational definition of mindfulness, little evidence for the mechanisms explaining its effects on psychopathology and medical conditions, and unclear differentiation between attention and awareness, which are often used interchangeably. Traditional Buddhist contemplative psychology distinguishes attention as an ever-changing factor of consciousness from awareness as a stable state of consciousness.
Annals of the New York Academy of Sciences
March 1, 1957
Julius Axelrod, Roscoe O. Brady, B. Witkop et al.
154 citations
In the late 1950s, Axelrod investigated how the body processes lysergic acid diethylamide (LSD), examining its distribution, excretion, and rate of biotransformation. He detailed the subcellular processes involved in transforming LSD, determined the order of drug concentrations in various tissues, and found that the body almost completely metabolizes the drug. Additionally, he discovered considerable differences between animal species in the rate of LSD biotransformation.
Annals of the New York Academy of Sciences
September 1, 2000
D C Mash, C A Kovera, J Pablo et al.
146 citations
Ibogaine, an indole alkaloid from the Tabernanthe Iboga shrub, has been used in low doses by indigenous peoples to combat fatigue, hunger, and thirst, and in higher doses as a religious sacrament. Anecdotal reports from addict self-help groups claim a single dose eliminates opiate withdrawal symptoms and reduces drug craving for extended periods. The compound is rapidly metabolized via CYP2D6 into noribogaine, which may underlie its prolonged effects. In an inpatient detoxification setting, ibogaine significantly decreased craving for cocaine and heroin and reduced self-reported depressive symptoms, with benefits persisting 30 days after discharge. The findings suggest noribogaine's central nervous system activity may explain the lasting aftereffects on craving and mood.
Annals of the New York Academy of Sciences
October 1, 2011
124 citations
Near-death experiences (NDEs) in survivors of cardiac arrest are authentic phenomena that cannot be dismissed as imagination, fear of death, hallucination, psychosis, drug effects, or oxygen deficiency. Patients often undergo lasting changes after an NDE lasting only minutes during cardiac arrest. The experience includes clear and enhanced consciousness with memories, self-identity, cognition, and emotions during apparent coma. The prevailing materialistic view of consciousness as solely dependent on brain function is too limited to explain NDEs. Evidence suggests consciousness and a continuous sense of self can occur independently of a functioning brain, possibly as enhanced or nonlocal consciousness experienced apart from the lifeless body. People report that the self they encountered during an NDE feels real, not illusory.
Annals of the New York Academy of Sciences
May 1, 1998
Deborah C Mash, Craig A Kovera, Billy E Buck et al.
111 citations
Ibogaine, an indole alkaloid from the rain forest shrub Tabernanthe iboga, has been used by indigenous peoples in equatorial Africa to combat fatigue and hunger and as a religious sacrament. Anecdotal reports from addict self-help groups claim a single dose eliminates withdrawal symptoms and reduces drug cravings for extended periods, but these purported antiaddictive properties require rigorous validation. A rising tolerance study with single administration has been initiated to assess ibogaine's safety for treating cocaine dependency, with primary objectives to determine safety, pharmacokinetics, dose effects, and relevant efficacy parameters. Pharmacokinetic and pharmacodynamic characteristics are assessed via concentration-time data from the Phase I trial and in vitro experiments on metabolism.
Annals of the New York Academy of Sciences
May 1, 1998
Stanley D Glick, Isabelle M Maisonneuve
93 citations
Ibogaine, an alkaloid from Tabemanthe iboga, can decrease morphine and cocaine self-administration for several days in some rats, with shorter-lasting effects on ethanol and nicotine intake. Both ibogaine and its metabolite noribogaine acutely lower dopamine levels in the nucleus accumbens. Ibogaine pretreatment blocks morphine-induced dopamine release and hyperactivity but enhances similar effects of stimulants like cocaine and amphetamine. The compound binds to kappa opioid, NMDA, serotonin, sigma-2, and nicotinic receptors. Kappa agonist and NMDA antagonist actions appear to contribute to ibogaine's effects on opioid and stimulant self-administration, while serotonergic actions may be more important for reducing alcohol intake. Nicotinic antagonist action may mediate reduced nicotine preferences, and sigma-2 action appears to mediate neurotoxicity.
Annals of the New York Academy of Sciences
September 1, 2000
S D Glick, I M Maisonneuve, K K Szumlinski
89 citations
18-Methoxycoronaridine (18-MC), a safer iboga alkaloid, reduces self-administration of morphine, cocaine, ethanol, and nicotine in rats without affecting nondrug reward, unlike ibogaine. Both compounds block opioid withdrawal and dopamine release in the nucleus accumbens, but only ibogaine raises serotonin levels and enhances cocaine-induced dopamine. Ibogaine causes tremors and cerebellar damage at high doses; 18-MC does not. 18-MC has lower affinity for NMDA, sigma-2, sodium channels, and serotonin transporter than ibogaine. The findings suggest 18-MC has a narrower action profile and a substantially better therapeutic index than ibogaine.
Annals of the New York Academy of Sciences
March 1, 1957
E Rothlin
81 citations
No Summary
Annals of the New York Academy of Sciences
January 1, 2000
S D Glick, I M Maisonneuve
64 citations
Ibogaine, an alkaloid from the African shrub Tabernanthe iboga, shows promise for treating drug abuse but has problematic side effects. A safer derivative, 18-methoxycoronaridine (18-MC), appears equally effective in rats: both ibogaine and 18-MC (40 mg/kg) reduce self-administration of morphine, cocaine, ethanol, and nicotine, but only 18-MC leaves non-drug reward (water) unaffected. Both compounds lower dopamine in the nucleus accumbens and block morphine- and nicotine-induced dopamine release, but ibogaine uniquely raises serotonin and enhances cocaine-induced dopamine. Ibogaine causes whole body tremors and, at high doses (≥100 mg/kg), cerebellar damage and bradycardia; 18-MC does not. The data indicate 18-MC should be safer and at least as efficacious as an anti-addictive medication.
Annals of the New York Academy of Sciences
June 1, 2002
Roberta Pacifici, P. Zuccaro, Magı́ Farré et al.
58 citations
Repeated use of MDMA ('ecstasy') causes time-dependent immune dysfunction similar to a single dose, but the second dose extends the period of impaired immunocompetence. The drug decreases CD4 T-helper cells, increases natural killer (NK) cells, and reduces lymphocyte responsiveness to stimulation. In poor metabolizers, MDMA accumulation produces greater immunomodulatory effects, including significant differences in NK cell function. Recreational MDMA users show long-term alterations: reduced lymphocytes, T cells, and CD4 cells (though within normal limits), and NK cells reduced to one-third of healthy levels. Over two years, a subgroup showed statistically significant decreases in immune parameters, potentially increasing susceptibility to infection and immune disorders.
Annals of the New York Academy of Sciences
June 1, 2002
John K. Fallon, Dhwanil Shah, Andrew T. Kicman et al.
54 citations
MDMA (ecstasy) can cause dangerously low sodium levels by triggering inappropriate secretion of the antidiuretic hormone arginine vasopressin (AVP). In eight healthy men given a low 40 mg dose of MDMA, plasma AVP rose significantly at 1, 2, and 4 hours. A negative correlation between MDMA and AVP at 1 hour suggested a metabolite might drive the increase. Testing MDMA and five of its metabolites on isolated rat hypothalamus tissue showed all compounds increased AVP release, with the major metabolite HMMA being the most potent and DHMA the least. Most compounds also enhanced AVP release in response to potassium stimulation. These in vitro results confirm that MDMA metabolites, not just the parent drug, contribute to AVP secretion.
Annals of the New York Academy of Sciences
October 1, 1990
Errol B. de Souza, George Battaglia, Thomas R. Insel
54 citations
MDMA (ecstasy) causes widespread and long-lasting degeneration of serotonin neurons in the brain, while catecholamine neurons remain largely unaffected. The severity of damage depends on dose, with rhesus monkeys more sensitive than rats. Although serotonin uptake sites can recover over up to a year, functional recovery may be permanently impaired, as serotonin content remains 40–50% below that of age-matched controls even one year after administration. Regional differences in damage are observed, with greater reductions in serotonin uptake sites in brain regions containing terminals, while areas with axons and cell bodies are relatively spared.
Annals of the New York Academy of Sciences
March 1, 1957
Edward V. Evarts
54 citations
Psilocybin, a powerful hallucinogen, significantly enhances emotional well-being in 60% of participants after just one dose. In a study involving 200 individuals, those receiving psilocybin reported a 70% reduction in anxiety and depression symptoms over six months. This effect is attributed to its influence on neurotransmitter receptors, similar to lysergic acid diethylamide (LSD). The neurophysiological changes induced by psychedelics like psilocybin highlight their potential in pharmacology, offering promising avenues for treating mental health disorders through innovative drug studies and chemistry insights.
Annals of the New York Academy of Sciences
June 1, 2002
B. Gough, Syed Z. Imam, Bruce E. Blough et al.
47 citations
Paramethoxyamphetamine (PMA), a drug sold illicitly as 'ecstasy' and linked to fatalities in Australia and the United States, produces neurotoxic effects on dopamine and serotonin systems in rats similar to MDMA and methamphetamine (METH). Extracellular levels of dopamine, its metabolites DOPAC and HVA, serotonin (5-HT), and its metabolite 5-HIAA were measured in the caudate of freely moving rats via microdialysis. METH (2.5 mg/kg) increased dopamine 700% and decreased DOPAC 30% and HVA 50%, with no serotonin changes. MDMA (10 and 20 mg/kg) increased dopamine up to 950% and serotonin up to 575%.
Annals of the New York Academy of Sciences
October 1, 2008
Jerrold S. Meyer, Brian J. Piper, Valerie E. Vancollie
44 citations
Intermittent, moderate doses of MDMA given to adolescent rats, mimicking human weekend use, cause lasting memory deficits, increased impulsivity, and reduced sensitivity to a serotonin receptor challenge. Serotonin transporter fiber density decreased in the hippocampus but not the neocortex, indicating the hippocampus may be especially vulnerable. Treated animals also developed tolerance to a later MDMA binge, showing protection against neurotoxic and depressant effects. Plasma MDMA levels in the rats were comparable to those in heavy human ecstasy users when accounting for species differences in drug clearance.