Theoretical foundations underlying neurosurgical interventions
for the treatment of intractable OCD
Joey Mo
1104542
PSYCI 511
Dr. Esther Fujiwara
Joey Mo • 1104542
PSYCI 511 • Dr. Esther Fujiwara
Introduction
Obsessive-compulsive disorder (OCD) is a debilitating illness comprised of recurrent,
worrisome obsessions, and/or the excessive compulsions that accompany them (APA, 2000; Berlin,
Hamilton, & Hollander, 2008; Liu et al., 2008; Maia, Cooney, & Peterson, 2008; Micallef & Blin,
2001). It severely affects the quality of life of patients, causing not only marked distress but also
significant interference in social, occupational, and interpersonal functioning (APA; Micallef et al.;
Mishra, Sahoo, & Mishra, 2007; Schruers, Koning, Luermans, Haack, & Griez, 2005). As the 11th
leading cause of non-fatal burden of disease in the world, OCD is exceedingly destructive and
disabling, and represents an enormous financial cumbrance (Ayuso-Mateos, 2000; Greenberg et al.,
2003).
While many conventional interventions such as pharmacotherapy or behavioral therapy exist
for the treatment of OCD, approximately 30% of patients fail to respond to these treatments (Anderson
& Booker, 2006; Berlin et al., 2008; McDonough & Kennedy, 2002; Mishra et al., 2007; Rück,
Edman, Nyman, & Håkan, 2008; Schruers et al., 2005). In addition to those who fail conventional
therapy outright, 40-60% experience only a partial response or an intolerance to SSRIs, and 20-30%
are unable to find relief from behavioral therapies (Berlin et al.; Greenberg et al., 2003; Liu et al.;
Mishra et al.; Schruers et al.). Furthermore, it is estimated that 10% of all OCD patients are resistant to
optimal pharmacotherapy (augmentation strategies, combination therapies) and long-term behavioral
therapies, leaving them with chronic intractable OCD that incapacitates their psychosocial, role, and
even physical functioning (Greenberg et al.; Kondziolka & Hudak, 2008; Schruers et al.). In the event
of intractable OCD, surgical interventions such as ablative neurosurgery and deep brain stimulation
(DBS) are then considered as last-resort treatments, offering lasting relief for 50-70% of these patients
(APA, 2000; Berlin et al.; Eljamel, 2008; Greenberg et al.; Kim & Lee, 2008; Liu et al.; McDonough et
al.; Mishra et al.; Rück et al.; Schruers et al., ). Neurosurgical treatments thus represent important
additions to the medical arsenal used in the treatment of OCD.
1
Joey Mo • 1104542
PSYCI 511 • Dr. Esther Fujiwara
To begin, current issues surrounding the neuropathology of OCD will be presented. This will
include evidence of cerebral volumetric abnormalities, disruptions in metabolic activity, and alterations
in neuronal communication & viability in circuits associated with the disease. Common neurosurgical
techniques that aim to rectify these dysfunctions will then be considered, and their theoretical
ameliorative mechanisms will be examined.
The Cortico-Striatal-Thalamo-Cortical (CSTC) Circuit as a Neural Correlate for OCD
Surgical treatment of OCD takes on a neuroanatomical approach to a psychiatric disorder by
attempting to rectify abnormalities in specific CSTC loops and their communication with affective
limbic structures (Berlin et al., 2008; Cannistraro et al., 2007; Greenberg, Murphy, & Rasmussen,
2000; Maia et al., 2008; Nakamae et al., 2008; Swoboda & Jenike, 1995; Szeszko et al., 2005). This set
of anatomically and functionally interconnected nodes have been strongly implicated in OCD, and
include the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), caudate nucleus, dorsomedial
nucleus (DMN) of the thalamus, and the white matter (WM) tracts that connect them (Fig. 1).
Although the biological etiology of OCD remains unknown, converging evidence suggests that these
areas play a central role in the pathophysiology of OCD (Micallef et al., 2001).
Fig. 1 A diagrammatic representation of the neuroanatomical correlates of
OCD. The CSTC loop referred to primarily consists of the prefrontal cortex
(OFC), striatum (caudate), and the DMN of the thalamus, connected both
functionally and anatomically with the limbic system (ACC). Maia et al.
(2008) refer to this particular loop as the “OFC/ACC cortical-basal gangliathalamo-cortical loop”, in recognition of the fact that several parallelrunning CSTC loops exist, but the aforementioned loop is the only one with
major relevance to OCD (p. 1255).
Due to the connectivity of structures within the basal ganglia, there is a
direct path that leads to net activation of the CSTC loops, as well as an
indirect path that results in net inhibition (Afifi, 2003; Herrero, Barcia &
Navarro, 2002; Liu et al., 2008; Narayan et al., 2008). This has been
studied extensively in movement disorders, where motor CSTC loops are
concerned, and is a comparable model for dysfunctional activity in the
OFC/ACC CSTC loop for OCD (Afifi; Maia et al., 2008).
The OFC is a well-studied structure in OCD research and findings on its integrity have been
consistently replicated. As an area known to be involved in adjusting behavior during changing
conditions, inhibition of prepotent motor responses, and assigning reward value to actions and
decisions, the OFC has been an obvious target for scrutiny (Berlin et al., 2008; Christian et al., 2008;
2
Joey Mo • 1104542
PSYCI 511 • Dr. Esther Fujiwara
Fontenelle, Mendlowicz, Mattos, & Versiani, 2006; Torregrossa, Quinn, & Taylor, 2008). Gray matter
(GM) volumes have been shown to be decreased in studies using region-of-interest (ROI) approaches
(Berlin et al.; Maia et al., 2008; Micallef et al., 2001). Various voxel-based morphometry (VBM)
studies corroborate this evidence, although a smattering of recent studies present controversial findings
to the contrary (Christian et al.; Maia et al., Narayan et al., 2008). These disagreements can be best
explained by the enhanced level of detail in the analysis provided by VBM – the possibility that
different subregions within the OFC can have differential volume changes (Christian et al.; Fontenelle
et al.; Maia et al.; Narayan et al.). The general consensus is that a majority of studies indicate an
overall volume deficiency in OCD that correlates with increased symptom severity (Maia et al.).
The caudate nucleus has been another structure strongly tied into the pathophysiology of OCD,
and comprises an important hub within the OFC/ACC CTSC loop. While structures in the basal
ganglia have been classically associated with motor disorders, the head of the caudate has been
associated with more cognitive functions: The reward and inhibition of particular behaviors, the ability
to shift attention, and higher order control of movement initiation (Afifi, 2003; Herrero et al., 2002).
Proton magnetic resonance spectroscopy (1H-MRS) studies measuring N-acetyl-aspartate (NAA)
levels, an indicator for neuronal viability, in the caudate show mixed results (Maia et al., 2008).
Studies of volume (both ROI and VBM) concerned with this structure have also produced a variety of
conclusions, with the majority indicating no significant volume change (Christian et al., 2008;
Greenberg et al., 2000; Micallef et al., 2001; Narayan et al., 2008; Szeszko et al., 2005). Differences in
the findings, however, can most likely be attributed to volumetric studies concentrating on total
caudate volume. The only neuroanatomically relevant portion of the caudate involved in OCD are the
fibers running through the head of the caudate; these are the only tracts participating in the OFC/ACC
CTSC loop (Maia et al.). To date, only a few studies have focused on analyzing head of caudate
volumes, showing either no significant change or an increase in GM volume in this area (Berlin et al.,
2008; Maia et al.). Future studies focusing on this specific subregion of the caudate will be able to
3
Joey Mo • 1104542
PSYCI 511 • Dr. Esther Fujiwara
delineate whether OCD results in a heterogeneous spectrum of caudate abnormalities, specific GM
increases in the head of the caudate, or whether these are simply confounds of chronic
pharmacotherapy or comorbidity (Berlin et al.).
The DMN of the thalamus represents another key junction in the OFC/ACC CSTC loop that is
volumetrically altered in OCD. The DMN has a history in both neuropathology and neurosurgery,
being one of the primary targets affected by the notorious Freeman-Watts prefrontal lobotomy
(Glannon, 2006; Gostin, 1980; Hendelman, 2000). As a result, the DMN is known to be involved in
motivation, drive, and emotional affect. These are broad behavioral and cognitive categories that are
implicated in several diseases including memory disorders, anxiety disorders, and schizophrenia, for
which the prefrontal lobotomy was most widely used (Conrad, Wegener, Geiser, Imbierowicz, &
Liedtke, 2008; Gostin; Haut, Young, & Cutlip, 1995; Nolte, 2002). Both ROI and VBM studies
suggest that increases in thalamic volume exist in OCD, and that volumes share a positive correlation
with symptom severity (Christian et al., 2008; Maia et al., 2008, Micallef et al., 2001).
The ACC is the final component of the OFC/ACC CSTC loop, and has been known to be
involved in cognitive-emotive interactions and attention to behaviors (Devinsky, Morrell, & Vogt,
1995). While its role in cognition is well-studied, its presence in the pathophysiology of OCD is
perplexing, as there seems to be no agreement on the nature of GM volume changes. ROI studies
conducted in adults with OCD consistently find no significant change in ACC volume, while the same
studies in children find marked increases in volume (Christian et al., 2008; Maia et al., 2008). Further
compounding the confusion is that VBM studies show consistent decreases in both child and adult
ACC volumes (Maia et al.). 1H-MRS, which is considered to be a more sensitive measure of neuronal
volume, indicates decreased NAA levels in the ACC, suggesting that perhaps only low-grade
abnormalities in GM density exist within the ACC (Maia et al.).
It is important to consider that despite knowledge of GM changes to structures within the
CSTC loop, we cannot ascertain whether these alterations are causal or compensatory. It is also
4
Joey Mo • 1104542
PSYCI 511 • Dr. Esther Fujiwara
difficult to interpret what GM volume differences indicate. For example, we cannot be certain as to
whether a hypertrophic lesion suggests increased activity/facilitation of neuronal transmission or if it
signifies impaired communication due to dysfunctional neuronal pruning (Christian et al., 2008). It is
therefore imperative to consider functional studies in addition to structural ones in order to obtain a
better sense of the true nature of the altered OCD circuit.
The body of evidence implies that hyperactivity within the OFC/ACC loop is strongly
contributory to the pathogenesis of OCD. Functional neuroimaging studies have found increased
metabolic activity during rest in the ACC, head of the caudate, OFC, and thalamus, which increased
during symptom provocation and decreased with successful treatment (associated with positive
behavioral recovery from symptoms) (Cannistraro et al., 2007; Christian et al., 2008; Fontenelle et al.,
2007; Maia et al., 2008; Narayan et al., 2008; Szeszko et al., 2005). Cognitive activation studies mirror
these findings, as do 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) studies under
the same conditions (Berlin et al., 2008; Greenberg et al., 2000; Maia et al; Micallef et al., 2001; Rauch
et al., 2001; Swoboda et al., 1995). The general theory of OCD proposes that a net increase in resting
activity exists, due in part by increased input to the OFC/ACC CSTC circuit, but also because of an
imbalance favouring the direct pathway from the striatum onward (Fig. 2).
Fig. 2 A diagrammatic representation of the
corticostriate projections and their relative
influences upon each node (Herrero et al., 2002;
Lipsman, Neimat, & Lozano, 2007). Text in blue
indicates volumetric changes at each site in OCD,
while red indicates functional activity.
Volumetric and functional studies suggest that
hyperactivity is the net effect in the system, and
that volume changes share a correlation with
changes in relative activity. Some areas remain
open for further investigation (I.e. Few studies
have examined the globus pallidus/substantia nigra
and the efficacy of anteromedial pallidotomy), but
surrounding evidence infers a trend towards
volumes that increase net CSTC activity.
Neurosurgical Interventions for the treatment of intractable OCD
The realization that net hyperactivity exists within the OFC/ACC CSTC circuit has led to the
development of neurosurgical techniques aimed at disrupting activity to normal levels by severing
5
Joey Mo • 1104542
PSYCI 511 • Dr. Esther Fujiwara
improper communication at important nodes. Early surgeries included the infamous prefrontal
lobotomy and the dorsomedial thalamotomy; the former causing marked personality blunting, sullying
the name of neurosurgery to this day, and the latter causing death by hemorrhage in ~10% of patients
due to the thalamus being highly vascularized (Glannon, 2006; Gostin, 1980; Greenberg et al., 2003).
With the advent of modern day stereotactic instruments and knowledge from structural and functional
neuroimaging studies regarding the nature of the CSTC loop, current ablative procedures are much
more refined, widely performed, and no longer deemed experimental (Greenberg et al.). Four common
surgeries exist: Anterior capsulotomy, anterior cingulotomy, subcaudate tractotomy, and limbic
leucotomy, which combines the techniques of anterior cingulotomy and subcaudate tractotomy (Fig. 3)
(APA, 2006; Berlin et al., 2008; Fontenelle et al., 2006; Greenberg et al.; Lopes et al., 2004). Current
experimental therapies also include DBS in the same region as the anterior capsulotomy, which has
been touted to be a possible replacement for ablative neurosurgery due to its efficacy and reversibility
(APA, 2000; American Psychological Association; Berlin et al., Eljamel, 2008).
Fig. 3 WM tracts involved in common
neurosurgical procedures for OCD (McGraw
& Nadar, 2007; Greenberg et al.). Markings
in white denote areas of surgical lesioning.
The image on the left is a coronal section –
lesions indicate a bilateral capsulotomy
severing the anterior limb of the internal
capsule (ALIC). The image on the right
shows a sagittal section – topmost lesion
indicates a bilateral cingulotomy severing
the anterior portion of the cingulum bundle
(CB); bottom lesion indicates a subcaudate
tractotomy beneath the caudate head in
the substantia innominata.
The anterior cingulotomy is the most common neurosurgical procedure for OCD performed in
the United States, offering an efficacy rate of 27-57% in global improvement and having a favorable
safety profile (APA, 2006; Lopes et al., 2004; Greenberg et al., 2003). Using MRI guidance (prior to
1991, ventriculography was used), lesions are placed bilaterally within the CB by way of
thermocoagulation or radiofrequency probes (APA; Eljamel, 2008; Greenberg et al.; Kim et al., 2008;
Lopes et al.). Though the exact mechanism by which anterior cingulotomy operates is largely
6
Joey Mo • 1104542
PSYCI 511 • Dr. Esther Fujiwara
unknown, it is hypothesized that it interrupts limbic connections between the OFC, the ACC, and the
ACC’s connections to the caudate nucleus (Greenberg et al.; Maia et al., 2008). Diffusion tensor
imaging (DTI) studies focusing on the CB have been inconclusive on this matter: Nakamae et al.
(2008) and Yoo et al. (2007) have recently shown no significant difference in this tract, Cannistraro et
al. (2007) discovered higher fractional anisotropy (FA) in the left CB (which could indicate a
facilitation of information transfer), and both Cannistraro et al. and Szeszko et al. (2005) found
decreased FA in the right CB (which might indicate decreased information transfer due to pathological
demyelination or tract directional incoherence). While these studies show inconsistent results, it is
clear that a WM abnormality exists, a finding that is supported by genetic studies implicating
myelination-associated genes OLIG21 and MOG2 (Cannistraro et al.; Nakamae et al.). While the
evidence for the use of the anterior cingulotomy procedure is rather empirical and almost
serendipitous, anterior cingulotomy is an effective surgical method that is able to rectify inappropriate
communication within the limbic compartment of the OFC/ACC CSTC circuit (Greenberg et al.).
Future DTI studies examining WM tracts will undoubtedly divulge important clues to the interactions
of CSTC nodes, both increasing knowledge of the pathophysiology of OCD, and uncovering the
mechanism behind this technique.
Anterior capsulotomy also targets an important WM tract connecting points in the OFC/ACC
CSTC circuit; the anterior limb of the internal capsule (ALIC) is bilaterally lesioned in this procedure
(Berlin et al., 2008; Greenberg et al., 2003, Liu et al., 2008; Rück et al., 2008). This can be done by
creating lesions with radiofrequency thermocoagulation or by gamma knife capsulotomy, a novel
technique that uses converging gamma rays to create a lesion without the need for craniotomy (Lopes
et al., 2004; Greenberg et al.). Capsulotomies offer an extremely positive 56-100% global rate of
improvement and gamma knife capsulotomies are an important upgrade to the surgery, creating a
1
OLIG2: Oligodendrocyte lineage factor 2 – “an essential regulator in the development of WM producing cells”
(Cannistraro et al., 2007, p. 444; Nakamae et al., 2008)
2
MOG: Myelin oligodendrocyte glycoprotein – “encodes for an integral membrane protein expressed in oligodendrocytes
and myelin sheaths” (Cannistraro et al., 2007, p. 444)
7
Joey Mo • 1104542
PSYCI 511 • Dr. Esther Fujiwara
smaller lesion volume and thus decreased prevalence of adverse events (Lopes et al.; Greenberg et al.).
Anterior capsulotomy acts by halting reciprocal communication between the DMN of the thalamus and
the OFC, and also destroys some fibers communicating with the ACC (Lopes et al., Greenberg et al.,
Maia et al., 2008). Liu et al. have previously shown that bilateral capsulotomy is effective in reducing
glucose metabolism in OFC and caudate in FDG-PET, and Greenberg et al. (2000) report that frontal
metabolism and OCD symptoms decrease together following anterior capsulotomy. In tandem with
these results, Yoo et al. (2007) reported increased FA in the WM surrounding the striatum and
thalamus in DTI, and Cannistraro et al. (2007) found increased left FA directly in the ALIC,
suggesting OCD patients have a facilitation of communication that results in hyperactivity. By
severing the ALIC activity is normalized within the CSTC loop, which leads to symptomatic relief.
An exciting new advancement to anterior capsulotomy involves DBS, which calls for
implantation of electrodes within the ALIC (Berlin et al., 2008; Lopes et al., 2004). DBS in this region
is postulated to operate similarly to ablative capsulotomy, only inhibition of the circuit uses high
frequency electrical stimulation rather than tissue destruction. Berlin et al. propose a number of
mechanisms of action, including “release of inhibitory neurotransmitters, synaptic inhibition,
depolarization blockage, synaptic fatigue/depression, neural jamming, and stimulation-induced
modulation of pathologic network activity”; to recapitulate, the mechanism of blockade is unknown (p.
186). As a result of its novelty and unspecified mechanism, DBS is still tagged as an experimental
therapy. Regardless, reception of DBS has been positive: Gabriëls, Nuttin, and Cosyns (2008) found
that 82% of the members of the Scientific Society of Psychiatrists would consider referral for DBS, as
opposed to 44% for capsulotomy. DBS offers an attractive alternative to anterior capsulotomy,
especially since it performs just as well as capsulotomy, modulation can be adjusted for optimal effect,
and if effects are not shown the procedure is entirely reversible (Eljamel, 2008).
Subcaudate tractotomy involves lesioning the substantia innominata in the WM ventral to the
head of the caudate nucleus, which effectively severs communication between the OFC, thalamus, and
8
Joey Mo • 1104542
PSYCI 511 • Dr. Esther Fujiwara
the ACC (Berlin et al., 2008; Greenberg et al., 2000; Greenberg et al., 2003; Kim et al., 2008; Lopes et
al., 2004). It carries a 33-67% global improvement rate, an extremely low 0-5% adverse reactions rate,
and strongly decreases risk for suicide (Lopes et al.; Greenberg et al., 2003). Theoretically, subcaudate
tractotomy lowers hyperactivity by anatomically and functionally limiting activity traversing its fibers.
It has been shown that secondary degeneration of the ALIC occurs following subcaudate tractotomy - a
functional ‘lesion’ of the ALIC occurs as a result of disrupted communication through the DMN of the
thalamus (Greenberg et al., 2000; Maia et al., 2008). Micallef et al. (2001) have noted that many
successful neurosurgeries in the treatment of OCD share lesions in the right ALIC, and have suggested
that subcaudate tractotomy operates in the same manner as capsulotomy to provide its ameliorative
qualities, albeit indirectly. Perhaps its indication for use in OCD, depression, and other intractable
anxiety disorders hints that it is a ‘dirtier’ surgery than capsulotomy, as gamma knife capsulotomy is
almost exclusively used for intractable OCD (Greenberg et al., 2003). As it is one of the younger
ablative techniques for OCD, future research will be able to tell whether subcaudate tractotomy and
anterior capsulotomy operate by the same mechanism and if either holds any added benefit over the
other (Greenberg et al.).
Concluding Remarks: The Bigger Picture
While neurosurgical techniques for OCD have been effective in treating a high percentage of
intractable OCD cases, it is still important to consider that several shortcomings still exist. Most of
these procedures were developed early in the 20th century and rely almost exclusively upon empirical
evidence and through a limited understanding of the connectivity of structures underlying the disease
(Maia et al., 2008). Though our knowledge of the mechanisms behind the curative properties of these
neurosurgical procedures is still rather rudimentary, with increased knowledge from research studies
and the development of superior technologies, the creation of focal disruptions that are reversible or
that exclude the need for craniotomy has been possible. Tightly controlled studies have previously
been ethically impossible, but with the introduction of gamma knife surgeries and DBS, the ability to
9
Joey Mo • 1104542
PSYCI 511 • Dr. Esther Fujiwara
compare against sham surgeries and placebo controls is now a reality and will undoubtedly offer new
perspectives as to the efficacy of these treatments in years to come.
The future holds a much better understanding of the pathophysiology of OCD, which will allow
for selection of more appropriate and effective targets that have fewer side effects. For instance,
anteromedial pallidotomy has very recently been suggested as a novel technique (see Fig. 2), and the
nucleus accumbens seems to be a hub connecting fibers targeted by all of the aforementioned lesions
(Berlin et al., 2008; Lopes et al., 2004). It cannot be disregarded that improvement occurs gradually
following surgery, and that evolution of the lesion likely plays a large role in this process (Greenberg
et al., 2000). Use of pharmacotherapies have been shown to be enhanced following surgery, which
suggests that there is still much to be learned with regards to how the OFC/ACC CSTC circuit
operates, and what other areas are also involved (Greenberg et al.; Maia et al., 2008). Several
neuropsychological studies are also examining the neural correlates of specific cognitive deficiencies
in the hopes of being able to predict which lesion areas may be most appropriate for the spectrum of
symptoms presented (Christian et al., 2007; Fontenelle et al., 2007). While today’s treatment of OCD
seems adequate, it is the dream that one day we might be able to target specific areas to resolve
particular cognitive dysfunctions, maximize efficacy so that effects are immediate, and minimize any
side effects from the procedure itself or resulting cognitive/personality alterations.
Without a doubt, neurosurgical interventions confer an exciting viewpoint with which to
approach the hotbed of research that accompanies this affliction. The results of treatments using these
techniques will uncover clues to the mystery that surrounds the pathogenesis of OCD. Conversely,
neurosurgical interventions provide patients with intractable OCD renewed optimism that ablative
neurosurgery or DBS may relieve them of their symptoms and provide them a better quality of life.
10
Joey Mo • 1104542
PSYCI 511 • Dr. Esther Fujiwara
References
Afifi, A. K. (2003). The basal ganglia: A neural network with more than motor function. Seminars in
Pediatric Neurology, 10(1), 3-10.
American Psychiatric Assocation (APA) (2000). Diagnostic and statistical manual of mental disorders
(4th ed., Text revision). Washington, DC: Author.
American Psychiatric Association (APA) (2006). Practice guideline for the treatment of patients with
obsessive-compulsive disorder: Neurosurgical stereotactic lesion procedures. American
Psychiatric Association Practice Guidelines for the Treatment of Psychiatric Disorders:
Compendium 2006 (chap. 4). doi:10.1176/appi.books.9780890423363.149114
Anderson, S. W., & Booker, M. B. (2006). Cognitive behavioral therapy versus psychosurgery for
refractory obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci, 18(1), 129.
Ayuso-Mateos, J. L. Global burden of obsessive-compulsive disorder in the year 2000. Geneva, World
Health Organization (Global Program on Evidence for Health Policy (GPE): Global Burden of
Disease 2000) 2000.
Berlin, H. A., Hamilton, H., & Hollander, E. (2008). Experimental therapeutics for refractory
obsessive-compulsive disorder: Translational approaches and new somatic developments.
Mount Sinai Journal of Medicine, 75, 174-203.
Cannistraro, P. A., Makris, N., Howard, J. D., Wedig, M. M., Hodge, S. M. Wilhelm, S., et al. (2007).
A diffusion tensor imaging study of white matter in obsessive-compulsive disorder. Depression
and Anxiety, 24, 440-446.
Christian, C. J., Lencz, T., Robinson, D. G., Burdick, K. E., Ashtari, M., Malhotra, A. K., et al. (2008).
Gray matter structural alterations in obsessive-compulsive disorder: Relationship to
neuropsychological functions. Psychiatric Research: Neuroimaging, 164, 123-131.
11
Joey Mo • 1104542
PSYCI 511 • Dr. Esther Fujiwara
Conrad, R., Wegener, I., Geiser, F., Imbierowicz, K., & Liedtke, R. (2008). Nature against nurture:
Calcification in the right thalamus in a young man with anorexia nervosa and obsessivecompulsive personality disorder. CNS Spectr, 13(10), 906-910.
Devinsky, O., Morrell, M. J., & Vogt, B. A. (1995). Contributions of anterior cingulate cortex to
behaviour. Brain, 118, 279-306.
Eljamel, M. S. (2008). Ablative neurosurgery for mental disorders: is there still a role in the 21st
century? A personal perspective. Neurosurg Focus, 25, 1-6.
Fontenelle, L. F., Mendlowicz, M. V., Mattos, P., & Versiani, M. (2006). Neuropsychological findings
in obsessive-compulsive disorder and its potential implications for treatment. Current
Psychiatry Reviews, 2, 11-26.
Gabriëls, L., Nuttin, B., & Cosyns, P. (2008). Applicants for stereotactic neurosurgery for psychiatric
disorders: Role of the Flemish advisory board. Acta Psychiatr Scand, 117, 381-389.
Glannon, W. (2006). Neuroethics. Bioethics, 20(1), 37-52.
Gostin, L. O. (1980). Ethical considerations of psychosurgery: The unhappy legacy of the pre-frontal
lobotomy. Journal of medical ethics, 6, 149-154.
Greenberg, B. D., Murphy, D. L., & Rasmussen, S. A. (2000). Neuroanatomically based approaches to
obsessive-compulsive disorder: Neurosurgery and transcranial magnetic stimulation. The
Psychiatric Clinics of North America, 23(3), 671-686.
Greenberg, B. D., Price, L. H., Rauch, S. L., Friehs, G., Noren, G., Malone, D., et al. (2003).
Neurosurgery for intractable obsessive-compulsive disorder and depression: Critical issues.
Neurosurg Clin N Am, 14, 199-212.
Haut, W. H., Young, J., & Cutlip, W. D. (1995). A case of bilateral thalamic lesions with anterograde
amnesia and impaired implicit memory. Archives of Clinical Neuropsychology, 10(6), 555-566.
Hendelman, W. J. (2000). Atlas of Functional Neuroanatomy (1st ed.) Boca Raton, FL: CRC Press.
12
Joey Mo • 1104542
PSYCI 511 • Dr. Esther Fujiwara
Herrero, M., Barcia, C., & Navarro, J. M. (2002). Functional anatomy of thalamus and basal ganglia.
Child’s Nerv Syst, 18, 386-404.
Kim, M. C., & Lee, T. K. (2008). Stereotactic lesioning for mental illness. Acta Neurochir Suppl, 101,
39-43.
Kondziolka, D., & Hudak, R. (2008). Management of obsessive-compulsive disorder-related skin
picking with gamma knife radiosurgical anterior capsulotomies: A case report. J Clin
Psychiatry, 69(8), 1337-1340.
Lipsman, N., Neimat, J. S., & Lozano, A. M. (2007). Deep brain stimulation for treatment-refractory
obsessive-compulsive disorder: The search for a valid target. Neurosurgery, 61(1), 1-13.
Liu, K., Zhang, H., Liu, C., Guan, Y., Lang, L., Cheng, Y., et al. (2008). Stereotactic treatment of
refractory obsessive compulsive disorder by bilateral capsulotomy with 3 years follow-up.
Journal of Clinical Neuroscience, 15, 622-629.
Lopes, A. C., de Mathis, M. E., Canteras, M. M., Salvajoli, J. V., Del Porto, J. A., & Miguel,
E. C. (2004). Update on neurosurgical treatment for obsessive compulsive disorder. Rev Bras
Psiquiatr, 26(1), 61-65.
Maia, T. V., Cooney, R. E., & Peterson, B. S. (2008). The neural bases of obsessive-compulsive
disorder in children and adults. Development and Psychopathology, 20, 1251-1283.
Compulsive Disorder. J Neuropsychiatry Clin Neurosci, 11(2), 259-267.
McDonough, M., & Kennedy, N. (2002). Pharmacological management of obsessive-compulsive
disorder: A review for clinicians. Harvard Rev Psychiatry, 10(3), 127-135.
McGraw, T. & Nadar, M. (2007). [Stochastic DT-MRI Connectivity Mapping on the GPU]. Computer
Science and Electrical Engineering Dept., West Virginia University. Retrieved from
http://www.csee.wvu.edu/~tmcgraw/gpu/index.html
Micallef, J., & Blin, O. (2001). Neurobiology and clinical pharmacology of obsessive-compulsive
disorder. Clinical Neuropharmacology, 24(4), 191-207.
13
Joey Mo • 1104542
PSYCI 511 • Dr. Esther Fujiwara
Mishra, B., Sahoo, S., & Mishra, B. (2007). Management of treatment-resistant obsessive-compulsive
disorder: An update on therapeutic strategies. Ann Indian Acad Neurol, 10, 145-153.
Nakamae, T., Narumoto, J., Shibata, K., Matsumoto, R., Kitabayashi, Y., Yoshida, T., et al. (2008).
Alteration of fractional anisotropy and apparent diffusion coefficient in obsessive-compulsive
disorder: A diffusion tensor imaging study. Progress in Neuro-Psychopharmacology &
Biological Psychiatry, 32, 1221-1226.
Narayan, V. M., Narr, K. L., Phillips, O. R., Thompson, P. M., Toga, A. W. & Szeszko, P. R. (2008).
Greater regional cortical gray matter thickness in obsessive-compulsive disorder. NeuroReport,
19(15), 1551-1555.
Nolte, J (2002). The Human Brain: An Introduction to Its Functional Anatomy (5th ed.). Philadelphia,
PA: Mosby.
Rauch, S. L., Dougherty, D. D., Cosgrove, G. R., Cassem, E. H., Alpert, N. M., Price, B. H., et al.
(2001). Cerebral metabolic correlates as potential predictors of response to anterior
cingulotomy for obsessive compulsive disorder. Biol Psychiatry, 50, 659-667.
Rück, C., Karlsson, A., Steele, J. D., Edman, G., Meyerson, B. A., Ericson, K., et al. (2008).
Capsulotomy for obsessive-compulsive disorder: Long-term follow-up of 25 patients. Arch Gen
Psychiatry, 111(8), 914-922.
Sachdev, P., & Hay, P. (1995). Does neurosurgery for obsessive-compulsive disorder produce
personality change? The Journal of Nervous and Mental Disease, 183(6), 408-413.
Sachdev, P., Trollor, J., Walker, A., Wen, W., Fulham, M. Smith, J. S., et al. (2001). Bilateral
orbitomedial leucotomy for obsessive-compulsive disorder: A single-case study using positron
emission tomography. Australian and New Zealand Journal of Psychiatry, 35, 684-690.
Szeszko, P. R., Ardekani, B. A., Ashtari, M., Malhotra, A. K. Robinson, D. G., Bilder, R. M., et al.
(2005). White matter abnormalities in obsessive-compulsive disorder: A diffusion tensor
imaging study. Arch Gen Psychiatry, 62, 782-789.
14
Joey Mo • 1104542
PSYCI 511 • Dr. Esther Fujiwara
Schruers, K., Koning, K., Luermans, J., Haack, M. J., & Griez, E. (2005). Obsessive-compulsive
disorder: A critical review of therapeutic perspectives. Acta Psychiatr Scand, 111, 261-271.
Swoboda, K. J., & Jenike, M. A. (1995). Frontal abnormalities in a patient with obsessive-compulsive
disorder: The role of structural lesions in obsessive-compulsive behavior. Neurology, 45, 21312134.
Torregrossa, M. M., Quinn, J. J., & Taylor, J. R. (2008). Impulsivity, compulsivity, and habit: The role
of the orbitofrontal cortex revisited. Biol Psychiatry, 63(3), 253-255.
Yoo, S. Y., Jang, J. H., Shin, Y. W., Kim, D. J., Park, H. J., Moon, W. J. et al. (2007). White matter
abnormalities in drug-naïve patients with obsessive-compulsive disorder: A diffusion tensor
study before and after citalopram treatment. Acta Psychiatr Scand, 116, 211-219.
15