The Neural Basis of the Complex Mental Task of Meditation

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Medical Hypotheses (2003) 61(2), 282-291 2003 Elsevier Science Ltd. All rights reserved.

doi:10.1016/S0306-9877(03)00175-0

The neural basis of the complexmental task of meditation:neurotransmitter and neurochemicalconsiderationsA. B. Newberg,1 J. lversen"1University of Pennsylvania, Philadelphia, PA, USA; 2Stanford University, Stanford, CA 94309, USA

Summary Meditation is a complex mental process involving changes in cognition, sensory perception, affect,hormones, and autonomic activity. Meditation has also become widely used in psychological and medicalpractices for stress management as well as a variety of physical and mental disorders, However, until now, therehas been limited understanding of the overall biological mechanism of these practices in terms of the effectsin both the brain and body, We have previously described a rudimentary neuropsychological model to explain thebrain mechanisms underlying meditative experiences. This paper provides a substantial development byintegrating neurotransmitter systems and the results of recent brain imaging advances into the model. Thefollowing is a review and synthesis of the current literature regarding the various neurophysiological mechanismsand neurochemical substrates that underlie the complex processes of meditation. It is hoped that this modelwill provide hypotheses for future biological and clinical studies of rneditatlon, 2003 Elsevier Science Ltd, All rights reserved,

INTRODUCTIONThe complex mental task of meditation is potentially oneof the most important areas of research that may bepursued by science in the next decade. Meditation offersa fascinating window into human consciousness, psy-chology, and experience; the relationship betweenmental states and body physiology; emotional and cog-nitive processing; and the biological correlates of reli-gious experience. In the past thirty years, scientists haveexplored the biological effects and mechanisms of med-itation in great detail. Initial studies measured changes inautonomic activity such as heart rate and blood pressure,as well as electroencephalographic (EEG) changes. More

Received 1 November 2002Accepted 26 March 2003Correspondence to: Andrew B_ Newberg MD, Div is ion of Nuclear Medicine,110 Donner Bui lding, H.U.P., 3400 Spruce Street, Phi lade lphia, PA 19104,USA. Phone: +215-662-3092; Fax: +215-349-5843;E-mail: [email protected]

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recent studies have explored changes in hormonal andimmunological function associated with meditation.Studies have also explored the clinical effects of medita-tion in both physical and psychological disorders.Functional neuroimaging has opened a new window

into the investigation of meditative states by exploringthe neurological correlates of these experiences, Fivestudies, currently available in the literature (see Table 1),measured cerebral function during meditation tech-niques. These neuroimaging techniques include positronemission tomography [PET; (1-3)], single photon emis-sion computed tomography [SPECT; (4)], and functionalmagnetic resonance imaging [fMRI; (5)]. Each of thesetechniques provides different advantages and disadvan-tages in the study of meditation, Although functional MRIhas the ability of immediate anatomic correlation and hasimproved resolution over SPECT, itwould be very difficultto utilize for the study of meditation because ofthe noisefrom the machine and the problem of requiring the sub-ject to lie prone in the machine, an atypical posture formany forms of meditation. In fact, we attempted the use of
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The neural basis of the complex mental task of meditation 283

Table 1 Summary of current neuroimaging studies of medi tat ionStudy Type of Imaging Na Measuresmeditation modalityHerzog et al. (1) Yoga PET 8 CBF

Lou et al. (2) Tantric Yoga PET 9 CBF

Newberg et at , Tibetan SPECT 8 CBF(4)

Lazar et al. (5) Kundalini MRI 5 CBF

Kjaer et al. (3) Yoga Nidra PET 5

Results Critique

TFrontal lobe, Iparietallobe Meditation in the scanner,limited regional analysis,one t ime pointSubjects listened to tapeguiding the meditation,different forms of meditation,one t ime pointNo cross correlat ion withother modalit ies, SPECToffers lowest resolution,one t ime pointAttempted to factor in MRInoise to prevent distraction,smallest N, limited abilityto detect decreased CBF,multiple time pointsSubjects listened to tapeguiding the meditation,one t ime point , f irstneurotransmitter study

TParietal during focus onsel f, [hlppocarnpus, lPFCTPFC, thalamus, brain-stem,lPSPL

TPFC, parietal, hippocam-pus, temporal lobe cingu-late gyrus, hypothalamus

Dopamine [Dopamine in the striatum

a N= number of subjects.

fMRIwith one of our initial meditation subjects in orderto determine feasibility, but the subject found it extremelydifficult to carry out the meditation practice. WhilePETimaging also provides better resolution than SPECT,if one strives to make the environment relativelydistraction free to maximize the chances of having astrong meditative experience, then it is sometimes bene-ficial to perform these studies during non-clinical times,which may make PET radiopharmaceuticals such asfluorodeoxyglucose difficult to obtain. Finally, the func-tional imaging techniques of PET and SPECT offerthe opportunity to study changes in a variety of neuro-transmitter systems in the brain associated with medita-tion practices. Overall, functional brain imagingoffers important techniques for studying meditation, al-though the best approach may depend on factors relatedto each technique as well as specific parameters to bemeasured.

Inthis paper, we review existing data on the neuro-physiology and physiology of meditation practices, andwe attempt to integrate this data into a comprehensiveneurochemical model of such practices. However, thereare many possible neurochemical changes that may oc-cur during meditation, even though they may not occurinevery type of practice or in each individual. This modelis designed to provide a framework of the neurologicaland physiological correlates of meditative experiences,and to create a springboard for future research.

TYPES OF MEDITATIONAlthough there are many specific approaches to medita-tion, we have typically divided such practices into two

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basic categories. The first category is one in which thesubjects simply attempt to clear all thought from theirsphere of attention. This form of meditation is one inwhich the practitioner attempts to reach a subjective statecharacterized by a sense of no space, no time, and nothought. Further, this state is cognitively experienced asfully integrated and unified, such that there is no sense ofa self and other. This includes practices such as thoseassociated with traditions such as Theravada Buddhism(6). The second category is one in which the subjectsfocus their attention on aparticular object, image, phrase,or word, and it includes practices such as transcendentalmeditation and various forms of Tibetan Buddhism. Thisform of meditation is designed to lead one to a subjectiveexperience ofabsorption with the object of focus. There isanother distinction in which some meditation is guidedby following along with a leader, either in person or ontape, who is verbally directing the practitioner. Otherspractice the meditation on their own volition. We mightexpect that this difference between volitional and guidedmeditation should also be reflected in specific differencesin cerebral activation.Phenomenological analysis suggests that the end re-

sults of many practices of meditation are Similar, al-though these results might be described using differentcharacteristics depending on the culture and individual.Therefore, it seems reasonable that while the initialneurophysiological activation occurring during any gi-ven practice may differ, there should eventually be aconvergence. We present a description of volitionalmeditation, which will hopefully provide an overallframework from which any given type of meditation canbe considered (see Fig. 1).

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284 Newberg and Iversen

Arcuat e Nucl eus o f .- ,. LeftPFC RightPFC Anterior Glutamatethe Hypothalamus Cingulate+BE -f-- +glutamate - +Glutamate

+ BE via Arcuate Nne. ._ ~ - NAALADase ._~ -NAALADase ~ +NAAG+NAAG Nucleus accumbens ~

Left Thalamic Reticular .- ,------ Right ThalamicNucleus Reticular Nucleus .-+GABA +GABA f ~ Lateral Geniculate I----- Lat . Poster,ior Nuel.

!;-r LeftPSPL RightPSPL --- I Striatum I. , Glutamate Glutamate . .1 Nueleus Basalis 1 h GABA' T .1 +Acetylcholine 1 - Left Hippocampus ~I Right Hippocampus + Dopamine Glutamate Glutamate I Sub~tantia I

~NIgra

Left Amygdala Rigbt Amygdala - GABA~l Glutamate /1 l Glutamate I VentralThalamusLateral < I VentromedialHypothalamus Break through Hypothalamus. . , D. Raphe 1 Pineal 1arasympathetic Supraoptic NucleusI f-.ST +MT , +AVP,

+DMT .yParagigantocellular

NucleusSympathetic ,,.y+ increase Locus Ceruleus Paraventricular- decrease --_. --I Nucleus____. stimulate -NE---. inhibit - Cortisol

I

Fig. 1 Schemat ic overview of the neurophysiological network possibly associated with meditative states. The circuits and act ivationsgenerally apply to both hemispheres even though they may be ascribed to only one hemisphere on the diagram below.

ACTIVATION OF THE PREFRONTAL ANDCINGULATE CORTEXBrain imaging studies suggest that willful acts and tasksthat require sustained attention are initiated via activityin the prefrontal cortex (PFC), particularly in the righthemisphere (7-10). The cingulate gyrus appears to beinvolved in focusing attention, probably in conjunctionwith the PFC (11). Since meditation requires intense fo-cus of attention, it seems appropriate that a model formeditation begin with activation of the PFC, particularlyin the right hemisphere, as well as the cingulate gyrus.This notion is supported by the increased activity ob-served in these regions on several of the brain imagingstudies of volitional types of meditation, including thosefrom our laboratory (1,4,5). Inour study of eight TibetanBuddhist meditators, subjects had an intravenous line


placed in the arm, and were injected with a cerebralblood flow tracer while at rest in order to acquire a'baseline' image. They then meditated for approximately1h when they were again injected with the tracer whilethey continued to meditate. At the time of injection, thetracer was fixed in the brain so that when the imageswere acquired approximately 20 min later, they reflectedthe cerebral blood flow during the meditation state.Quantitative analysis demonstrated increased activity inthe PFC bilaterally (greater on the right) and the cingu-late gyrus during meditation. Therefore, meditation ap-pears to begin by activating the prefrontal and cingulatecortex associated with the will or intent to clear one'smind of thoughts or to focus on an object. One PETstudy of a guided type of meditation did not demon-strate increased prefrontal activity. However, a recent

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study showed decreased frontal activity during exter-nally guided word generation compared to internal orvolitional word generation (12). Thus, prefrontal andcingulate activation may be associated with the voli-tional aspects of meditation.

THALAMIC ACTIVATIONSeveral animal studies have shown that the PFC, whenactivated, innervates the reticular nucleus of the thala-mus (13), particularly as part of a more global attentionalnetwork (14). Such activation may be accomplished bythe PFC's production and distribution of the excitatoryneurotransmitter glutamate, which the PFC neurons useto communicate among themselves and to innervateother brain structures (15). The thalamus itself governsthe flow of sensory information to cortical processingareas via its interactions with the lateral geniculate andlateral posterior nuclei and also likely uses the glutamatesystem in order to activate neurons in other structures(16). The lateral geniculate nucleus receives raw visualdata from the optic tract and routes it to the striatecortex for processing (17). The lateral posterior nucleusof the thalamus provides the posterior superior parietallobule (PSPL)with the sensory information it needs todetermine the body's spatial orientation (18).When excited, the reticular nucleus secretes the in-

hibitory neurotransmitter y-arninobutyric acid (GABA)onto the lateral posterior and geniculate nuclei, cuttingoff input to the PSPLand visual centers in proportion tothe reticular activation (19). During meditation, due tothe increased activity in the PFC, particularly in the righthemisphere, there should be a concomitant increase inthe activity in the reticular nucleus of the thalamus.While brain imaging studies of meditation have not yethad the resolution to distinguish the reticular nuclei, ourrecent SPECT study did demonstrate a general increasein thalamic activity that was proportional to the activitylevels in the PFC. This finding is consistent with, butdoes not confirm, the specific interaction between thePFC and the reticular nuclei. If the activation of the rightPFC causes activity to increase in the reticular nucleusduring meditation, the result may be a decrease in sen-

sory input entering into the PSPL. Several studies havedemonstrated an increase in serum GABAduring medi-tation (see Table 2 for an overview of neurochemicalchanges during meditation), possibly reflecting in-creased central GABAactivity (20). This functional de-afferentation related to increased GABA would meanthat fewer distracting outside stimuli would arrive at thevisual cortex and PSPLenhancing the sense of focus.

Itshould also be noted that the dopaminergic system,via the basal ganglia, is believed to participate in regu-lating the glutamatergic system and the interactionsbetween the prefrontal cortex and subcortical structures.A recent PET study utilizing 11C-Raclopride to measurethe dopaminergic tone during Yoga Nidra meditationdemonstrated a significant increase in dopamine levelsduring the meditation practice (3). The experimentershypothesized that this increase may be associated withthe gating of cortical-subcortical interactions, leading toan overall decrease in readiness for action that is asso-ciated with this particular type of meditation. Futurestudies will be necessary to elaborate on the role of do-pamine during meditative practices, as well as on theinteractions between dopamine and other neurotrans-mitter systems.

PSPL DEAFFERENTATIONThe PSPL is heavily involved in the analysis and inte-gration of higher-order visual, auditory, and somaes-thetic information (21). It is also involved in a complexattentional network that includes the PFC and thalamus(22). Through the reception of auditory and visual inputfrom the thalamus, the PSPLis able to help generate athree-dimensional image of the body in space, provide asense of spatial coordinates in which the body is ori-ented, help distinguish between objects, and exert in-fluences in regard to objects that may be directly graspedand manipulated (23,24). These functions of the PSPLmay be critical for distinguishing between the self andthe external world. Itshould be noted that a recent studyhas suggested that the superior temporal lobe may playamore important role than the parietal lobe in body spatialrepresentation, although this has not been confirmed by

Table 2 Neurochemically related changes in serum concentration observed during meditation techniques and the central nervous systemstructures typically involved in their productionNeurochemical Observed change CNS structureArginine vasopressinGABAMelatoninSerotoninCortisolNorepinephrine~-Endorphin

Increased (48)Increased (20)Increased (74)Increased (38)Decreased (38,43)Decreased (38,39)Rhythm changed; levels unaltered (52)

Supraoptic nucleusThalamus, other inhibitory structuresPineal glandDorsal rapheParaventricular nucleusLocus ceruleusArcuate nucleus

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other reports (25). However, the actual relationship be-tween the parietal and temporal lobes, in terms of spatialrepresentation, remains to be fully elucidated.Regardless, we propose that deafferentation of these

orienting areas of the brain is an important concept inthe physiology of meditation. If, for example, deaffer-entation of the PSPL via the reticular nucleus's GABA-ergic occurs, an individual may begin to lose his or herusual ability to spatially define the self and help to orientthe self. Such a notion is supported by clinical findings inpatients with parietal lobe damage who have difficultyorienting themselves. The effects ofmeditation are likelyto be more selective, and instead of destroying the senseof self, they alter the perception of the self. Deafferen-tation of the PSPLhas also been supported by two im-aging studies demonstrating decreased activity in thisregion during intense meditation (1,4). Further, ourSPECT study showed a significant correlation betweenincreasing activity in the thalamus and decreasing ac-tivity in the PSPL.HIPPOCAMPAL AND AMYGDALAR ACTIVATIONIn addition to the complex cortical-thalamic activity,meditation might also be expected to alter activity in thelimbic system, especially since stimulation of limbicstructures is associated with experiences similar to thosedescribed during meditation (26,27). The hippocampusacts to modulate and moderate cortical arousal and re-sponsiveness via rich and extensive interconnectionswith the prefrontal cortex, other neocortical areas, theamygdala, and the hypothalamus (28). Hippocampalstimulation has been shown to diminish cortical re-sponsiveness and arousal; however, if cortical arousal isinitially at a low level, then hippocampal stimulationtends to augment cortical activity (29).The ability of thehippocampus to stimulate or inhibit neuronal activity inother structures likely relies upon the glutamate andGABAsystems, respectively (16). The partial deafferen-tation of the right PSPLduring meditation may result instimulation of the right hippocampus because of theinverse modulation of the hippocampus in relation tocortical activity. If, in addition, there is simultaneousdirect stimulation of the right hippocampus via thethalamus (as part of the known attentional network) andmediated by glutamate, then a powerful recruitment ofstimulation of the right hippocampus occurs. Righthippocampal activity may ultimately enhance the stim-ulatory function of the PFC on the thalamus via thenucleus accumbens, which gates the neural input fromthe PFC to the thalamus via the neuromodulatory effectsof dopamine (30,31).The hippocampus greatly influences the amygdala,

such that they complement and interact in the genera-


tion of attention, emotion, and certain types of imagery(28). It seems as though much of the prefrontal modu-lation of emotion is via the hippocampus and its con-nections with the amygdala (32). Because of thisreciprocal interaction between the amygdala and hip-pocampus, the activation of the right hippocampuslikely stimulates the right lateral amygdala as well. Theresults of the fMRI study by Lazar et al. (5) support thisnotion of increased activity in the regions of the amyg-dala and hippocampus during meditation.

HYPOTHALAMIC AND AUTONOMIC NERVOUSSYSTEM CHANGESThe hypothalamus is extensively interconnected withthe limbic system. Stimulation of the right lateralamygdala has been shown to result in stimulation of theventromedial portion of the hypothalamus with a sub-sequent stimulation of the peripheral parasympatheticsystem (33). Increased parasympathetic activity shouldbe associated with the subjective sensation first of re-laxation and, eventually, of a more profound quiescence.Activation of the parasympathetic system would alsocause a reduction in heart rate and respiratory rate. Allofthese physiological responses have been observed dur-ing meditation (34).Typically, when an individual's breathing and heart

rate slow down, the paragigantocellular nucleus of themedulla ceases to innervate the locus ceruleus (LC) ofthe pons. The LC produces and distributes norepineph-rine (NE)(35).NE is a neuromodulator that increases thesusceptibility of brain regions to sensory input by am-plifying strong stimuli, while Simultaneously gating outweaker activations and cellular 'noise' that fallbelow theactivation threshold (36). Decreased stimulation of theLC results in a decrease in the level of NE (37). Thebreakdown products of catecholamines such as NE andepinephrine have generally been found to be reduced inthe urine and plasma during meditation (38,39). Al-though this may Simply reflect the systemic change inautonomic balance, the changes are not inconsistentwith a cerebral decrease in NE levels as well. During ameditative practice, the reduced firing of the paragig-antocellular nucleus probably cuts back its innervationof the locus ceruleus, which densely and specificallysupplies the PSPLand the lateral posterior nucleus withNE (35). Thus, a reduction in NE would decrease theimpact of sensory input on the PSPL, contributing to itsdeafferentation.The locus ceruleus would also deliver less NE to the

hypothalamic paraventricular nucleus. The paraventric-ular nucleus of the hypothalamus typically secretescorticotropin-releasing hormone (CRH) in response toinnervation by NE from the locus ceruleus (40). This

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CRH stimulates the anterior pituitary to release adreno-corticotropic hormone (ACTH) (41). ACTH, in tum,stimulates the adrenal cortex to produce cortisol, one ofthe body's stress hormones (42). Decreasing NE from thelocus ceruleus during meditation would likely decreasethe production of CRH by the paraventricular nucleus,which would ultimately decrease cortisol levels. Moststudies have found that urine and plasma cortisol levelsare decreased during meditation (38,43,44).The drop in blood pressure associated with para-

sympathetic activity during meditation practices wouldbe expected to relax the arterial baroreceptors leadingthe caudal ventral medulla to decrease its GABAergicinhibition of the supraoptic nucleus of the hypothala-mus. This lack of inhibition can provoke the supraopticnucleus to release the vasoconstrictor arginine vaso-pressin (AVP) thereby tightening the arteries and re-turning blood pressure to its normal level (45). AVP hasalso been shown to contribute to the general mainte-nance of positive affect (46), to decrease self-perceivedfatigue and arousal, and to significantly improve theconsolidation of new memories and learning (47). Infact, plasma AVP has been shown to increase dramati-cally during meditation (48). The sharp increase in AVPshould result in a decreased subjective feeling of fatigueand an increased sense of arousal. It could also help toenhance the meditator's memory of his experience,perhaps explaining the subjective phenomenon thatmeditative experiences are remembered and describedin very vivid terms.

PFC EFFECTS ON OTHER NEUROCHEMICALSYSTEMSAs a meditation practice continues, there should becontinued activity in the PFC associated with the indi-vidual's persistent will to focus attention. In general, asPFC activity increases, it produces ever-increasing levelsof free synaptic glutamate in the brain. Increased gluta-mate can stimulate the hypothalamic arcuate nucleus torelease ~-endorphin (49). ~-endorphin (BE)is an opioidproduced primarily by the arcuate nucleus of the medialhypothalamus and distributed to the brain's subcorticalareas (50). BE is known to depress respiration, reducefear, reduce pain, and produce sensations of joy andeuphoria (51). That such effects have been describedduring meditation may implicate some degree of BE re-lease related to the increased PFC activity. Meditationhas been found to disrupt diurnal rhythms of BE andACTH (52). However, it is likely that BE is not the solemediator in such experiences during meditation becausesimply taking morphine-related substances does notproduce equivalent experiences as in meditation andone very limited study demonstrated that blocking the


opiate receptors with naloxone did not affect the expe-rience or EEGassociated with meditation (53).Glutamate activates N-methyl-o-aspartate receptors

(NMDAr), but excess glutamate can kill these neuronsthrough excitotoxic processes (54). We propose that ifglutamate levels approach excitotoxic concentrationsduring intense states ofmeditation, the brain might limitits production of N-acetylated-et-linked-acidic dipepti-dase, the enzyme responsible for converting the en-dogenous NMDAr antagonist N-acetylaspartylglutamate(NAAG) into glutamate (55). The resultant increase inNAAG would protect cells from excitotoxic damage.There is an important side effect, however, since theNMDAr inhibitor, NAAG, is functionally analogous tothe disassociative hallucinogens ketamine, phencycli-dine, and nitrous oxide (56). These NMDAr antagonistsproduce a variety of states that may be characterized aseither schizophrenomimetic or mystical, such as out-of-body and near-death experiences (57).

AUTONOMICCORTICAL ACTIVITYIn the early 1970s, Gellhorn and Kiely developed amodel, based almost exclusively on autonomic nervoussystem (ANS) activity, of the physiological processesinvolved in meditation. Although the model was some-what limited, it indicated the importance of the ANSduring such experiences (58). These authors suggestedthat intense stimulation of either the sympathetic orparasympathetic system, if continued, could ultimatelyresult in simultaneous discharge of both systems (whatmight be considered a 'breakthrough' of the other sys-tem). Several studies have demonstrated predominantparasympathetic activity during meditation associatedwith decreased heart rate and blood pressure, decreasedrespiratory rate, and decreased oxygen metabolism(34,43,59). However, a recent study of two separatemeditative techniques suggested a mutual activation ofparasympathetic and sympathetic systems by demon-strating an increase in the variability of heart rate duringmeditation (60). The increased variation in heart ratewas hypothesized to reflect activation of both arms ofthe autonomic nervous system. This notion is consistentwith recent developments in the study of autonomicinteractions (61) and also fits the characteristic descrip-tion of meditative states in which there is a sense ofoverwhelming calmness as well as Significant alertness.It should be noted that based upon current data, it is

not clear if one hemisphere would exclusively initiatethe neurological sequence of events over the other. Thismodel presents the activity beginning in the righthemisphere, although other practices may activate theleft first and some may be bilateral. Furthermore, it maybe that the breakthrough of activity in the autonomic



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nervous system may help with the stimulation of brainstructures in both hemispheres. The other point aboutthe model as presented is that all of the changes couldoccur in both hemispheres even though some events areassociated with only one of the hemispheres in themodel presented.

OTHER NEUROTRANSMITTER ACTIVITYActivation of the autonomic nervous system can resultin intense stimulation of structures in the lateral hypo-thalamus and median forebrain bundle, which areknown to produce both ecstatic and blissful feelingswhen directly stimulated (62). Stimulation of the lateralhypothalamus can also result in changes in serotonergicactivity. In fact, several studies have shown that aftermeditation, the breakdown products of serotonin (5-HT)in urine are significantly increased, suggesting an overallelevation in (5-HT)during meditation (38).Serotonin is aneuromodulator that densely supplies the visual centersof the temporal lobe. Within the temporal lobe, itstrongly influences the flow of visual associations gen-erated by this area (35). The cells of the dorsal rapheproduce and distribute 5-HT when innervated by thelateral hypothalamus (63) and also when activated bythe prefrontal cortex (64). Moderately increased levels of5-HT appear to correlate with positive affect, while low5-HT often signifies depression (65). This relationshiphas clearly been demonstrated with regards to the effectsof the selective serotonin reuptake inhibitor medicationswhich are widely used for the treatment of depression.When cortical 5-HT2 receptors (especially in the tempo-ral lobes) are activated, however, the stimulation canresult in a hallucinogenic effect. Tryptamine psychedel-ics such as psylocybin and LSDseem to take advantageof this mechanism to produce their extraordinary visualexperiences (66). These visual hallucinations seem tooccur because 5-HT inhibits the lateral geniculate nu-cleus, greatly reducing the amount of visual informationthat can pass through (67,68). If combined with reticularnucleus inhibition of the lateral geniculate, 5-HT mayincrease the fluidity of temporal visual associations inthe absence of sensory input, possibly resulting in in-ternally generated imagery that has been describedduring certain meditative states.Increased 5-HT levels can affect several other neuro-

chemical systems. An increase in serotonin has an effecton dopamine suggesting a link between the serotonergicand dopaminergic systems that may enhance the feel-ings of euphoria (69) that are frequently described dur-ing meditative states. Serotonin, in conjunction with theincreased glutamate, has been shown to stimulate thenucleus basalis to release acetylcholine (ACh).ACh hasimportant modulatory influences throughout the cortex


(70,71). For example, increased acetylcholine in thefrontal lobes has been shown to augment the attentionalsystem, and in the parietal lobes it tends to enhanceorienting without altering sensory input (22). While nostudies have evaluated the role of acetylcholine inmeditation, it appears that this neurotransmitter mayenhance the attentional component as well as the ori-enting response in the face of progressive deafferenta-tion of sensory input into the parietal lobes duringmeditation. Increased serotonin, combined with lateralhypothalamic innervation of the pineal gland, may leadthe latter to increase production of the neurohormonemelatonin (MT) from the conversion of 5-HT (72). Mel-atonin has been shown to depress the central nervoussystem and reduce pain sensitivity (73). During medita-tion, blood plasma MT has been found to increasesharply (74), which may contribute to the feelings ofcalmness and decreased awareness of pain (75). Undercircumstances of heightened activation, pineal enzymescan also endogenously synthesize the powerful halluci-nogen 5-methoxy-dimethyltryptamine (DMT) (76). Sev-eral studies have linked DMT to a variety of mysticalstates, including out-of-body experiences, distortion oftime and space, and interaction with supernatural enti-ties (77,78). Hyperstimulation of the pineal at this step,then, could also lead to DMT production that could beassociated with the wide variety of mystical-type expe-riences associated with that hallucinogen.

CONCLUSIONMore avenues still need to be explored to better eluci-date the intricate mechanisms underlying meditativepractices. Most currently available studies of the bio-logical correlates ofmeditation suffer from a low numberof subjects, lack of control conditions, and difficulty infactoring out confounding variables. Furthermore,knowledge of neurotransmitter systems is highly com-plex and continually being refined. Thus, it may be verydifficult to assess if all of the brain structures and neu-rotransmitter systems function in an integrated mannersuch as suggested in this paper. However, the neuro-physiological effects that have been observed duringmeditative states seem to outline a consistent pattern ofchanges involving certain key cerebral structures inconjunction with autonomic and hormonal changes.These changes are also reflected in neurochemicalchanges involving the endogenous opioid, GABA,nor-epinephrine, and serotonergic receptor systems. Themodel presented here, based on current literature aboutthe interaction of these systems, as well as brain imagingstudies of meditative techniques, is an integrated hy-pothesis that may help to elucidate the mechanism un-derlying the physical and psychological effects of such

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The Neural Basis of the Complex Mental Task of Meditation

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