Neurocase
The Neural Basis of Cognition

ISSN: 1355-4794 (Print) 1465-3656 (Online) Journal homepage: http://www.tandfonline.com/loi/nncs20

Hyperreligiosity in malignant brain tumors: a case
report and accompanying bibliographic review
Alberto Carmona-Bayonas, Paula Jiménez-Fonseca, Carlos Vázquez Olmos &
Juan Vega Villar
To cite this article: Alberto Carmona-Bayonas, Paula Jiménez-Fonseca, Carlos Vázquez Olmos
& Juan Vega Villar (2016): Hyperreligiosity in malignant brain tumors: a case report and
accompanying bibliographic review, Neurocase
To link to this article: http://dx.doi.org/10.1080/13554794.2016.1265985

Published online: 12 Dec 2016.

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Date: 14 December 2016, At: 03:49

NEUROCASE, 2016
http://dx.doi.org/10.1080/13554794.2016.1265985

REVIEW

Hyperreligiosity in malignant brain tumors: a case report and accompanying
bibliographic review
Alberto Carmona-Bayonasa, Paula Jiménez-Fonsecab, Carlos Vázquez Olmosc and Juan Vega Villard,e
a
Department of Hematology & Medical Oncology, Hospital Universitario Morales Meseguer, Murcia, Spain; bOncology Service, Hospital Universitario
Central de Asturias, Oviedo, Spain; cRadiology Service, Neuro-radiology Section, Hospital Universitario Morales Meseguer, Murcia, Spain; dRadiology
Service, Hospital Universitario de Getafe, Madrid, Spain; eDepartment of Neurology, Hospital Universitario Central de Asturias, Oviedo, Spain

ABSTRACT

ARTICLE HISTORY

Religion is a complex cognitive process with biopsychosocial and cultural dimensions, product of the
activation of different circuits of the neocortex. In some cases, religiosity can appear as a pathological
correlate in patients with brain lesions in the areas involved. We present the clinical case of a patient
with an astrocytoma in the right prefrontal region, with apparent inflammatory involvement of the right
temporal lobe. This tumor debuted almost exclusively as an alteration of personality consisting of
hyperreligiosity, logorrhea, and mystical experiences. A review of the literature has been conducted and
possible pathophysiological mechanisms are proposed.

Received 16 December 2015
Accepted 23 November
2016

Introduction
In his novel Lying Awake (Salzman, 2000), Mark Salzman
describes the case of a Carmelite nun who wrote an abundance of poetry and essays and who called herself Sister John
of the Cross, in remembrance of the XVI century Spanish
mystic poet. While writing her texts, she had exquisite visions
and mystical experiences. Her writings are an inspiration for
many people both inside and outside the congregation. One
day, those profound spiritual experiences were found to be
due to right temporal lobe (RTL) epilepsy, caused by a brain
tumor, thereby providing a rational explanation for her headache, her numinous visions, and for her passion for writing.
This constellation of symptoms consisting of hyperreligiosity,
mystical experiences, hypergraphia, and hyposexuality has
been reported in patients with RTL epilepsy and is known as
Gastaut–Geschwind syndrome (Trimble & Freeman, 2006). The
novel revolves around a person endowed with delicate poetic
sensitivity, who must confront the rational explanation for a
medical disorder more than mystical or supernatural causes
and, in so doing, must undergo surgical treatment that will
end up by removing the source of experiences that, for years,
have validated her religious vocation.
Fictional literature has managed to imaginatively recreate
physicians’ and patients’ hopes, doubts, fears, and inner conflicts
that are normally inaccessible for direct scrutiny, hereby enabling
us to reflect on existential aspects of neurological diseases or the
human condition. However, fiction inevitably entails prototypical
descriptions that often do not correspond to how these diseases
manifest in the real world. In medical literature (as opposed to
fiction), there is not an abundance of pure cases of hyperreligiosity associated with neurological diseases.
The following is the case report and overview of a patient
in care at our hospital for several months, who had assimilated
the product of a diseased state of mind into her self or her ego.
CONTACT Alberto Carmona-Bayonas

alberto.carmonabayonas@gmail.com

© 2016 Informa UK Limited, trading as Taylor & Francis Group

KEYWORDS

Hyperreligiosity; astrocytoma; limbic encephalitis;
hallucinations; ecstatic
seizures

In this case, there was also a medical procedure that could
alleviate her symptoms, albeit at the expense of eradicating
precious religious, intimate experiences that, in the short term,
provided her with tremendous emotional well-being.

Result
The patient was a 60-year-old female at the time of diagnosis
who was happy and positive by nature. In the previous two
months, her neurobehavior had changed, exhibiting apathy,
sadness, abulia, withdrawal, subtle changes in personality
noticed by her family, slowness, awkwardness, and exacerbation of her religious behavior. The people around her attributed these symptoms to a reactive depressive disorder due to
the cancer a relative had recently suffered and for whom she
was still caring at the time.
The patient had no history of neurological diseases, psychotic
disorders, anxiety, or mood disorders, except for a self-limiting
adjustment disorder years earlier that had resolved without requiring medication. Insofar as her personality traits were concerned,
she was not a woman given to exaltation, suggestion, or repeated
obsessions. These characteristics were in stark contrast to the fact
that in the space of a very short time, she had developed a
growing interest in the Bible and other sacred writings and
spent the hours of the day reciting endless religious litanies.
The patient had not displayed strong faith up until that
time, despite the fact that she lived in one of the communities
having the highest percentage of practicing Catholics in the
world. However, she did consider herself to be a believer;
hence, it was not a case of religious conversion as previously
reported in the literature (Waxman & Geschwind, 1974).
The religious logorrhea surprised the people around her,
although she perceived it to be valuable and positive, instilling
in her a sense of tremendous well-being. There was no sign of

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A. CARMONA-BAYONAS ET AL.

psychomotor agitation, nor could any fear, commotion, mania,
obsession, or worry be inferred from her behavior. The patient
usually recorded the audio of her mystical sessions in which she
stated that she was seeing, feeling, and conversing with the
Virgin Mary. The patient’s mystical experiences presented in the
form of visual, auditory, and other sensory hallucinations, all of
which were religious and had to do with the Virgin Mary. These
episodes could last for hours or even days, displaying no associated seizures, neurological deficits, loss of consciousness, or
amnesia of what had happened once the episode had passed.
Timewise, they did not appear to be episodic and followed no
preestablished time pattern. Her mind interpreted and reelaborated these episodes in line with her way of thinking. Days after
these experiences, she was less ecstatic, although she maintained her faith and continued to think that the experiences
had been both valid and real.
Our patient did not have the same cultural baggage that
Salzman attributes to the nun in his book. Even so, she changed
the essays for audio recordings that she felt compelled to make
with exceptional diligence. In these recordings, she spoke with
great emotion about how the Virgin Mary was everyone’s
“beloved mother” and, hence, was therefore her mother, too.
She also talked to her about how to soothe and save the world.
The patient underwent a brain magnetic resonance imaging (MRI) in an MRI LX 1.5T, GE Medical Systems, Milwaukee
(WI), equipment. The imaging protocol included T1-weighted
image (T1WI) and T2-weighted image (T2WI), fluid attenuation
inversion recovery sequence, univoxel proton magnetic resonance spectroscopy, diffusion-weighted imaging (DWI), and a
T1WI with intravenous contrast (gadolinium).
Conventional images showed a lesion located in the cortex
and subcortical white matter in the middle frontal gyrus (prefrontal region) and a deeper bulky mass centered in the genu
of the corpus callosum. These lesions had a heterogeneous
signal intensity on T2WI and fluid attenuation inversion recovery with internal areas of necrosis and hemorrhage and were
surrounded by white matter involvement compatible with

Figure 1. Axial T2WI shows the cortical and subcortical lesion in the right frontal
lobe and the bulky mass centered in the genu of the corpus callosum (arrows).

vasogenic edema, although microscopic infiltration interconnecting the lesions was probably present (Figure 1). On DWI
and apparent diffusion coefficient (ADC) maps, a restricted
diffusion in the periphery of the lesions could be seen,
which correlated with the pattern observed on T1WI after
intravenous gadolinium administration consisting of a predominant peripheral enhancement (Figure 2). The magnetic resonance spectroscopy centered within the lesion of the corpus
callosum identified increased choline and lipids and decreased
N-acetylaspartate.
MRI also showed thickening and homogeneously increased
signal intensity on T2WI in the right medial temporal lobe
(MTL) where DWI and ADC maps revealed slightly increased

Figure 2. (a): Axial T1WI with gadolinium shows peripheral heterogeneous enhancement of the lesions. (b): On ADC map a facilitated central diffusion and
restriction in the peripheral component of the tumors is seen (arrows).

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3

Figure 3. (a): Axial T2WI in which the involvement of the medial region of the RTL can be seen (arrow). (b): ADC map shows slightly increased signal intensity in
relation with facilitated diffusion (arrow).

diffusion and no enhancement on the study with intravenous
contrast (Figure 3). This right medial temporal involvement
behaved differently from the other lesions and was distinctly
separate from them, which led to the initial, imaging-based
suspicion that it could be a high-grade, multicentric glial
tumor with peritumoral edema.
Post-processing techniques were performed and mean diffusivity and fractional anisotropy maps were obtained. Overall,
an increased mean diffusivity in the involved areas and a
decreased fractional anisotropy were seen. In addition, colored
orientation fractional anisotropy maps were obtained making
it possible to assess the involved fasciculus that included
association fibers such as the superior longitudinal fasciculus
and the superior fronto-occipital fasciculus, projection fibers
such as the corona radiata, and commissural fibers such as the
commissure of the corpus callosum (Figure 4).
A right frontal biopsy was taken, and the tumor was seen to
correspond histologically to a glioblastoma multiforme. No
electroencephalographic evaluation was undertaken at that
time given the patient’s evolution and decline. The neoplasm
was beyond the limits of neurosurgery and was therefore
treated with radiotherapy and chemotherapy (temozolomide),
as per the standard protocol for this type of tumor (Stupp’s
schedule) (Stupp et al., 2009). Antipsychotic treatment (haloperidol 15 mg per day) was also prescribed, as these cases
sometimes respond to drugs of this type. No anticonvulsant
treatment was prescribed. The patient completed the radiochemotherapy protocol in October 2012. Over the course of
the five weeks that treatment lasted, the rapture and evangelical visions gradually disappeared, although she continued to
believe that they were valid and true. We did not see any
changes in behavior. Two months after completing radiotherapy, the patient suffered an ischemic stroke of the left middle
cerebral artery and was unable to continue her cancer treatment with temozolomide. At that time, the patient underwent
non-enhanced cerebral computed tomography (CT) that
showed full resolution of the changes in the right MTL

Figure 4. Colored orientation FA map where the right frontal and corpus
callosum tumors (TM), as well as the tracts of white matter of the superior
fronto-occipital fasciculus (SFOF), superior longitudinal fasciculus (SLF), corona
radiata (CR), and corpus callosum (CC) can be identified. To view this figure in
color, please see the online version of this journal.

(Figure 5 and section on “Discussion”). Eight months after
the diagnosis of her brain tumor, in April 2013, the patient
passed away due to tumor progression. During the months
following her stroke, she was highly impaired in general, with
severe cognitive dysfunction, and was cared for by a palliative
homecare unit.

Discussion
We must begin by pointing out that neurobehavioral disorders
can be the first symptom of intracranial lesions (Blustein &

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A. CARMONA-BAYONAS ET AL.

Figure 5. (a): Initial nonenhancement brain CT exhibits slight thickening and hypodensity of the right MTL (arrowheads). (b): Two months later, morphology and
density of the right MTL (arrowheads) are normal. Hyperdense middle cerebral artery sign associated with thrombosis (blue arrow). To view this figure in color,
please see the online version of this journal.

Seeman, 1972); any patient over the age of 40 years with
altered mental, emotional, or cognitive status should therefore
be evaluated by a physician and, if other causes (e.g., medications, substance abuse, etc.) are ruled out, neuroimaging
should be ordered. Primary psychiatric diseases tend to
debut earlier, in adolescence or young adulthood.
Briefly, this patient’s pathology is compatible with complex partial seizures originating in the right MTL, with religious phenomenology in spite of being unable to perform
an electroencephalogram due to the poor clinical course.
On imaging, the findings suggest a multifocal glioblastoma
with right frontal and corpus callosum involvement, adjacent vasogenic edema, as well as an area where the signal
is altered in the temporal lobe, probably related to postictal
changes, without ruling out other inflammatory (limbic
encephalitis) or tumor-related (gliomatosis cerebri) disturbances. In fact, the glioblastoma multiforme is a tumor
having generally diffuse margins, resulting from the invasion of adjacent tissues. Furthermore, it is typically surrounded by cerebral edema and multifocal in 10–20% of
the cases, although it is less frequently multicentric (Kyritsis,
Levin, Yung, & Leeds, 1993). As illustrated by this case, the
heterogeneous presentation pattern comprises a diagnostic
challenge, not uncommonly confused with a tumor accompanied by inflammation (Deramecourt et al., 2009; Nagata
et al., 2010; Nam, Choi, Kim, & Cho, 2011; Riela, Sires, &
Penry, 1991; Sun et al., 2014). Nonetheless, the CT displaying apparent normalization of the right temporal involvement flies in the face of a multicentric tumor, though this
technique is less sensitive than MRI in capturing subtle
alterations. Moreover, an infarct was detected in the territory of the left medial cerebral artery. On the other hand, in
order to impute this lesion to limbic encephalitis, it would
have to be confirmed by cerebrospinal fluid analysis, since
imaging is not so specific as to be able to guarantee it
without this datum. However, the patient’s general status
precluded further complementary testing.

All these lead us to believe that finding reversible brain
changes on the margin of the main mass is suggestive of
postictal encephalitis (with transient seizure-induced brain
changes) following nonconvulsive seizures. In fact, epilepsy is
the symptom that is more common with gliomas, occurring in
approximately half of all patients (van Breemen et al., 2009).
However, this clinical suspicion cannot be confirmed without
performing an electroencephalogram. In the case of our
patient, the reason for not expanding the study with this
test and not administering anticonvulsants was threefold: (1)
the clinical course appeared to be psychotic in its timeline and
time pattern and improved with neuroleptic treatment; (2) the
changes on the MRI were temporary and were interpreted as
possibly inflammatory; and (3) the aggressiveness of the glioblastoma multiforme made it difficult to carry out further
examinations. Nevertheless, we consider that occult epilepsy
could be a plausible diagnosis.
In fact, the most widely studied cases of hyperreligiosity are
those that occur in individuals with epilepsy, principally of the
RTL. A highly conspicuous trait of these patients is that they
may associate especially rich, upsetting, or intense spiritual
experiences (Devinsky & Lai, 2008). For example, in 1970,
Kenneth Dewhurst and A. W. Beard reported the case of a
bus conductor from London who suffered an epileptic seizure
(ecstatic) of the RTL while collecting tickets from the passengers and, at that precise instant, he felt that he had suddenly
found himself in Heaven, telling the surprised passengers
about his elation. The patient went through various phases,
from mystical rapture, serene religious feeling, and the loss of
faith several years afterward (Dewhurst & Beard, 1970). Most
reports coincide in that the subjects perceive light and being
transported to a luminous, expansive, highly meaningful reality with peace, harmony, hope, peace, and ecstasy in which
the spirit is freed from earthly and bodily constraints (Devinsky
& Lai, 2008). These spiritual experiences may be deistic,
depending on the subject’s personal elaboration or cultural
substrate. It has been estimated that approximately 1% of

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temporal lobe epilepsy sufferers experience ictal religious episodes (Kanemoto & Kawai, 1994). These patients have
reported diverse experiences, from very intense emotions
about the close presence or vision of the Divine to auditory
hallucinations of the voice of God, apparitions of divine figures, messages to be obeyed, or divine mandates to be fulfilled that, on rare occasions, are criminal or repetitions of
religious discourses. In these cases, the mystical experiences
are frequently emotionally intense, with theological ruminations, flashbacks, numinous auras, states of deep religious
conviction, feeling the presence of or becoming one with
the Universe or with the eternal (Landtblom, 2006). Often,
the religious personality in these cases is unorthodox and
exuberant, not uncommonly having paranormal content and
multiple deviations from standard religions (Waxman &
Geschwind, 1974). Moreover, electroencephalographic studies
have been conducted in Carmelite nuns who have demonstrated that mystical experiences are measured by striking
changes in the power or coherence of their brain waves
(Beauregard & Paquette, 2008).
In the case of postictal encephalitis, the physiopathological
substrate of the MRI alterations would be related to the vascular and metabolic response and would correspond to vasogenic and cytotoxic edema, respectively. There are also
indications that would suggest the coexistence of common
genetic mechanisms and pathways for the gliomatogenesis
and the epilepsy associated with these tumors (Berntsson,
Malmer, Bondy, Qu, & Smits, 2009; Sontheimer, 2008).
Peritumor adenosine kinase deregulation would play a role
in the cancer-related epileptogenesis (de Groot et al., 2012).
Of course, there is another credible explanation that has
been contemplated previously in the medical literature. It
postulates that the patient had a psychotic syndrome, periictal, or not, for which she ended up being treated (Kanemoto,
Oshima, Tadokoro, & Kanemoto, 2006). In fact, other authors
consider that the experiences associated with epileptic seizures are, more often than not, due to accompanying psychiatric co-morbidity (Connell, Keaveney, & Paul, 2013). On the
other hand, during interictal periods, a personality pattern is
commonly found, characterized by greater concern for highly
abstract philosophical issues, feelings of personal destiny, very
strong moral tendencies, or religious beliefs that frequently
contrast with the type of education received or the person’s
cultural context (Trimble & Freeman, 2006).
Pathological religious experiences have been reported in
relation to various diseases, such as autism, Parkinson’s disease, neurosyphilis, dementia, sleep deprivation, sensorial isolation, hallucinogenic drug use, obsessive-compulsive
disorder, manic-depressive disorder, schizophrenia, often as
part of dissociative states with altered self-identity
(Giaquinto, Bruti, Dall’Armi, Palma, & Spiridigliozzi, 2011).
Cases of hyperreligiosity have been reported in individuals
with atrophy of the RTL (Everhart, Watson, Bickel, &
Stephenson, 2015). However, none of these conditions appear
to play a role in this patient’s clinical manifestations. There is
also a field of research that postulates that the interindividual
differences in religious behavior may be founded in neurobiochemical variations such as the density of serotonin receptors
(Borg, Andree, Soderstrom, & Farde, 2014).

5

The severity of the disease presented here, in comparison
to the, a priori, less aggressive diagnosis of Sister John of the
Cross’ tumor (Salzman, 2000), did not expunge the moral issue
in the consultation that had been raised in the book; that is,
whether or not it is advisable to reverse all of the clinical
symptoms, with no regard for their nature or for the fact
that they had become an unarguable source of serenity and
well-being (Glannon, 2005). In fact, patients who undergo
mystical experiences speak of similar accompanying feelings
of pleasure or ecstasy (Stefan et al., 2004). The medical literature contains several examples of how effective treatment of
the underlying organic pathology is capable of mitigating the
episodes of abnormal behavior or psychiatric disturbance
associated with them (Filley & Kleinschmidt-DeMasters, 1995).
Certainly, it is true that medication exerted a similar effect in
this case. As the neuroleptics and cancer treatment started to
have their effect, we saw how the symptoms began to remit.
From this clinical observation, two main ideas have stood
out. First of all, there is the fact that religion is a phenomenon
that emerges from the brain and that depends on a complex
neural network, the effective functioning of which has been in
the process of fine-tuning since the dawn of human civilization (Schmidt, 2010). The subtle neuronal equilibria that generate the spiritual phenomenon are susceptible to becoming
disarranged in different ways due to the altering of any of the
brain circuit hubs (Paloutzian & Park, 2014). Second is the issue
of the constitution of the true self, which should at the very
least be fruit of the individual’s conscious legitimation of
themself, of their interests, and of their place in the world
(Frankfurt, 1988). In the case of our patient, it is clear that the
religious experience represented a fracture that did not form
part of the prior argumentarium of her life; that it was not
preceded by a gradual change in her thinking and acting, nor
was there any kind of trigger or reason except for the disease,
and hence, it can be considered a clearly pathological
experience.
It is worth asking oneself how often the behavioral alterations and, specifically, hyperreligiosity as an isolated symptom
of debut, occur in brain tumors. For years, it has been known
that some central nervous system diseases, including tumors,
make their clinical debut in the form of personality changes
(Partlow, del Carpio-O’Donovan, Melanson, & Peters, 1992), hallucinations, psychosis (Shah, Gordon, Bregy, Shah, & Komotar,
2014), and other complex disturbances in perception.
Given that most reports are single clinical case reports,
drawing conclusions as to incidence can be challenging,
although one review concluded that some 22% of all brain
tumors may debut with psychotic symptoms that are difficult
to associate with concrete topographies (Madhusoodanan et al.,
2010). Moreover, it is possible that these kinds of symptoms are
underdiagnosed when they are mild and, in the case of brain
tumors, because patients are not often asked in detail about
their experiences or the spiritual aspects of their diseases.
With respect to associated symptomatology, neurobehavioral disorders can, in fact, comprise the presentation of a
glioma (Blustein & Seeman, 1972) and can improve when
treated (Filley & Kleinschmidt-DeMasters, 1995). Autoscopy
(the individual sees themselves from outside of their own
body) (Devinsky, Feldmann, Burrowes, & Bromfield, 1989),

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A. CARMONA-BAYONAS ET AL.

states of pleasure, ecstasy, or well-being (Stefan et al., 2004),
numinous auras, which are those that are suggestive of phenomena having a spiritual intent or religious content, or
metaphysical in nature (Dolgoff-Kaspar et al., 2011), as well
as other premonitory or other kind of states, have been
reported in relation to epileptic seizures and can even improve
the decline in quality of life in certain pathologies (Giovagnoli,
Meneses, & da Silva, 2006).
Religion is one of the most surprising biocultural adaptations
of nature (Harris & McNamara, 2008). It is a complex cognitive
process, product of the activation of several circuits of the
neocortex, in which phenomena are often attributed to some
kind of divinity, conceived of as being infinite and eternal, and
by means of a causal chain, becomes the agent responsible for
each religious experience (Proudfoot & Shaver, 1975). The neurobiochemical foundations of religion continue to be unknown,
although the latest findings suggest that our brain might be
programmed for religious experience (Fingelkurts &
Fingelkurts, 2009). The presence of spiritual beliefs in all cultures, ages, civilizations, races, and geographies suggests the
presence of neurological correlates (Devinsky & Lai, 2008). It is
clear that all subjective human experience ultimately resides in
the brain, the neural networks of which are responsible for all
emotion and thought. Thus, neurological bases or patterns
have been sought to shed light on this phenomenon, although
they are never assumed to be a full description of it. In this
regard, religiosity involves many facets of human cognitive and
emotional activities, such as language, reasoning, joy, wonder,
etc., and there may be areas or connections that are especially
affected (Saver & Rabin, 1997).
In the case of our patient, the tentative search for possible
topographic localizations or neurophysiological correlates is
complex, despite how conspicuous the mass was and the possible epileptic etiology. Glioblastomas multiformes are highly invasive tumors that are not circumscribed to specific topographic
zones; rather, they outgrow the territories in which they arise.
These types of clinical symptoms, therefore, will rarely present as
a purely psychiatric disorder and, in fact, will tend to associate
with more comorbidity or with more complex polysyndromic
situations as the disease progresses (Sokolski & Denson, 2003).
From this perspective, the perfect correlation between the location of the lesion and behavior is not possible, since the inflammation, bleeding, and edema complicate even further the
clinical-anatomic correlation. In contrast, for the paucity of data
that exist, the neurophysiological substrate has been described
fairly consistently in the literature for years.
More than 100 years ago, the American philosopher and
psychologist William James outlined two varieties of religious
experiences. On the one hand are those transmitted by
family and society that generally materialize as complying
with moral precepts, identification of group observance of
dogmas, etc., whereas, on the other hand, there is another
kind of spiritual experience, even more intense or more
genuine in appearance if possible (James, 1985). In the
words of James, they would be “not as a dull habit, but as
an acute fever rather.” Surely this is reductionistic, and religion has other components such as altruism, consolation,
charity, hope, etc. Nevertheless, this approach could be
valid, since tentatively, albeit consistently, neuroscience has

found that in the former case, the anatomic correlate appears
to reside in the frontal lobes, whereas in the latter case, it
would generally be temporal lesions. However, this may be a
simplified approach. Thus, one study of functional MRI performed on Carmelite nuns to identify the neural correlates of
religious experience detected multiple brain areas (e.g., right
inferior and superior parietal lobules, right caudate, right
medial orbitofrontal cortex, right middle temporal cortex,
left medial prefrontal cortex, left anterior cingulate cortex,
left inferior parietal lobule, left insula, left caudate, and left
brainstem) involved in various aspects of religiosity
(Beauregard & Paquette, 2006). The authors stated that this
multiplicity of locations is not surprising given the fact that
these experiences are complex and multidimensional.
In the woman whose case we report, there was extensive
involvement of the limbic lobe and anterior pole of the RTL. In
effect, the temporal lobes, particularly the RTLs (Devinsky &
Lai, 2008), have been cited reiteratively in the development of
ecstatic mystical experiences (Tucker, Novelly, & Walker, 1987;
Willmore, Heilman, Fennell, & Pinnas, 1980), while other components of religious experience are related more with other
topographical locations. In the case of Sister John of the Cross,
it is possible that there was a disturbance at the level of the
connection with the right angular gyrus that is partially
responsible for identity and spatial orientation. A lesion at
this level hinders the patient’s ability to establish the limits
between self and the rest of the universe (Spitoni et al., 2013).
Thus, the RTL is critical for the perception of intense spiritual
phenomena, similar to William James’ description. Other
regions reported in the literature as anatomic substrates of
hyperreligiosity are the limbic system (Trimble & Freeman,
2006) and the hippocampus. The MRI volumetric studies
reveal that patients with hyperreligious criteria have a significantly smaller right hippocampus, with no differences in the
size of the amygdala (Wuerfel et al., 2004). The anterior rostral
cingulate cortex has been linked to altruism.
In contrast, the frontal lobe is the phylogenetically youngest area of the central nervous system and plays a key role in
the organization and integration of behavior (Mesulam, 1986).
There are three types of frontal syndromes, depending on the
precise location, and when involvement is bilateral, the syndrome is all the more dramatic (Filley & KleinschmidtDeMasters, 1995). It is well known that disturbances of more
complex activities, such as conceptualization or personality,
occur especially when there are prefrontal lesions
(Campanella, Shallice, Ius, Fabbro, & Skrap, 2014). The frontal
lobes have not been associated with such vivid religious
experiences but are responsible for personality, including
complex aspects such as politics, behavior, social relation,
introspection (Brower & Price, 2001; Johnson et al., 2002), or
greater religious interest as a personality trait (Floris et al.,
2012). In our case, MRI abnormalities in the temporal lobe
preclude the assumption that the frontal lobe lesion is the
cause of the religious phenomena. However, the conspicuous
abulia, apathy, and personality change observed in our patient
are clear characteristics of frontal syndromes. Thus, in one
series, 10% of the patients with fronto-temporal dementia
underwent dramatic changes with respect to their previous
political, social, or religious ideas. The majority of these

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subjects presented involvement of the nondominant frontal
lobe (Miller et al., 2001).
In general, we are dealing with scenarios in which the
perception of self and of its limits is affected by reason a
frontal lesion that provides the substrate of pathological religious experiences in which the individual will have the feeling
of having coalesced with everything or with the Divine. Hence,
the involvement of frontal medial cortex is necessary to be
able to discern in the mind of others, which can be extended
to include the ability to discern in the mind of God (Stuss,
Gallup, & Alexander, 2001).
The areas of relation of the parietal lobes have also been
implicated in the appearance of pathological religious experiences (Crescentini, Aglioti, Fabbro, & Urgesi, 2014). One brain
perfusion study carried out in Tibetan monks while they meditated found that the substrate of some mystical experiences
was the deafferentation of the postero-superior parietal lobe.
This region has to do with spatial orientation and the perception of oneself in relation with the rest of the Universe
(Newberg et al., 2001). In their pathological aspect, alterations
in this area would give rise to a tremendous sense of uniting
with Eternity and the Devine. Likewise, Azari et al. demonstrated the importance of a preestablished frontal-parietal
circuit (Azari et al., 2001). The religious experience would
occur when the products of this circuit are in consonance
with the subject’s previous religious belief system (Azari
et al., 2001). According to this, religion would not only always
be an emotional but also cognitive experience and, therefore,
a truly human phenomenon.
When taken all together, we find that multiple structures are
involved, including the limbic system (e.g., the amygdala), portions of the basal ganglia, the RTL, and the prefrontal cortex,
particularly on the right side, which are the hubs in the circuit of
religiosity. Key to these structures are the ascending serotoninergic system and the dopaminergic system. All of these regions are
highly interconnected. When it is stimulated in excess or affected
by some kind of disease, religious ecstasy takes place. When
cortical circuit activation prevails, religious ideations are the
result. In contrast, when the limbic system or the basal ganglia
are involved, we find obsessive ideations, changes in behavior
rituals, and increased interest in stereotyped religious practices,
such as prayer (Paloutzian & Park, 2014).
In short, several studies about exaggerated human behaviors, for instance, hyperreligiosity, time and again confirm
their correlation with temporal and frontal lobe areas of the
brain and with maladies such as epilepsy and cancer.
However, we have yet to fully understand the neurological
substrate of religiosity, taken to mean a more stable, daily, and
permanent adhesion to a belief system that is positively associated with indicators of psychological and social well-being
(satisfaction with life, positive affect, sense of family, and
morality), and whether specific neuroanatomical variants
might be hidden behind it.

Acknowledgments
Thanks to Priscilla Chase Duran for editing and reviewing the original text.
Dedicated to Oliver Sacks for his encouragement several months ago to
publish this case report.

7

Disclosure statement
No potential conflict of interest was reported by the authors.

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