(a) Total volume of the brain by morphometry comparing patients and normal controls of the same age and sex. (b) Volume measurements in parietal lobe comparing patients and normal controls of the same age and sex
One of the pioneering works in this field  found that meditators with an average of 7–9 years of experience meditating 40 min a day showed increased cortical thickness in the insula, in somatosensory cortex, frontal areas, and visual and auditory cortex in comparison with subjects without meditation experience. In addition, the cortex in the frontal areas (areas 9 and 10) of the meditators who were between 40 and 50 years old had the same thickness as that of control subjects of 20–30 years of age, which would indicate that meditation may promote the preservation of cortical areas associated with meditative activity.
Another research group  conducted a study in which the thickness of the cerebral cortex was assessed as high or low sensitivity to pain and by whether the subject practiced meditation or not. Those results showed greater thickness of the anterior cingulate cortex and secondary somatosensory areas in meditators. That study demonstrated that the practice of meditation is linked to increases in the thickness of those areas. Because the face is also linked to pain sensitivity and emotions, the practice of meditation may also be useful in the treatment of diseases such as chronic pain. In this same line, it was observed that a relatively brief intervention, 8 weeks of meditation practice for an average of 27 min a day, was sufficient to induce changes in left parietal structures such as the hippocampus, posterior cingulate, temporoparietal junction, and cerebellum .
These types of studies provide empirical evidence that the insula is implicated not only functionally but also structurally in the management of emotions . In subjects performing a task related to interoceptive perception, the density of grey matter in this area correlated positively with the effectiveness at the task. Studies on meditators found similar results. If the subjects are trained in these tasks, they show greater efficiency at the tasks and higher density of the insula. In this field, one study that was conducted on long-term meditators  measured the density of grey matter in areas previously involved in meditation showed increases in grey matter in areas of the right anterior insula, confirming previous results  in which the same structure showed a greater thickness in meditators.
Despite the diversity of findings, it appears that the anterior cingulate cortex and other areas such as the medial prefrontal cortex or secondary somatosensory areas are changed by long-term meditation practice and even, as shown in some current studies , in beginners. These studies may shed light on future treatments for diseases involving attentional deficits .
The notion that a largely mental practice, such as meditation, can produce such changes is further supported by studies showing structural differences after short-term mental training for working memory  and reasoning abilities . Nevertheless, we reiterate that evidence for meditation as the causative factor in structural changes in the brain remains limited. Ultimately, brain morphology differences are important only inasmuch as they relate to altered behavior and subjective well-being. Establishing such relationships should therefore be a paramount concern in future research.
Microstructural changes in white matter can be revealed by specialized MRI brain imaging techniques such as DTI. This method analyzes proton diffusion in tissue, which is more restricted in white matter than in grey matter. Fractional anisotropy supplements increased myelination, diameter, and axon compaction (See Fig. 27.2). Although the adult brain was once seen as a rather static organ, it is now clear that the organization of brain circuitry is constantly changing as a function of experience or learning .
Difusion tensor imaging (DTI) and fiber tractography of the corpus callosum
Several groups have recently shown pronounced structural connectivity throughout the entire brain within major projection pathways, commissural pathways, and association pathways in meditators compared with controls. The largest group differences were observed within the corticospinal tract, the temporal component of the superior longitudinal fasciculus, and the uncinate fasciculus.
A previous study showed that 4 weeks of integrative body–mind training (IBMT) (11 h in total) enhanced fractional anisotropy in several brain areas involved in communication to and from the anterior cingulate cortex, including the corpus callosum and the anterior and superior corona radiata . As with previous studies using fMRI, we must consider these data with caution because the finding that so little training can result in such profound structural changes has generated substantial controversy.
Another recent study of meditators compared with controls showed significantly greater cortical thickness in the anterior regions of the brain in both frontal and temporal areas, including the medial prefrontal cortex, superior frontal cortex, the temporal pole, and the middle and interior temporal cortices. Significantly thinner cortices were found in the posterior regions of the brain located in the parietal and occipital areas, including the postcentral cortex, inferior parietal cortex, middle occipital cortex, and posterior cingulate cortex. Furthermore, in the region adjacent to the medial prefrontal cortex, both higher fractional anisotropy values and greater cortical thickness were observed. These signs suggest that long-term meditators have structural differences in both grey and white matter .
In a recent study conducted by our research group , meditators showed a significantly lower mean diffusivity (i.e., apparent diffusion coefficient [ADC]) in the left parietal white matter than did the controls, and the mean diffusivity was correlated with time spent meditating (See Fig. 27.3). Our results show the time-course of white matter neuroplasticity in long-term meditation. The increased myelination would enhance communication among cortical areas resulting in enhanced performance. Our study also showed a negative correlation between the lower ADC in the left posterior parietal white matter and years of meditation. Thus, the improved self-regulation following IBMT might be mediated via the increased communication efficiency between the left posterior parietal lobe and other brain areas. These results imply that the enhanced integrity of white matter fibers through long-term meditation might reflect increased numbers of brain fibers or increased axonal caliber. Increased myelination may occur as a consequence of increased neural firing in active brain areas during training .
Difusion tensor imaging (DTI) and fiber tractography. Area where this increased axonal connectivity in meditators compared with nonmeditators controls (circle and star)
In our study , the primary somatosensory cortex, part of the postcentral gyrus which receives the bulk of thalamocortical projections from the sensory input fields, showed no significant decrease in fractional anisotropy in meditators compared with age-matched nonmeditators. The results only confirmed a nonsignificant trend of reduced anisotropy in the postcentral gyrus. Asymmetry of anisotropy has been reported in the superior longitudinal fasciculus , showing asymmetry with the left greater than the right. Another study found that mindfulness meditators more robustly activated the left anterior, posterior, and mid-insula and the thalamus .
Findings converge on several brain regions hypothesized to be involved in meditation based on results from functional neuroimaging, behavioral and clinical research, and phenomenological reports of meditative experience. These include regions key to meta-awareness and introspection (rostrolateral prefrontal cortex/area 10), exteroceptive and interoceptive body awareness (sensory cortices and insular cortex, respectively), memory consolidation and reconsolidation (hippocampus), regulation of the self and emotions (anterior and mid-cingulate, and orbitofrontal cortex, respectively), and finally intra- and interhemispheric communication (superior longitudinal fasciculus and corpus callosum, respectively).
To our knowledge, there is only one spectroscopic study on meditators which was performed by our research group , in which mI was increased in the posterior cingulate gyrus and glutamate, NAA and ratio of NAA/Cr were reduced in the left thalamus in meditators. We found a significant positive correlation between years of meditation and mI levels in the posterior cingulate. We also found significant negative correlations between years of meditation and levels of glutamate, NAA, and NAA/Cr in the left thalamus.
The current finding of increased mI in the posterior cingulate gyrus in long-term meditators seems counterintuitive. Changes in mI concentrations might reflect disturbances in fluid homeostasis and cellular signalling.
The precise mechanism of action on the central nervous system is not yet known, but the evidence presented here implicates the activation of microglia following the peripheral injection of interleukin-2. In addition, there is evidence that interleukin-2-induced neurochemical changes might have a delayed functional relevance for affective conditions such as anxiety-like behavior. Consistent with this assumption, cytokines modulate serotonergic neurotransmission and enhance the catabolism of tryptophan (serotonin precursor), leading to a reduction in the levels of serotonin and an increase in tryptophan catabolites.
Glutamate activates several receptors, including N-methyl-d-aspartate receptors (NMDAr). A glutamate excess can kill neurons through excitotoxic processes. If glutamate levels approach excitotoxic concentrations during intense states of meditation, the brain may limit its production of N-acetylated-a-linked-acidic dipeptidase, the enzyme responsible for converting the endogenous NMDAr antagonist N-acetylaspartylglutamate into glutamate .
MRS may detect decreases in glutamate content (See Fig. 27.4). There may be a consequence of a change in metabolic activity reflecting decreased function or viability of neurons because Glutamate, similarly to NAA, is located primarily in neurons . The function of NAA within axons in the white matter is unknown, but it may contribute to the synthesis of neurotransmitters . The question remains as to whether the depletion of NAA levels could signify a decreased activation of inhibitory neuronal pathways in meditators. The depletion of the NAA concentration may reflect decreased mitochondrial metabolism, which might correlate with years of meditation.
Differences on glutamate (Glu) levels in left thalamus between meditators and healthy nonmeditators
Pathology and Mindfulness
Beyond the finding that brain areas are involved in the practice of meditation, studies are beginning to focus on determining whether it has practical utility in the treatment of various pathologies, with the purpose of generating new or better interventions. Although there are a number of studies in which mindfulness and meditation are used to treat conditions such as psychiatric relapse into depression, other forms of anxiety or addiction relapse prevention , there are few studies to date that also involve scanning of brain substrate, but we have tried to introduce the most relevant examples. One such study  sought to evaluate how practicing mindfulness can prevent depression. Thus, with the use of fMRI, 19 participants performed a breathing task, and others performed a stress-inducing task. Non-reactivity was inversely correlated with vulnerability to depression and also with activity in the insula. These results show that in stressful situations, the practice of mindfulness can be protective and allow better responses to negative emotional stimuli.
Reducing anxiety has been associated with the emotional evaluation of external stimuli, leading to expect that people who practice mindfulness, as mentioned earlier in this chapter, have the ability to reduce anxiety. There is a recently published study  in which participants were trained in mindfulness for 4 days, achieving a reduction of anxiety in each session in which participants meditated. These studies should be considered with caution because, as the authors comment, this reduction of anxiety can be a result of the relaxation produced by the distraction of the training from the causes of anxiety, and anxiety returned to initial levels after the training.
Another disorder addressed through meditation is bipolar disorder, in which patients have increased levels of anxiety and poor regulation of emotions. In the first fMRI study in patients with bipolar disorder , patients and healthy subjects were trained in the practice of mindfulness. Their results showed that patients had a reduction in the activity of the medial prefrontal cortex and improved outcomes for anxiety and emotion regulation.
We have discussed in this chapter how certain areas of the brain work differently in meditators compared with people who do not practice meditation. The most important areas addressed are the anterior cingulate cortex, related to care; the insula, associated with consciousness of body and various sections of the prefrontal cortex, which have been linked to the regulation of emotions. The field of neuroimaging is making great strides in understanding the utility of the practice of mindfulness, and the proof of this is the study of connectivity and resting. It is true that neuroscientific knowledge of this topic is still sparse, particularly relating to higher stages of meditation practice. However, the dialogue between research and contemplation is beginning to bear fruit. A major challenge for the future is to better understand how, and to what extent, meditation is associated with differences in brain morphology, and whether the magnitude of these differences indicates any practical significance. Meditation can change the brain and thereby make us different people.
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