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 Different brain areas involved in either idiopathic or acquired Obsessive Compulsive Disorder (OCD) December 2010 Ilse Wielaard Studentnr. 3056953 Neuroscience & Cognition – Cognitive Neuroscience Supervisor AMC : Martijn Figee Supervisor UMCU : Martien Kas Coördinator : Albert Postma Abstract Introduction: Knowledge about Obsessive Compulsive Disorder (OCD) is accumulating through neuro‐imaging research investigating involved brain circuits, most notably the CorticoStriatoThalamoCortical (CSTC) circuit. Somewhat hidden is the fact that over time many case reports have been published on acquired OCD due to neurological lesions. Although these cases may yield important insights into the neuro‐anatomy of OCD, to our knowledge they have never been reviewed. In this article, we will review all published cases of OCD due to acquired brain lesions for a bottom‐up understanding of OCD’s neuro‐anatomy. These findings may lead to a better understanding of brain areas that can be targeted with Deep Brain Stimulation (DBS). Methods: PubMed, PsychInfo, Scholar Google were used to find case reports about acquired OCD, either alone or in combination with other related basal ganglia disorders, like Huntington’s and Parkinson’s disease. This search yielded a total of 31 case reports, dated from 1988 until 2010, which contained 57 cases of acquired OCD. The age‐range was 7‐78 years. Results: In most case reports acquired OCD could be traced back to lesions of the basal ganglia and frontal lobes. Other associated areas were the temporal and parietal lobes. In addition, the occipital lobe, cerebellum and brainstem were involved in some of the cases. The described obsessive‐compulsive symptoms consisted mostly of obsessive doubts and checking, contamination fear and washing, and repetitive mental rituals. Other associated behavioral phenomena were apathy, depression and aggression. Also several OC‐spectrum disorder symptoms like tics and trichotillomania were observed. Conclusion: Lesion studies on a total of 57 patients with OCD following brain injuries confirm involvement of the cortico‐striatal circuit in OCD pathogenesis. However, additional areas seem to be involved, such as the cerebellum, parietal cortex and brainstem. These findings warrant further research into the role of these areas in OCD, particularly their potential role in DBS. Future research should also investigate the validity of the concept of ‘compulsivity’ as this more fully encompasses the obsessive compulsive symptoms found in these case reports. AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 2 Introduction Having the constant need to meticulously perform various complicated rituals in order to prevent terrible things from happening, knowing it is unrealistic but still feeling compelled to do so. This aspect of Obsessive‐
Compulsive Disorder (OCD) shows the debilitating nature of this disorder. OCD is a chronic psychiatric illness in which the person suffers from recurrent obsessions and/or compulsions that cause severe anxiety or distress. The obsessions or compulsions are time consuming and interfere significantly with the person’s normal routine, occupational functioning, usual social activities, or relationships. A person suffering from OCD may have either obsessions or compulsions, or may have both. See box. 1 for a description of the exact criteria of OCD according to the Diagnostic and Statistical Manual of mental disorders (DSM‐IV‐TR, 2000). Obsessions are recurrent and persistent thoughts, impulses or images that are experienced as intrusive and inappropriate, causing marked anxiety or distress. Compulsions are repetitive behaviors or mental acts, often in response to an obsession, that are performed to reduce or prevent anxiety or distress. Initially, people with OCD will try to resist their thoughts and/or compulsions, because they realize their irrationality and excessiveness. The resistance, however, may give rise to anxiety or distress which in return leads to giving in to the thoughts and compulsions, inciting a vicious cycle. As time goes by, the patient may develop a complete network of coercive rituals, performed habitually and automatically, and will therefore be even harder to resist. If left untreated, OCD usually follows a chronic and progressive course. Box 1. The DSM‐IV describes the Obsessive‐Compulsive Disorder as follows: A.
Either obsessions or compulsions: Obsessions as defined by 1), 2), 3) and 4): 1). Recurrent and persistent thoughts, impulses, or images that are experienced at some time during the disturbance, as intrusive and inappropriate and that cause marked anxiety or distress. 2). The thoughts, impulses, or images are not simply excessive worries about real‐life problems. 3). The person attempts to ignore or suppress such thoughts, impulses, or images are a product of his or her own mind (not imposed from without as in thought insertion). Compulsions as defined by 1) and 2): 1). Repetitive behaviors (e.g. hand washing, ordering, checking) or mental acts (e.g. praying, counting, repeating words silently) that the person feels driven to perform in response to an obsession, or according to rules that must be applied rigidly. 2). The behaviors or mental acts are aimed at preventing or reducing distress or preventing some dreaded event or situation; however, these behaviors or mental acts either are not connected in a realistic way with what they are designed to neutralize or prevent, or are clearly excessive. B.
At some point during the course of the disorder, the person has recognized that the obsessions or compulsions are excessive or unreasonable. Note: This does not apply to children. C.
The obsessions or compulsions cause marked distress, are time consuming (take more than 1 hour a day), or significantly interfere with the person’s normal routine, occupational (or academic) functioning, or usual social activities or relationships. AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 3 D.
I another axis I disorder is present, the content of the obsessions or compulsions is not restricted to it (e.g. preoccupation with food in the presence of an eating disorder; hair pulling in the presence of trichotillomania; concern with appearance in the presence of Body Dismorphic Disorder; preoccupation with drugs in the presence of a substance use disorder; preoccupation with having a serious illness in the presence of hypochondriasis; preoccupation with sexual urges or fantasies in the presence of a paraphilia; or guilty ruminations in the presence of major depressive disorder). E.
The disturbance is not due to the direct physiological effects of a substance (e.g. a drug of abuse, a medication) or a general medical condition. Researchers found the prevalence of OCD to be much more common than previously suggested. The lifetime prevalence in the general population is estimated at 2‐3%, whereas some researchers estimated higher prevalence rates for outpatient populations (Zohar, 1999; Sadock & Sadock, 2003). The most recent epidemiological studies have shown a six‐month prevalence rate of about 1% (Bebbington, 1998), to a lifetime prevalence rate of 2‐3% (Hollander & Bezanquen, 1997; Sasson et al., 1997). People with OCD often feel ashamed and are hesitant to seek treatment, which could further raise the true incidence of OCD (Nemiah & Uhde, 1989). Among adults there is an equal sex distribution, but among adolescents it shows that boys are more commonly affected than girls. The age of onset is mostly mid‐to‐late twenties (mean age is about 20 yrs), although men (mean about 19 yrs) have a slightly earlier age of onset than women (mean about 22 yrs). Comorbidity is very high among persons with OCD, especially for major depressive disorder (67%) and social phobia (25%). Other comorbid psychiatric diagnoses include alcohol use disorders, generalized anxiety disorder, specific phobia, panic disorder, eating disorders and personality disorders. Particularly interesting are the high comorbidity rates for disorders within the obsessive‐compulsive spectrum that seem to vary along an impulsivity‐compulsivity continuum. These include Tourette’s disorder and other tic disorders, hypochondriasis, body dismorphic disorder, trichotillomania, eating disorders and other impulse‐related disorders (Samuels & Nestadt, 1997; Angst et al., 1997; Hollander et al., 2007). Richter et al. (2003) found that the OCD population had a 37% greater prevalence of lifetime obsessive‐compulsive spectrum disorder (OCSD), compared to a panic disorder and social phobia‐group. Historical perspectives on OCD Numerous theories about OCD have been developed over the years, some focusing on biological factors, others on behavioral or psychosocial factors. This section offers an overview of the research history and research lines, followed by a discussion on different theories and models. In 1903 Pierre Janet was the first to describe the symptoms of OCD without suggesting these were signs of demonic possessions as was previously thought (Kant et al., 1996). Later on, the psychodynamic model of the development of OCD was introduced by Freud (1959), then called obsessional neurosis. Freud suggested a defensive treat was involved in the face of anxiety‐provoking oedipal wishes (Sadock & Sadock, 2003), regressing to an earlier stage of development. This model contributed to understanding problems with AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 4 treatment compliance (secondary disease gains), interpersonal problems (involvement of the relatives) and personality problems accompanying the axis I disorder, in people with OCD. Another theory considered the symptoms of OCD from the behavioral point of view. According to behavioral and learning theorists, obsessions are conditioned stimuli. In OCD, anxiety becomes a conditioned/learned response to a specific stimulus or set of stimuli (Kant et al., 1996), which were previously neutral objects and thoughts. The compulsions are active avoidance strategies, actions attached to an obsessional thought to reduce or control the anxiety or distress. Gradually, these strategies become learned patterns of compulsive behaviors. Although the behavioral approach gave new insights and ideas for treatment, it left many questions unanswered. Modern research on learning tried to overcome the shortcomings of these earlier behavioral learning theories (Mineka & Zinbarg, 2006). Ethological theories, to continue with, consider compulsive behavior of animals and the development of human OCD to be part of one evolutionary continuum. Animals, for example dogs, also show compulsive actions – rituals (Holden et al., 2010). These so‐called fixed action patterns can be seen as evolutionary survival. This can also be seen in the uniformity of rituals in OCD through the world, where almost all themes of fear have to do with survival (Denys & De Geus, 2007). This evolutionary perspective can explain the universal and compulsive nature of OCD, the implicit character and the meaningless aspect of obsessions and compulsions (Stein et al., 1992). This ethologic perspective, together with a neurologic and genetic perspective, suggests that people with a genetic predisposition have a higher chance to develop OCD under certain circumstances, such as an infection, a neurologic condition or psychological stress (Denys & De Geus, 2007). Under these circumstances obsessive‐compulsive patterns may be functional, becoming dysfunctional over time. However, it seems no longer important to find the original causal factors once the mechanism of OCD has developed, because merely the source does not explain the subsequent development of obsessions and compulsions (Denys & De Geus, 2007). More recently, biological factors are added to the etiology of OCD and are thought to play a rather large role. In the neurobiology of OCD three lines of research can be distinguished. The first line of research concerns genetic involvement in OCD. Available data suggests that there is indeed a significant genetic component (Samuels & Nestadt, 1997; Sadock & Sadock, 2003). However, it is still difficult to distinguish the heritable factors from the behavioral and cultural components. Secondly, a focus on neurotransmitter systems shows that especially serotonin, dopamine and glutamate are involved in the symptom formation of obsessions and compulsions. Hence, drugs tapping into the serotonergic and dopaminergic systems seem to be more effective than other types of drugs. It is however still unclear whether these neurotransmitters are causally involved in OCD or are due to secondary changes following illness onset. Lastly, functional brain‐
imaging data implicate altered function in a neural network involving the Orbital Frontal‐Cortex (OFC), basal ganglia/striatum and thalamus (Insel, 1992; Whiteside et al., 2004; Menzies et al., 2008). Structural abnormalities have also been reported in various structures including the basal ganglia (especially the caudate) and the frontal cortex (Menzies et al., 2008). For example, differences were found in gray matter density in the striatum (Pujol et al., 2004) and orbitofrontal cortex (Kim et al., 2001). Although Aylward et al. (1996) AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 5 concluded in a meta‐analysis that structural differences have not been consistently found in OCD. Together, this led to consideration of an orbitofrontal‐striatal model to mediate such complex behavior as seen in OCD (Cummings, 1993; Graybiel & Rauch, 2000; Stein, 2002; Menzies et al., 2008). Studies investigating OCD pre and post pharmacological and behavioral treatments have shown to reverse brain abnormalities within this network (Baxter et al., 1992). Several theories are developed about the neurobiological mechanisms involved in OCD, which will be described later on. For a good understanding of these theories and the brain areas involved in cases of acquired OCD, the next section will first focus on the neurobiological factors, specifically looking at brain‐
imaging results. Each separate part of the putative brain models will be discussed. Below, the frontal, parietal and temporal association cortices will be considered, together with the basal ganglia and the limbic system. We will describe their anatomic lay‐out, normal function and potential involvement in OCD pathogenesis. Basal ganglia There has been increasing interest in the role of the basal ganglia in normal as well as psychiatric, pathological functioning. The basal ganglia consist of a group of subcortical nuclei in the brain, namely the striatum, globus pallidus, substantia nigra, subthalamic nucleus and the limbic sector of the basal ganglia (figure 1). The last consists of the nucleus accumbens, Ventral Pallidum (VP) and the Ventral Tegmental Area (VTA). The basal ganglia have been considered in a variety of functions, like learning and motor control. Especially the caudate nucleus and the putamen (dorsal striatum) together with the globus pallidus are relevant for motor function. The basal ganglia constitute of a subcortical loop that links most areas of the cerebral cortex with upper motor neurons in the primary motor and premotor areas, and in the brainstem. Activity within this loop is modulated in anticipation of and during movements. In case of a disturbance within this mechanism, the motor systems cannot switch smoothly between commands that initiate a movement and those that terminate it (Purves et al., 2008). Several neurological conditions, like Parkinson’s and Huntington’s disease, are primarily related to disturbances within the basal ganglia. The striatum can be divided into a dorsal and a ventral part. The dorsal part consists of the dorsal caudate nucleus and putamen, which are separated by the internal capsula. The ventral striatum consists of the nucleus accumbens and the ventromedial parts of the nucleus caudatus and the putamen. The striatum is the major input station of the basal ganglia system. It receives input from almost all cortical areas, especially from the frontal and parietal lobes, Figure 1. Basal ganglia but it only innervates other parts of the basal ganglia, like the globus pallidus and substantia AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 6 nigra. These two structures are the main output of the basal ganglia. The efferent cells of the globus pallidus and substiantia nigra are GABAergic, which means that the main output of the basal ganglia is inhibitory. They project to the superior colliculus and via the thalamus to the frontal cortex (Purves et al, 2008). In OCD, the striatum seems to play a very important role since it takes part in habit formation and long‐term reward (Haber et al., 2006), which may both be important in the initiation and continuation of OCD. Through diffuse striatal projections an integrative function may arise as it broadly disseminates general cortical activity, which could also explain the diverse brain areas associated with OCD. Because of its importance the separate parts of the striatum will be considered, namely the caudate nucleus, the putamen and the nucleus accumbens. Suggestions have been made that the caudate nucleus is important to learning and memory, while it processes feedback to understand what is going on around the body. The caudate nucleus, in collaboration with the thalamus, is also considered to play a role in language, particularly switching between different languages. It is suggested that the caudate nucleus is of great importance to OCD and some theoretical ideas exist about the nature of this involvement. For example, Baxter (1990) assumed that the caudate nucleus was responsible for repressing unconscious impulses like aggression, hygiene and sex. Disturbance of the caudate nucleus could lead to less repression through which unwanted thoughts like obsessions could become conscious by entering the prefrontal cortex. Another part of the striatum is the putamen. The putamen is connected with many other structures, which together control various aspects of motor skills, like learning and performing. It is hypothesized that the putamen could also be involved in the selection of movement. In theory, it is suggested that the distinction between the explicit and implicit learning processes plays an important role in OCD: explicit processes are mediated by the dorsolateral prefrontal cortex and the hippocampus, while implicit processes are mediated by the CSTC‐system. In OCD it could be that implicit, unconscious information enters an explicit process through striatal dysfunction causing cognitive intrusions (Deckersback et al., 2002). Additionally, the connection between the striatum and the frontal cortex may play an important role. As was put forward earlier, the output through the striatum is mainly inhibitory, which could disturb the function of the frontal cortex. Aouizerate et al. (2004) suggests that OCD is caused by an imbalance of the ventral and dorsal frontostriatal circuits. Basal ganglia output is almost exclusively through the internal segment of the globus pallidus, together with a part of the substantia nigra (Gazzaniga et al., 2002). Neuro‐imaging studies found smaller globus pallidus volumes in patients with OCD (Szeszko et al., 2004), no model mentions this segment apart. Demirkol et al. (1999) described a case in which an abnormal globus pallidus caused OCD‐symptoms. While the globus pallidus is of importance to the CSTC‐system, the inhibition of the globus pallidus could result in the disinhibition of the ‘gating’ function of the thalamus. This would make the globus pallidus critical in the control of stereotypic behavior in OCD. The substantia nigra is mostly known for its role in Parkinson’s disease through a dramatic decrease of dopamine neurons in this nuclei. The subthalamic nucleus, together with a part of the substantia nigra, is able to modulate the output of the globus pallidus (Gazzaniga et al., 2002). AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 7 Other suggestions were made about the role of the basal ganglia in OCD. For example, Saxena et al. (1998) hypothesized that the ventromedial caudate‐accumbens was responsible for obsession, the dorsolateral part for the compulsions. The limbic system The limbic system consists of several parts, namely the hippocampus, parahippocampal gyrus, fornix, cingulate gyrus, hypothalamus and the amygdala (figure 2). Several parts of the limbic system have been considered to play a role in OCD. These are the amygdala and the cingulate gyrus, which will be discussed below. First, the amygdala is associated with motivationally significant stimuli and is especially known for its role in fear conditioning. Through the ventral striatum, the amygdala has a direct relation with the CSTC‐system, through which Figure 2. Limbic system: (http://brainmind.com/BrainLecture4.html; 23‐08‐2010) it could also take part in the pathogenesis of OCD. LeDoux (2003) developed a model of fear conditioning which explains why behavior that was originally meant to reduce fear becomes compulsive or habitual. Second, the cingulate gyrus seems to be involved in OCD too. The cingulate gyrus is responsible for autonomic functioning like regulating heart rate, blood pressure, but also cognitive and attentional processes. Its input comes from the thalamus and the neocortex, while output is send to the entorhinal cortex. Stimulating the cingulate gyrus in healthy people caused stereotyped, compulsive behavior (Talairach et al., 1998) Thalamus The thalamus functions as a ‘relay’ station to the cortex. A lot of neural information crosses this point before it is send to other parts of the brain. The thalamus has connections with the cortex, basal ganglia, hypothalamus, cerebellum and brain stem. Studies show increased metabolic involvement in OCD of this structure (Perani et al., 1995). Several (PET‐)studies also described changed activity in the thalamus pre and post treatment in OCD (Baxter et al., 1992; Schwartz et al., 1996; Gilbert et al., 2000). Insel (1992) even suggested that the thalamus is involved in the formation of OCD symptoms. Frontal cortex The frontal association cortex is involved in planning and organization. The frontal cortex has a wider repertoire of functions than any other neocortical region (Purves et al., 2008). The frontal cortex integrates complex information from sensory and motor cortices, as well as from the parietal and temporal association cortices. This results in an appreciation of self in relation to the world that allows behaviors to be planned and AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 8 executed normally. Lesions to this region could cause a wide variety of behavioral disturbances, e.g. personality changes. One part of the frontal cortex seems to be particularly involved in OCD, namely the OrbitoFrontal Cortex (OFC). This part of the frontal cortex seems to be important in decision‐making and expectation, sensory integration and representing the affective value of reinforcers (Kringelbach, 2005). Earlier the CSTC‐system was implicated in OCD, Insel (1992) states that a hyperactive OFC causes dysfunction of the CSTC‐system which causes obsessive compulsive symptoms. In addition, Breiter & Rauch (1996) suggest the posteromedial part of the OFC to be responsible for fear and urges as in Gilles de la Tourette. The anterolateral part of the OFC is together with the ventromedial caudate responsible for the obsessions. It has been suggested that certain behavioral changes seen in OCD bear resemblance to behavioral disturbances called frontal lobe syndrome (Donovan & Barry, 1994). The frontal lobe syndrome consists of trauma to the frontal lobe followed by several behavioral characteristics like inhibition problems and personality changes. This can also be seen in OCD patients, for example the fact that patients are unable to bring their stereotyped activities to a halt. This resemblance to the frontal lobe syndrome is especially clear in case reports where lesions caused obsessive compulsive symptoms which are devoid of anxiety (Donovan & Barry, 1994; Laplane et al., 1989). However, the behavioral disturbances in OCD could also be explained by abnormalities in the corticostriatothalamo system, leading to disturbance of the ‘gating’ function of the basal ganglia, followed by overactivity of the frontal cortex (Kant et al.,1996). This could also explain the frontal lobe dysfunction that has often been found in association with OCD . For example, Weilburg et al. (1989) described difficulties inhibiting responses on a go‐no‐go task in a patient with OCD. This task is sensitive to frontal or caudate dysfunction. Difficulties during this task are associated with vulnerability to intrusion, tendency for perseveration, and inhibition problems. In addition, Weilburg and colleagues (1989) described the dense, direct projections from the PFC to the head of the caudate nucleus. They suggested that following this connectivity, lesions in the head of the caudate nucleus could produce the same behavioral deficits following prefrontal lesions. Deficits associated with frontostriatal dysfunction parallels many of the abnormal behaviors seen in patients with OCD. However, other aspects of a frontal lobe deficit, like senseless repetitive, stereotyped activities, fearless and egosyntone features, do not match with characteristics of OCD. It still indicates that behavioral and neuropsychological parallels exist between frontal lobe deficits and OCD. Other parts of the brain Other parts of the brain that could be considered of importance in OCD are the parietal lobe, the temporal lobe and the cerebellum. The parietal association cortex is involved in attention and spatial orientation. Damage to this area could cause contralateral spatial neglect or apraxia (Purves et al, 2008). A study of Kitamura et al. (2006) showed white matter abnormalities in the parietal cortex in patients with obsessive‐
compulsive disorder. The temporal association cortex is involved in the identification and recognition of complex stimuli, like faces, that are attended to (Purves et al., 2008). Damage to this area causes for example agnosia. Some AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 9 research articles mention temporal lobe abnormalities in OCD (Hugo et al., 1999; Jenike et al., 1984; Ames et al., 1994; Berthier et al., 1996). The cerebellum is mostly known for its role in motor control. Recently, it is also considered to regulate attention, language and emotions. More research is needed to clarify its specific role in cognition. Although a considerate amount of OCD studies suggest structural differences and changed activity in the cerebellum (Kim et al., 2001; Pujol et al., 2004; van den Heuvel et al., 2009), research has found no conclusive involvement of this structure. The brain is known to work in circuits and networks connecting several brain areas. Consequently, one could assume that in such complex behaviors as seen in OCD parts of the brain have to work together. This implies that certain brain circuits are involved in the etiology of OCD (e.g. Saxena et al., 1998). In theory it is possible that different lesions could lead to the same behavioral change, as long as the net effect on the whole brain circuit is the same (also Weilburg et al., 1989). In short, considering connections between brain areas involved in OCD is a necessity in comprehending OCD. One brain circuit that has been proposed is the CorticoStriatoThalamoCortical (CSTC)‐system (e.g. Saxena et al., 1998; Graybiel & Rauch, 2000; Menzies et al., 2008). Although studies agree on the existence of differences in the CSTC‐system, research still does not agree on the nature of the abnormalities in this system (Denys & De Geus, 2007). And although the CSTC‐
circuit explains the obsessional intrusions and repetitions, it does not explain the affective component, which is fear. This lack of explanation of the CSTC‐model makes it worthwhile to consider the amygdala in this review in addition to the other brain regions. Below, the connections between brain areas involved in OCD will be considered, in particular investigating the usefulness of the CSTC‐system, which will be described first. The CSTC‐system includes the cortex, striatum, globus pallidus (basal ganglia) and the thalamus, which were discussed previously. It also contains several parallel networks, each with its own function. Some involve implicit learning and are responsible for acquiring a habit or for a ritual, or for performing routines. Others involve explicit learning and process conscious information using memory functions. The CSTC‐system consists of a direct, excitatory circuit and an indirect, inhibitory circuit. The direct circuit is responsible for activation and upkeep of behavior, while the indirect circuit is responsible for inhibition and changing of behavior. Both systems are controlled by dopamine, the direct circuit by D1 receptors and the indirect circuit by activation of the D2‐receptors. Considering the connections within the system and their role in OCD, different abnormalities were found. For example, Kant et al. (1996) suggested that abnormalities in the CSTC‐system led to disturbance of the ‘gating’ function of the basal ganglia and overactivity of the frontal cortex. This could also explain the frontal lobe dysfunction that has been found in OCD (Weilburg et al., 1989; Donovan & Barry, 1994;Laplane et al., 1989). Another possible explanation is that obsessions are the result of a positive feedback loop between the thalamus and the prefrontal cortex, while the compulsions on the other hand are a result of a striatal dysfunction (Rauch & Jenike, 1993). Modell et al. (1989) mentioned hyperactivity of the caudate nucleus as a cause of excitation of the thalamus. Baxter (1990) assumes hyperactivity of the caudate nucleus is caused by AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 10 insufficient compensating striatal dysfunction, which causes insufficient inhibition of the thalamus. Following Gamazo‐Garrán et al. (2002) and Hugo et al. (1999), the neuro‐anatomical model associated with OCD should involve hyperactivation of orbitofrontal, limbic and basal ganglia (mainly the caudate nucleus) circuits. Donovan & Barry (1994) support this by mentioning that obsessive compulsive symptoms have been reported in association with injury to the frontal lobes and basal ganglia. Accumulating neuro‐imaging data implicate dysregulation of pathways linking the OFC and the caudate nucleus. For example Baxter et al. (1987) describe increased activation in the caudate nuclei and the left OFC in 14 patients with OCD using PET scan. A study of Hugo et al. (1999) investigated patients with acquired OCD, who demonstrated decreased blood flow in the temporal lobes as well as perfusion abnormalities in the frontal lobes. These abnormalities may be seen in other brain regions. It is still unclear whether these abnormalities reflect primary neurological lesions or secondary changes to compensate for the loss of tissue. It could well be that increased frontal blood flow in OCD reflects a compensatory mechanism. Hugo et al. (1999) further argue several possibilities. It could be that frontal hyperactivity is the primary deficit, which could lead to disinhibition of the thalamo‐cortical limb of the frontal‐subcortical circuit. This means that the patient gets overwhelmed by internally generated cues (Insel, 1992). On the other hand, frontal hypo‐activity is also possible. In this case the basal ganglia is the site of primary deficit, where areas of frontal hyperactivity are associated with resistance to symptoms or secondary compensation. Parent & Hazrati (1995) and Mordecai et al. (2000) propose that certain neural processing ‘loops’ could explain the way basal ganglia structures might be implicated in the modification of thought. It seems that the cortex, striatum, globus pallidus (pallidum) are involved in these loops. Furthermore, it has been hypothesized that the ventral striatum in interaction with limbic structures contribute to affective regulation (Miguel et al., 1997). This could also explain the affective changes noticed in several case reports. The aforementioned brain areas are involved in other disorders as well, like Gilles de la Tourette, Parkinson’s and Huntington’s disease. Case reports have mentioned combined existence. For example Daniele et al. (1997) describe patients with Parkinson’s disease and OCD, and later on dementia. It could be argued that the brain structures/circuits involved in these neurological diseases are also affected in OCD (e.g. Patzold & Brüne, 2002). Mordecai et al. (2000) mentions that the basal ganglia are involved in all sorts of disorders like OCD, psychosis, schizophrenia, Sydenham chorea, Tourette’s disorder, postencephalic parkinsonism and Huntington’s disease (also Miguel, 1997; Swedo, 1998). For example, in Parkinson’s disease dopaminergic neurons in the substantia nigra dramatically decrease and in Huntington’s there is a degeneration of neurons in the striatum. Furthermore, Demirkol et al. (1999) suggested involvement of the same CSTC circuit in Tourette Syndrome (TS) and Attention Deficit Hyperactivity Disorder (ADHD), while this circuit is of central importance in normal control of motor, cognitive and affective functioning. It is important to keep in mind that the mechanisms of OCD could overlap with other disorders. AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 11 Neurobiological perspectives on OCD In line with these studies using brain‐imaging methods, several theories on how these brain activities changed and caused such complex obsessive‐compulsive behavior emerged. In OCD several mechanisms act on different moments in time, which makes OCD a changeable disorder with more than one layer. This also stresses the importance of theoretical models that explain these different aspects, for example the cognitive and affective disturbances. Accordingly, OCD is seen from three different views in modern theories: namely from a cognitive, an affective and a behavioral view. The cognitive model of OCD stresses the lack of cognitive inhibition by a dysfunction of the CorticoStriatoThalamoCortical (CSTC)‐system. Cognitive disinhibition means that unconscious intolerable thoughts become unwillingly conscious. These intrusions can also be seen in the normal population, but in a lesser amount, less intense and less disturbing. This way obsessions and compulsions are abnormal, unadjusted thoughts of actions, uncontrollable by the patients. Obsessions can then be explained by difficulties in changing (diverse) attention or in stopping thoughts. These inhibition problems may be related to hyperactivity of the orbitofrontal cortex, the anterior cingulated cortex and the caudate nucleus, which represent the lateral orbitofrontal loop of the CSTC‐system (Chamberlain et al., 2005). Hyperactivity of the CSTC‐system may be caused by increased dopaminergic activity, due to higher density of the dopamine‐D1‐receptors (Olver et al., 2009). Second, OCD is characterized by an affective aspect, namely fear. This can be explained by disturbance of fear conditioning, which is associated with the amygdala (LeDoux, 2003). LeDoux mentions in his article that damage to the amygdala leads to a disruption of the acquisition and expression of fear. The process of fear conditioning increases the amygdala activity. Normally, the prefrontal cortex sends feedback signals to the amygdala to reduce the expression of fear, by adding information. Studies show that cortical inhibition fails in cases of increased dopaminergic activity, which means that the fear conditioning in the amygdala is not reduced (Rosenkranz & Grace, 2002). In OCD that normal cortical inhibition of the amygdala seems to be disturbed through which the fear, induced by the amygdala, is longer and more intrusive. Third, behavioral addiction seems to play a role in OCD. This means that despite negative consequences of acts, a person suffering from OCD might still feel obliged to act on those obsessions and compulsions. Some characteristics of OCD, e.g. the development of rituals, the compulsitivity, and the loss of control, , indeed show a striking resemblance to an addiction. The uncertainty (what if..) and the reward (feeling relieved), in case of addiction, coincide with increased dopaminergic activity, especially in the nucleus accumbens (Fiorillo et al., 2003). One could argue that the uncertainty and the reward of obsessions and compulsions also coincides with increased dopaminergic activity, which induces the dependence (addiction). Current research Present research is focusing on the use of Deep Brain Stimulation (DBS) as a treatment for OCD. This is one of the neurosurgical interventions that can be used in case of a very disabling and treatment refractory form of OCD. In a review, Gabriëls et al. (2007) described how different centers over the world have started prospective research with DBS. Each center has been focusing on different brain regions, applied different AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 12 protocols and used different types of electrodes. For instance, some studies implanted the electrode in the capsula interna, others implanted it in the nucleus accumbens (Denys et al., 2010). Future investigations need to show reliable, replicable results, which would make this intervention a promising treatment for OCD. One way to achieve reliable information on OCD is by acquiring bottom‐up information, which can be collected from case reports of patients with acquired instead of idiopathic OCD. These case reports may provide us with unique information on neuroanatomical substrates of OCD that can be targeted with DBS. Objective of this review Several neurobiological abnormalities found in imaging research have been described. As Mordecai et al. (2000) mentioned, the behavioral presentation of a disorder is dependent upon the location of the tumor or brain lesion. This means that studying case reports of brain lesions associated with OCD could lead to an increased understanding of the neuronal circuitry underlying these behaviors. Swoboda & Jenike (1995) also suggested that patients with specific brain lesions, which are associated with the onset of OCD, could provide valuable insights into the neurobiology of this disorder. As we have seen, experimental research has had great impact on models and theories that tried to explain complex psychiatric behavior as can be seen in OCD. These top‐down approaches have provided a more thorough understanding of this disorder. However, case reports of acquired OCD may provide a bottom‐up approach allowing for investigations of obsessive‐
compulsive symptoms that have been directly caused by specific brain lesions. Throughout the years many case reports have been published of patients who develop OCD after acquired brain lesions, but these have never been reviewed together. These case reports describe symptoms that have striking similarities with symptoms observed in idiopathic OCD, supporting the hypothesis that specific brain areas mediate this disorder (Hugo et al., 1999). AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 13 Methods Published studies of case reports with acquired OCD were identified through searches of electronic databases (e.g. PsycINFO, PubMed) and reference lists of publications. We searched for: obsessive‐compulsive disorder (OCD), obsessive‐compulsive behaviour (OCB), obsession, compulsion, stereotyped activities, lesion, CVA, hemorrhage, tumour, infarction, stroke, disease, Parkinson’s, Huntington’s, Wilson’s, Tourette’s, Sydenham chorea, basal ganglia, lentincular (nuclei), striatum, nucleus accumbens, globus pallidus, frontal lobe. These words were entered in different combinations in the electronic databases. All studies that contained cases of patients with acquired OCD due to a neurological lesion, a disease that affected brain sites or closed head injuries were included. We only included case reports that also reported neuro‐imaging data, either PET, SPECT or (f)MRI. This pursuit yielded an initial sample of 34 articles that reported a total of 61 cases, published between 1988 and 2010. From this sample, we excluded 2 articles because of the lack of individual information (Alegret et al., 2001; Giroud et al., 1997). Additionally, one study was excluded for methodological reasons, as the study did not provide neuro‐imaging information (McKeon et al., 1984). In particular, two articles were included while the obsessive compulsive symptoms in patients improved or disappeared after brain injury (Fujii et al., 2005; Yaryura‐Tobias & Neziroglu, 2003). Thus, in total 31 case reports (articles) were used, which contained 57 cases of acquired OCD. The age‐
range of the patients was 7 till 78 yrs. These studies were used to compare the brain areas involved in acquired versus idiopathic OCD. AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 14 Results A sample of case reports of patients with acquired OCD was collected to create an overview of different brain areas that could cause obsessive‐compulsive symptoms. The results of these case reports will be discussed on the basis of the involved brain areas. Each separate case that has been studied in the reviewed case‐reports, is briefly described in accompanying tables. Basal ganglia Involvement of the basal ganglia was the most often described finding in case reports on acquired OCD (table 1). Twenty‐four case reports (36 patients) mentioned development of OCD following infarcts or tumors in the basal ganglia. Seven cases were found in which the basal ganglia was exclusively involved. For example, Chacko and colleagues (2000) presented three cases where OCD symptoms were caused by bilateral basal ganglia infarcts and one case that was caused by unilateral, right basal ganglia infarct. Two case reports described acute remission of OCD‐symptoms after a hemorrhage of the left basal ganglia (Yaryura‐Tobias & Neziroglu, 2003; Fujii et al., 2005). The striatum was involved in thirteen case reports (27 patients), of which five exclusively mentioned involvement of this area. Involvement of the caudate nucleus was reported in eleven case studies (16 cases), the putamen was involved in seven case reports (11 cases) and the internal capsula was mentioned in two case reports (two cases). For example, Thobois et al. (2004) presented a 24‐
year‐old male who experienced compulsive behavior with intermittent aggressiveness after removal of a hematoma located at the head of the left caudate nucleus. These compulsions were described as egodystone, but not associated with anxiety. Weilburg et al. (1989) wrote about a 24 yr old student who exhibited contamination fear obsessions and hand‐washing compulsions, with co‐morbid depression, after unilateral left‐sided abnormalities in the head of the caudate nucleus and putamen. Tonkonogy & Barreira (1989) described a case of OCD due to bilateral caudate atrophy, in which the caudate lesion was not accompanied by structural changes in other striatal structures as in cases of Laplane et al. (1981) and Weilburg et al. (1989). This points to the probable crucial role of the caudate nucleus in the development of OCD. The globus pallidus was affected in four case reports (ten cases). Demirkol et al. (1999) for example, described a 17‐year‐old male with bilateral globus pallidus lesions, who subsequently developed washing and orderliness compulsions accompanied by Tourette’s syndrome (simple and complex motor and vocal tics), attention deficit hyperactivity disorder (ADHD), stuttering and gait disturbance. Interestingly, in a 34‐year old male patient, globus pallidus lesions were related to development of trichotillomania, which is regarded as a disorder within the same spectrum as OCD (Escalone et al., 1997). Two case reports (Daniele et al., 1997; Hugo et al., 1999) mentioned involvement of the substantia nigra in OCD symptoms. Limbic system Because of its importance in anxiety, lesions in the limbic system might be expected in case reports on acquired OCD (table 2). However, only two case‐reports, consisting of three patients, described involvement AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 15 of lesions in the cingulate gyrus. One case report (two cases) found involvement of the hypothalamus and fornix. Associated effects were intrusive checking thoughts and compulsions. Changed activity did not exclusively involve nuclei of the limbic system; other brain areas were involved in all of the cases. Thalamus Involvement of the thalamus was found in four case reports (five patients; table 4). The behavioral effects consisted of compulsive checking, compulsively pinching people, and tapping doors and tables. Frequent mood changes were also observed. Frontal cortex Sixteen case reports (25 cases) mentioned OCD that was related to frontal brain lesions (table 5). Seven case reports mentioned the frontal cortex exclusively as a cause for the obsessive‐compulsive symptoms (e.g. John et al., 1997; Swoboda & Jenike, 1995; Ward, 1988). Donovan & Barry (1994) presented a case of a 22‐year‐old male with infarction of the right frontal lobe and a left subfrontal contusion who thereafter experienced compulsive rhythmic activities and counting symptoms devoid of anxiety. The constellation of behavioral symptoms was associated with features of a frontal lobe syndrome. Three reports specifically described the OFC to be involved (Kant et al., 1996; Kim & Lee, 2002; Simpson & Baldwin, 1995). The behavioral symptoms mostly seen after frontal lobe lesions were contamination fears with washing compulsions and needing to know obsessions with compulsive checking. Parietal lobe The parietal lobe was found to be involved in eight cases (table 6). Two case reports described cases in which the parietal lobe exclusively caused the obsessive‐compulsive symptoms (Paradis et al., 1992; Simpson & Baldwin, 1995). Described behavioral consequences were contamination fears, washing rituals, need for symmetry and checking rituals. Neuropsychological deficits were also mentioned, like impaired planning, spatial processing and flexibility. Temporal lobe The temporal lobe was found to be involved in five case reports, consisting of 11 cases, never exclusively causing the obsessive‐compulsive symptoms (table 7). Associated behavioral effects were obsessive doubt, checking, counting, washing rituals and repetitive mental rituals. Depressive symptoms were also described, as well as aggressive thoughts and apathy. One patient also suffered from memory impairment, together with personality changes. AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 16 Occipital lobe Two case reports (five cases) mentioned the occipital lobe to be involved (table 8). None of these reports mentioned solely the occipital lobe to take part in the complex behavior. Among the behavioral effects were obsessive counting, repetitive mental rituals and aggressive thoughts. Cerebellum The cerebellum was mentioned in two case reports (table 9), in one case probably exclusively causing the OCD (Gonzalez et al., 1998). The obsessive‐compulsive symptoms consisted of checking and washing. Brainstem Four case reports (four cases) wrote about involvement of the brainstem (table 10). The obsessive‐compulsive symptoms reported in these cases were contamination fear, checking and washing. Mood lability, aggression, delusions and suicidal ideation were also part of the behavioral consequences. AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 17 Table 1. Case reports on involvement of the basal ganglia Brain area Nr. Article Cases M/F Main site of lesion Behavioral symptoms Basal ganglia ‐ unspecified ‘Needing to know’ obsessions and resulting checking rituals, phobic avoidance OCB**: spouse infidelity OCB: counting/hair combing + depressed mood OCB: fear of harming + psychiatric symptoms OCB: checking/ordering + depression 2 yr history of OCD: checking, repeating behaviors, need for symmetry and excessive exercising. Intrusive checking thoughts and compulsions ‘empty mind’, no depression, stereotyped activities (OCD), angry, not apparently anxious. OCD ‐ mental stereotyped activities (counting), apparent lack of spontaneous activity. Passivity, lack of initiative, no OCD. Inactivity and lack of volition, no OCD. Extremely inert; sad and pessimistic, subject to OC‐
behavior and lack of inhibition. No initiative, only when asked; polymorphic compulsive behavior (checking, counting, rituals); angry, not apparently anxious; major memory difficulties. Psychopathic personality, impulsivity, OCD (counting, vocal repetitions). No OCD. 1 Carmin et al., 2002 M (78) Two infarcts basal ganglia 4 Chacko et al., 2000* F(76) F(61) F(77) F(70) 1 Giedd et al., 1996* M(12) 1 Hugo et al., 1999 Laplane et al., 1989 M(41) Bilateral basal ganglia infarcts Bilateral basal ganglia infarcts Right basal ganglia infarction Bilateral basal ganglia calcification Reduced basal ganglia size: size reduction of caudate, putamen and globus pallidus Right frontal haematoma 1 Mittal et al., 2010 M(17) 1 Mordecai et al., 2000 M(13) 1 Scicutella, 2000 M(72) 1 Simpson et al., 1995 M(71) 8 M(53) M(23) M(59) M(52) F(27) M(?) F(31) F(22) AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 Bilateral lesions lentiform nucleus, small lesions caudate and putamen. Bilateral globus pallidus, internal part of the lentiform nucleus. Bilateral calcified lesions basal ganglia, mostly globus pallidus. Bilateral lesions involving parts of the putamen, lateral pallidal segment and head of the caudate nucleus. Bilateral lesions within the lentiform nuclei (almost whole globus pallidus). Bilateral lesions globus pallidus. Bilateral lesion of the lentiform nuclei, anterior part of the globus pallidus. Bilateral internal segment of the globus pallidus. Small left‐sided basal ganglia stroke; tumor in the dorsal midbrain/pineal cistern; hydrocephalus Bilateral lesions basal ganglia + abnormalities in the internal capsula, frontal lobes, peduncles and pons Paraventricular white matter changes, possible basal ganglia lesion Right inferior parietal infarct OCD (checking), stereotypic motor activities + depressions, psychotic symptoms OCD‐symptoms (need to say, repetition), mood lability, aggression, suicidal ideation, delusions and left hemiparesis Personality changes, anxiety & agitation, contamination fears, washing rituals (FTD & HD) OCD symptoms: needing to know and remember 18 1 Ward, 1988 F(62) 1 Yaryura‐Tobias et al.,2003* M(33) Hematoma of the left caudate nucleus, and anterior part of the putamen Unilateral left‐sided abnormalities in the head of the caudate nucleus and putamen Total 21 Striatum Total 1 Thobois et al., 2004* M(24) 1 Weilburg et al., 1989* 2 Caudate Nucleus 1 Chacko et al., 2000 F (77) 1 Gamazo‐Garran et al., 2002 M(16) 1 4 1 Giedd et al., 1996 Laplane et al., 1989 Patzold et al., 2002* M(12) 2 Peterson et al., 1996 F(8) M(7) 1 Swoboda, 1995 M(70) 1 Tonkonogy et al., 1989 F(36) F(42) AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 Lower activity in right basal ganglia and temporal areas; more activity right OFC Lacunar infarcts in the right superior cerebellar peduncle and left basal ganglia Left basal ganglia hemorrhage (left putamen) Ischaemic changes head of the right caudate, right lateral frontal convexity and the left lateral parietal convexity Tumor affecting caudate nuclei See part: basal ganglia unspecified See part: basal ganglia unspecified Bilateral caudate atrophy Resection of a tumor: injury involving the fornices bilaterally, 3rd ventricle, left hypothalamus, genu of left internal capsule, left caudate nucleus head, right cingulated gyrus, mid‐body corpus callosum. Left parietal tumor involving the corpus callosum, left cingulate gyrus, fornix, left caudate nucleus Infarct in the posterior right frontal region + extensions to deep subcortical white matter Atrophy of the caudate head and frontal lobe bilaterally Urge to shake her right arm OCD disappeared due to hemorrhage – devoid of anxiety and depression, certain degree of apathy and indifference to his OCD Removal of the hematoma caused OCD (compulsive 10 letter sentences), no anxiety Compulsion (hand‐washing), obsession (being ‘not clean’), dizziness and postural changes, episodes of depression OCB: dental disease + depressed mood OCD, checking obsession and compulsions pinching people, tapping doors and tables + frequent mood changes Ten yrs of Huntington’s disease Obsessive ideation, persistent thoughts of killing her neighbor, no additional compulsive symptoms Already developed tics – vocal, facial etc. After surgery, numerous repetitive stereotypies and compulsions. Obsessive preoccupation with tactile stimuli. Motor tics; Did not meet formal OCD criteria, but kept everything extremely neat Acute onset of OCD (needing to know) symptoms Compulsive hand‐washing, thoughts of cleanliness and contamination fear, excessive washing. Limited insight and 19 2 Weiss & Jenike, 2000* F(70) M(75) 1 Williams et al., 1988* F(48) 1 Daniele et al., 1997 F(63) Left putamen + bilateral size reduction substantia nigra 1 Fujii, 2005* M(58) 1 Giedd et al., 1996 Laplane et al., 1989 Yaryura‐Tobias et al.,2003* M(12) Left putaminal hemorrhage + probably involvement of lateral segment of the globus pallidus and tail of the caudate nucleus and limb of internal capsule See part: basal ganglia unspecified See part: basal ganglia unspecified Left basal ganglia hemorrhage (left putamen) Total 16 Putamen Total 5 1 9 M(33) OCD disappeared due to hemorrhage – devoid of anxiety and depression, certain degree of apathy and indifference to his OCD Hugo et al., 1999 M(32) Peterson et al., 1996 F(8) Senseless and intrusive aggressive thoughts + repetitive mental rituals Already developed tics – vocal, facial etc. After surgery, numerous repetitive stereotypies and compulsions Obsessive preoccupation with tactile stimuli Generalized atrophy + lacunar infarct right internal capsula Resection of a tumor: injury involving the fornices bilaterally, 3rd ventricle, left hypothalamus, genu of left internal capsule, left caudate nucleus head, right cingulated gyrus, mid‐body corpus callosum Demirkol et al., 1999* Escalone et al., 1997* M(17) Bilateral globus pallidus lesions 3 yrs rituals: orderliness & washing M(34) Bilateral globus pallidus infarction M(12) 7 Giedd et al., 1996 Laplane et al., 1989 10 See part: basal ganglia unspecified See part: basal ganglia unspecified OCD: obsessions: thoughts of harming, sexual fantasies, contamination fear; compulsions: checking, washing and counting. + blunted affect + trichotillomania symptoms 1 1 1 AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 Obsessive thoughts (fear of what could happen to her children), later compulsions started (verbal iterations, coprolalia) + aggressive outbursts Started having OCD symptoms at 43 yrs, improvement after hemorrhage Internal 1 capsula 1 Total 2 Globus Pallidus Total Abnormalities head of the left caudate nucleus + diffuse, mild cortical atrophy Bilateral infarct caudate nucleus Cavitation bilateral caudate nuclei, probably the putamen agitated depression Æ OCD symptoms with increased atrophy Abnormalities head of the left caudate nucleus + diffuse, mild cortical atrophy OCD – infection & contamination worries, guilt Simulating typing exercise, depressive symptoms, likely lower intellectual functioning 20 Substantia Nigra 1 Daniele et al., 1997 F(63) Left putamen + bilateral size reduction substantia nigra Obsessive thoughts (fear of what could happen to her children), later compulsions started (verbal iterations, coprolalia) + aggressive outbursts * means exclusively involved ** OCB= Obsessive‐compulsive behaviour Table 2. Case reports on involvement of the thalamus Nr. Cases 1 Article Daniele et al., 1997 M/F F(63) Main site of lesion Left putamen + bilateral size reduction substantia nigra 1 Gamazo‐Garran et al., 2002 M(16) Tumor affecting caudate nuclei 2 Hugo et al., 1999 1 Peterson et al., 1996 5 in total M(41) Right frontal haematoma. M(59) Bilateral anterior temporal and anterior frontal lobe atrophy. M(12) Hydrocephalus through a right tectal lesion involving the periaqueductal gray, right red nucleus, right thalamus, right subthalamic nuclei. Behavioral symptoms Obsessive thoughts (fear of what could happen to her children), later compulsions started (verbal iterations, coprolalia) + aggressive outbursts OCD, checking obsession and compulsions pinching people, tapping doors and tables + frequent mood changes Intrusive checking thoughts and compulsions. Obsessive doubt and compulsive checking + symptoms of depression. OCD (checking, ordering, list making and ritualized behaviours) ADHD; motor and vocal tics; nightmares and depression. Table 3. Case reports on involvement of the pineal gland Nr. Cases 1 Article Mittal et al., 2010 M/F M(17) Main site of lesion Small left‐sided basal ganglia stroke; tumor in the dorsal midbrain/pineal cistern; hydrocephalus Behavioral symptoms OCD (checking), stereotypic motor activities + depressions, psychotic symptoms AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 21 Table 4. Case reports on involvement of the limbic system Brain lesion Nr. Cases Cingulate gyrus 1 2 Total 3 Article M/F Main site of lesion Behavioral symptoms Hugo et al., 1999 Peterson et al., 1996 M(41) Right frontal haematoma F(8) M(7) Intrusive checking thoughts and compulsions Already developed tics – vocal, facial etc. After surgery, numerous repetitive stereotypies and compulsions. Obsessive preoccupation with tactile stimuli. Motor tics; Did not meet formal OCD criteria, but kept everything extremely neat Resection of a tumor: injury involving the fornices rd
bilaterally, 3 ventricle, left hypothalamus, genu of left internal capsule, left caudate nucleus head, right cingulated gyrus, mid‐body corpus callosum. Left parietal tumor involving the corpus callosum, left cingulate gyrus, fornix, left caudate nucleus Fornix 2 Peterson et al., 1996 (see cingulate gyrus case) Hypothalamus 1 Peterson et al., 1996 (see cingulate gyrus case) Table 5. Case reports on involvement of the frontal lobe Brain area Nr. Cases Article M/F Main site of lesion Behavioral symptoms Unspecified 1 Chacko et al., 2000 F(77) Obsessive‐compulsive behavior (OCB) (dental disease)+ depressed mood 1 Daniele et al., 1997 F(63) Ischaemic changes head of the right caudate, right lateral frontal convexity and the left lateral parietal convexity Left putamen + bilateral size reduction substantia nigra 1 Donovan & Barry, 1994* M(22) Bilateral frontal lobe injury 1 Gamazo‐
Garran et al., 2002 Hugo et al., 1999 M(16) Tumor affecting caudate nuclei M(41) M(59) M(32) F(46) M(41) Right frontal haematoma. Bilateral anterior temporal and anterior frontal lobe atrophy. Generalized atrophy + lacunar infarct right internal capsula. Aneurysm left internal carotid artery Æ SPECT changes. Right anterior‐inferior temporal lobe spongiosis. 6 AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 Obsessive thoughts (fear of what could happen to her children), later compulsions started (verbal iterations, coprolalia) + aggressive outbursts Compulsive symptoms (rhythmic activities, counting, need to read), devoid of anxiety, not associated with obsessions but egodystone + features of frontal lobe syndrome OCD, checking obsession and compulsions pinching people, tapping doors and tables + frequent mood changes Intrusive checking thoughts and compulsions. Obsessive doubt and compulsive checking + symptoms of depression. Senseless and intrusive aggressive thoughts + repetitive mental rituals. Number obsessions, compulsions with counting, intrusive thoughts about other aneurysms + MCI. Personality changes, increased apathy & withdrawal, memory impairment, senseless & intrusive thoughts about possible harm + 22 1 1 John et al., 1997* Mahendran, 2000 F(29) Reduced perfusion temporal, frontal and occipital lobes. M(53) Left frontal tumor M(37) Infarct involving the left frontal, temporal and parietal lobes – dilatation of frontal part of left lateral ventricle Bilateral lesions basal ganglia + abnormalities in the internal capsula, frontal lobes, peduncles and pons Damage to the right frontal parietal area, removal tumor of the right parietal vertex, involving the superior sagittal sinus Infarct in the posterior right frontal region + extensions to deep subcortical white matter Atrophy of the caudate head and frontal lobe bilaterally 1 Mordecai et al., 2000 M(13) 1 Paradis et al., 1992 F(36) 1 Swoboda, 1995* M(70) 1 Tonkonogy et al., 1989 F(36) 2 Ward, 1988* F(59) M(43) Frontoparietal tumor Left frontal mass 2 Weiss et al., 2000* F(56) M(70) 20 Abnormalities bilateral frontal periventricular white matter, + in the central pons. Infarct posterior right frontal lobe, extension to deep subcortical white matter 4 Kant et al., 1996* M(43) M(26) M(16) F(45) Closed head injury Closed head injury Closed head injury; right frontal fracture Closed head injury 1 Kim et al., 2002* Simpson et al., 1995 M(66) Infarct left OFC M(71) Right inferior parietal infarct Lower activity in right basal ganglia and temporal areas; more activity right OFC Total OFC 1 Total 6 symptoms of depression. Personality changes, apathy, little/no insight, intrusive musical tune played in her mind. Acute onset of anxiety and obsessional symptoms with verbal utterances. Compulsive symptoms & rituals, washing and bathing Æ only compulsions OCD‐symptoms (need to say, repetition), mood lability, aggression, suicidal ideation, delusions and left hemiparesis OCD after removal tumor, contamination fears, washing rituals, need for symmetry and checking rituals. Acute onset of OCD (needing to know) symptoms Compulsive hand‐washing, thoughts of cleanliness and contamination fear, excessive washing. Limited insight and agitated depression Æ OCD symptoms with increased atrophy Urge to walk to the left Urge to shake his right arm + sometimes shout OCD – contamination fear OCD – ‘needing to know’ obsessions and compulsions OCD: sexual and aggressive thoughts, fear of acting out. Mild depression, GAD. Personality changes, checking & counting rituals, mild GAD and depression. Counting & checking rituals. Checking & counting, anxiety, cognitive deficits + major depression (paranoia). Obsessions ‘something wrong’ would happen and compulsive checking rituals OCD symptoms: needing to know and remember * means exclusively involved AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 23 Table 6. Case reports on involvement of the parietal lobe Nr. Cases 1 1 1 1 1 1 1 1 8 in total Article Chacko et al., 2000 M/F F(77) Main site of lesion Behavioral symptoms Ischaemic changes head of the right OCB: dental disease + depressed caudate, right lateral frontal convexity mood and the left lateral parietal convexity Hugo et al., 1999 M(59) Bilateral anterior temporal and anterior Obsessive doubt and compulsive frontal lobe atrophy checking + symptoms of depression John et al, 1997 M(53) Left frontal tumor Acute onset of anxiety and obsessional symptoms with verbal utterances. Mahendran, 2000 M(37) Infarct involving the left frontal, Compulsive symptoms & rituals, temporal and parietal lobes – dilatation washing and bathing Æ only of frontal part of left lateral ventricle compulsions Paradis et al., 1992* F(36) Damage to the right frontal parietal OCD after removal tumor, area, removal tumor of the right contamination fears, washing parietal vertex, involving the superior rituals, need for symmetry and sagittal sinus checking rituals. Peterson et al., 1996 M(7) Left parietal tumor involving the corpus Motor tics; callosum, left cingulate gyrus, fornix, Did not meet formal OCD criteria, left caudate nucleus but kept everything extremely neat Simpson et al., 1995* M(71) Right inferior parietal infarct OCD symptoms: needing to know Lower activity in right basal ganglia and and remember temporal areas; more activity right OFC Ward, 1988 F(59) Frontoparietal tumor Urge to walk to the left * means exclusively involved Table 7. Case reports on involvement of the temporal lobe Nr. Cases 1 Article Gamazo‐Garran et al., 2002 M/F Main site of lesion M(16) Tumor affecting caudate nuclei 5 Hugo et al., 1999 Mahendran, 2000 M(37) 1 Simpson et al., 1995 M(71) 1 9 in total Ward, 1988 Infarct involving the left frontal, temporal and parietal lobes – dilatation of frontal part of left lateral ventricle Right inferior parietal infarct Lower activity in right basal ganglia and temporal areas; more activity right OFC 1 Behavioral symptoms OCD, checking obsession and compulsions pinching people, tapping doors and tables + frequent mood changes. Compulsive symptoms & rituals, washing and bathing Æ only compulsions OCD symptoms: needing to know and remember AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 24 Table 8. Case reports on involvement of the occipital lobe Nr. Cases 1 Article Gamazo‐Garran et al., 2002 M/F M(16) Main site of lesion Tumor affecting caudate nuclei 4 Hugo et al., 1999 M(32) F(46) M(41) F(29) Generalized atrophy + lacunar infarct right internal capsula. Aneurysm left internal carotid artery Æ SPECT changes. Right anterior‐inferior temporal lobe spongiosis. Reduced perfusion temporal, frontal and occipital lobes 5 in total Behavioral symptoms OCD, checking obsession and compulsions pinching people, tapping doors and tables + frequent mood changes. Senseless and intrusive aggressive thoughts + repetitive mental rituals. Number obsessions, compulsions with counting, intrusive thoughts about other aneurysms + MCI. Personality changes, increased apathy & withdrawal, memory impairment, senseless & intrusive thoughts about possible harm + symptoms of depression. Personality changes, apathy, little/no insight, intrusive musical tune played in her mind. Table 9. Case reports on involvement of the cerebellum Nr. Cases 1 1 2 in total Article Gonzalez et al., 1998* Ward, 1988 M/F F(77) F(62) Main site of lesion Behavioral symptoms Calcified mass in right posterior OCB: checking and washing fossa (displacement cerebellum) Lacunar infarcts in the right superior Urge to shake her right arm cerebellar peduncle and left basal ganglia * means exclusively involved Table 10. Case reports on involvement of the brainstem Brain area Nr. Cases Article M/F Main site of lesion Behavioral symptoms Unspecified 1 Gonzalez et al., 1998 Mordecai et al., 2000 F(77) Calcified mass in right posterior fossa (displacement cerebellum) Bilateral lesions basal ganglia + abnormalities in the internal capsula, frontal lobes, peduncles and pons OCB: checking and washing 1 M(13) OCD‐symptoms (need to say, repetition), mood lability, aggression, suicidal ideation, delusions and left hemiparesis OCD – contamination fear 1 Weiss & Jenike, 2000 F(56) Abnormalities bilateral frontal periventricular white matter, + in the central pons 1 Peterson et al., 1996 M(12) Hydrocephalus through a right tectal lesion involving the periaqueductal gray, right red nucleus, right thalamus, right subthalamic nuclei OCD (checking, ordering, list making and ritualized behaviours) ADHD; motor and vocal tics; nightmares and depression Periaqueductal 1 grey Total 4 Peterson et al., 1996 (see red nucleus case) Red Nucleus AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 25 Discussion Lesion studies on a total of 57 patients with acquired OCD were reviewed in order to obtain a better understanding of the neurological substrates involved in OCD that can be targeted with DBS. The high number of OCD cases following lesions of the basal ganglia, prefrontal cortex and thalamus confirm involvement of the CSTC‐circuit in the pathogenesis of OCD. In addition, onset of OCD was often reported following lesions of the cerebellum, brainstem, parietal and temporal cortices. Pathology of the CSTC circuit has often been linked to OCD symptomatology before, and DBS has proved to be effective in several key areas within this circuit (Insel, 1992; e.g. Gabriels et al., 2003). However, much less is known about how various brain structures within the CSTC‐circuit are related to distinct obsessive‐compulsive symptoms. The reviewed case reports show that brain injury involving (parts of) the basal ganglia and frontal lobe cause obsessive‐compulsive symptoms. These symptoms consisted mostly of ‘needing to know’, checking, washing, doubting, contamination fears and stereotyped activities. Other behavioral symptoms were abulia, apathy, aggression, depression and deficits in initiative, in which the basal ganglia and frontal lobe also seem to take part. Furthermore, case reports of acquired OCD reveal involvement of several unexpected brain areas. Involvement of the parietal and temporal cortices in OCD might be explained by their role in the integration of sensory information and formation of memories. For example, it can be hypothesized that disturbed memory formation in the temporal cortex is importantly involved in the habitual and repetitive character of obsessions and compulsions. Of note, checking and doubting were often observed following temporal lobe lesions. Checking and doubting could be associated with distrusting memory (van den Hout & Kindt, 2003 and 2004). The cerebellum is typically involved in learning motor sequences (Gómez‐Beldarrain et al., 1998). Cerebellar lesions were related to stereotyped, automatic motor activities, such as an exaggerated startle response, and dysphasia (Gonzalez & Philpot, 1998; Ward, 1988). Lastly, the brainstem, which among other functions regulates autonomic processes, was found to take part in acquired OCD. Through its function, the brainstem could have a lot of impact on OCD. For example through the serotonergic neural networks of the raphe nuclei whose ascending efferents project to several cerebral structures involved in OCD, e.g. the caudate nucleus and putamen. Nolfe et al. (1998) found involvement of the brainstem in OCD pathogenesis through electrophysiological data. Limitations and strengths In reviewing these case reports about acquired OCD, several limitations and strengths were noticed. First of all, in many reports it was not clear whether the same brain area boundaries were used in analyzing the imaging data of different case reports. Second, not every author gave detailed descriptions of the involved brain areas, for instance specification of parts of the basal ganglia. Third, the cases described here are most likely just a small sample, not representing the total population. Fourth, it could be that some of the brain AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 26 structures described in these case reports were not primarily related to OCD, or that these brain structures just influenced other areas that were essential to the etiology of OCD. Another point to take into consideration is that not all brain areas might have been properly examined in these case‐studies. Possibly, not every part of the brain was considered to be involved, which creates a bias. However, the amount and uniformity of these cases do not suggest that. Also, studies on diseases that affect the basal ganglia, like Parkinson’s and Huntington’s disease, which could result in similar symptoms, confirm the involvement of the suggested brain areas. A striking finding in the case reports was that several cases showed obsessive‐compulsive symptoms without anxiety, or with a lack of initiative or merely showing abulia or just stereotypic activities. Although these patients still met the criteria for OCD, they also showed some abnormalities from the OCD‐profile. One explanation for this deviated OCD profile could be that brain injury is not restricted to certain boundaries. More brain tissue could be damaged than necessary for causing the obsessive‐compulsive symptoms and this expansion could explain the abnormalities from the OCD‐profile. Another explanation for the abnormal OCD‐
profiles was recently suggested. Current reviews (Fineberg et al, 2010) introduce the concept of ‘compulsivity’, which can be understood in several ways. First, it is a tendency to perform repetitive acts in a habitual/stereotyped manner in an attempt to prevent adverse consequences. A newer definition states compulsivity as “the alleviation of an aversive contingency such as withdrawal” (Fineberg et al., 2010). The last definition tries to cover the overlap which has been noticed in a hypothesized impulsivity‐compulsivity continuum. Data from studies investigating disorders of impulsive and/or compulsive nature show a complicated interaction between involved brain structures and circuits. Looking at the results of the reviewed case reports, the variety of obsessive compulsive symptoms seen after brain injury seem to be better included within the concept of ‘compulsivity’ than just calling it OCD. Particularly when we consider the amount of case reports which show abulia, or just stereotypic behavior, or obsessive‐compulsive symptoms without anxiety. An example can be found in Donovan & Barry (1994), who reported obsessive‐compulsive symptoms after injury to the frontal lobes and the basal ganglia, which were devoid of anxiety. With the introduction of the concept of compulsivity, it became clear that the definition and current concept of OCD did not sufficiently encompassed its complex behavior. For example, the role of anxiety within OCD has been discussed and different opinions are noticed. Fineberg et al. (2010) suggested that logically anxiety would not be involved in OCD. On the contrary, McGuire (1995) described that resistance and anxiety are invariably associated with obsessions and compulsions in OCD. Based on the fact that during phobic anxiety as well as in OCD increased activity was found in the inferior prefrontal and anterior cingulate cortex, he suggested that changed activity in the inferior prefrontal and anterior cingulate cortex is associated with OCD and anxiety. In addition to the notion of compulsivity, several dimensions of OCD symptoms have been found. Factor‐analyses have found five different subtypes (Mataix‐Cols et al. 2005), namely 1) symmetry and order; 2) collecting; 3) contamination and cleaning, ‘hosophobia’; 4) somatic obsessions and checking; 5) sexual, religious and aggressive obsessions. Recently, it is suggested that each OCD symptom dimension has AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 27 its own neuro‐anatomical substrate (van den Heuvel et al., 2009). A new approach seems necessary to further understand the set of problems we call OCD. Perhaps the ‘compulsivity’ approach could be useful here. Also, future research should consider the validity of findings that do not distinguish different subtypes of OCD. It is recommended that future research should use more standardized methods to induce more replicable results. Also a combination of methods, like fMRI & EEG, should give more insight in the nature and time span of obsessions and compulsions. Furthermore, future research could focus more on the resistance to obsessional urges. This phenomenon has received less attention, but it would be interesting to study why resistance to obsessions cannot be achieved in OCD. McGuire (1995) suggested a link with inferior prefrontal activity. In some ways, obsessive compulsive symptoms could also be linked to neurological substrates involved in addiction as was also hypothesized in Fineberg et al. (2010). Investigating these case reports, several cases were found in which OCD‐symptoms disappeared after brain injury, e.g. Yaryura‐Tobias & Neziroglu (2003) who described a case of OCD remission following left putamen hemorrhage. It would be interesting to review these cases on the injured brain regions and to compare them to sites of deep brain stimulation. This could lead to new DBS targets, as this shows direct evidence that changed brain activity can ‘cure’ patients with OCD. In conclusion, a total of 57 patients with acquired OCD confirm involvement of the CSTC‐circuit in OCD pathogenesis. Lesions in several additional brain regions were also related to OCD, such as the cerebellum, brainstem, parietal and temporal cortices. These findings warrant further research into the role of these areas in OCD, particularly considering them as potential targets for DBS. 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(1999). The epidemiology of obsessive‐compulsive disorder in children en adolescents. Child and Adolescence Psychiatric Clinics of North America, 8(3), 445‐460 AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 35 Addendum Table 11. Overview of 58 cases with their findings and involved brain areas Author (Fe)Male Age Main site of lesion Behavioral symptoms 1 Carmin et al., 2002 Male 78 Two infarcts basal ganglia 2 Chacko et al., 2000 Chacko et al., 2000 Woman 76 Infarcts basal ganglia bilateral Woman 61 Bilateral basal ganglia infarcts 4 Chacko et al., 2000 Woman 77 Right basal ganglia infarction 5 Chacko et al., 2000 Chacko et al., 2000 Woman 70 Woman 77 ‘Needing to know’ obsessions and resulting checking rituals, phobic avoidance Obsessive‐compulsive behavior (OCB) (spouse infidelity) Obsessive‐compulsive behavior (OCB) (counting/hair combing ) + depressed mood Obsessive‐compulsive behavior (OCB) (fear of harming)+ psychiatric symptoms Obsessive‐compulsive behavior (OCB) (checking/ordering)+ depression Obsessive‐compulsive behavior (OCB) (dental disease)+ depressed mood 3 7 Daniele et al., 1997 Female 63 Bilateral basal ganglia calcification Ischaemic changes head of the right caudate, right lateral frontal convexity and the left lateral parietal convexity Left putamen 8 Demirkol et al., 1999 Donovan et al., 1994 Male 17 Bilateral globus pallidus lesions Male 22 Bilateral frontal lobe injury 10 Escalone et al., 1997 Male 34 Bilateral globus pallidus infarction 11 Fujii et al., 2005 Male 58 12 Gamazo‐Garran et al., 2002 Male 16 Left putaminal hemorrhage + probably involvement of lateral segment of the globus pallidus and tail of the caudate nucleus and limb of internal capsule Tumor affecting caudate nuclei 13 Giedd et al., 1996 Male 12 14 Gonzalez et al., 1998 Female 77 15 Hugo et al., 1999 Male 41 16 Hugo et al., 1999 Male 59 6 9 Compulsive symptoms (rhythmic activities, counting, need to read), devoid of anxiety, not associated with obsessions but egodystone + features of frontal lobe syndrome OCD: obsessions: thoughts of harming, sexual fantasies, contamination fear; compulsions: checking, washing and counting. + blunted affect + trichotillomania symptoms Started having OCD symptoms at 43 yrs, improvement after hemorrhage OCD, checking obsession and compulsions pinching people, tapping doors and tables + frequent mood changes Reduced basal ganglia size: 2 yr history of OCD: checking, size reduction of caudate, repeating behaviors, need for putamen and globus pallidus symmetry and excessive exercising. Calcified mass in right posterior OCB: checking and washing fossa (displacement cerebellum) Right frontal haematoma Intrusive checking thoughts and compulsions Bilateral anterior temporal and Obsessive doubt and compulsive AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 Obsessive thoughts (fear of what could happen to her children), later compulsions started (verbal iterations, coprolalia) + aggressive outbursts 3 yrs rituals: orderliness & washing 36 anterior frontal lobe atrophy Generalized atrophy + lacunar infarct right internal capsula Aneurysm left internal carotid artery Æ SPECT changes 17 Hugo et al., 1999 Male 32 18 Hugo et al., 1999 Female 46 19 Hugo et al., 1999 Male 41 Right anterior‐inferior temporal lobe spongiosis 20 Hugo et al., 1999 Female 29 Reduced perfusion temporal, frontal and occipital lobes 21 John et al., 1997 Male 53 Left frontal tumor 22 Kant et al., 1996 Male 43 Closed head injury 23 Kant et al., 1996 Male 26 Closed head injury 24 Kant et al., 1996 Male 16 25 Kant et al., 1996 Female 45 Closed head injury; right frontal fracture Closed head injury 26 Kim et al., 2002 Male 66 Infarct left OFC 27 Laplane et al., 1989 Male 53 28 Laplane et al., 1989 Male 23 29 Laplane et al., 1989 Laplane et al., 1989 Male 59 Male 52 31 Laplane et al., 1989 Female 27 32 Laplane et al., 1989 Male Bilateral lesions lentiform nucleus, small lesions caudate and putamen Bilateral globus pallidus, internal part of the lentiform nucleus Bilateral calcified lesions basal ganglia, mostly globus pallidus Bilateral lesions involving parts of the putamen, lateral pallidal segment and head of the caudate nucleus Bilateral lesions within the lentiform nuclei (almost whole globus pallidus) Bilateral lesions globus pallidus 33 Laplane et al., 1989 Female 31 34 Female 22 35 Laplane et al., 1989 Mahendran, 2000 Male 37 36 Mittal et al., 2010 Male 17 30 Bilateral lesion of the lentiform nuclei, anterior part of the globus pallidus Bilateral internal segment of the globus pallidus. Infarct involving the left frontal, temporal and parietal lobes – dilatation of frontal part of left lateral ventricle Small left‐sided basal ganglia AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 checking + symptoms of depression Senseless and intrusive aggressive thoughts + repetitive mental rituals Number obsessions, compulsions with counting, intrusive thoughts about other aneurysms + MCI Personality changes, increased apathy & withdrawal, memory impairment, senseless & intrusive thoughts about possible harm + symptoms of depression Personality changes, apathy, little/no insight, intrusive musical tune played in her mind Acute onset of anxiety and obsessional symptoms with verbal utterances. OCD: sexual and aggressive thoughts, fear of acting out. Mild depression, GAD Personality changes, checking & counting rituals, mild GAD and depression Counting & checking rituals Checking & counting, anxiety, cognitive deficits + major depression (paranoia) Obsessions ‘something wrong’ would happen and compulsive checking rituals ‘empty mind’, no depression, stereotyped activities (OCD), angry, not apparently anxious OCD ‐ mental stereotyped activities (counting), apparent lack of spontaneous activity Passivity, lack of initiative, no OCD Inactivity and lack of volition, no OCD Extremely inert; sad and pessimistic, subject to OC‐behavior and lack of inhibition No initiative, only when asked; polymorphic compulsive behavior (checking, counting, rituals); angry, not apparently anxious; major memory difficulties Psychopathic personality, impulsivity, OCD (counting, vocal repetitions) No OCD Compulsive symptoms & rituals, washing and bathing Æ only compulsions OCD (checking), stereotypic motor 37 stroke; tumor in the dorsal midbrain/pineal cistern; hydrocephalus Bilateral lesions basal ganglia + abnormalities in the internal capsula, frontal lobes, peduncles and pons Damage to the right frontal parietal area, removal tumor of the right parietal vertex, involving the superior sagittal sinus Bilateral caudate atrophy 37 Mordecai et al., 2000 Male 13 38 Paradis et al., 1992 Female 36 39 Patzold et al., 2002 Female 42 40 Peterson et al., 1996 Female 8 41 Peterson et al., 1996 Male 7 42 Peterson et al., 1996 Male 12 43 Scicutella, 2000 Male 72 44 Simpson et al., 1995 Male 71 45 Swoboda et al., 1995 Male 70 46 Thobois et al., 2004 Male 24 47 Tonkonogy et al., 1989 Female 36 48 Ward, 1988 49 Ward, 1988 Female Male 59 43 Frontoparietal tumor Left frontal mass 50 Ward, 1988 Female 62 51 Weilburg et al., 1989 Male 24 Lacunar infarcts in the right superior cerebellar peduncle and left basal ganglia Unilateral left‐sided abnormalities in the head of the caudate nucleus and putamen Resection of a tumor: injury involving the fornices bilaterally, 3rd ventricle, left hypothalamus, genu of left internal capsule, left caudate nucleus head, right cingulated gyrus, mid‐body corpus callosum Left parietal tumor involving the corpus callosum, left cingulate gyrus, fornix, left caudate nucleus Hydrocephalus through a right tectal lesion involving the periaqueductal gray, right red nucleus, right thalamus, right subthalamic nuclei Paraventricular white matter changes, possible basal ganglia lesion Right inferior parietal infarct Lower activity in right basal ganglia and temporal areas; more activity right OFC Infarct in the posterior right frontal region + extensions to deep subcortical white matter Hematoma of the left caudate nucleus, and anterior part of the putamen Atrophy of the caudate head and frontal lobe bilaterally AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 activities + depressions, psychotic symptoms OCD‐symptoms (need to say, repetition), mood lability, aggression, suicidal ideation, delusions and left hemiparesis OCD after removal tumor, contamination fears, washing rituals, need for symmetry and checking rituals. Ten yrs of Huntington’s disease Obsessive ideation, persistent thoughts of killing her neighbor, no additional compulsive symptoms Already developed tics – vocal, facial etc. After surgery, numerous repetitive stereotypies and compulsions Obsessive preoccupation with tactile stimuli Motor tics; Did not meet formal OCD criteria, but kept everything extremely neat OCD (checking, ordering, list making and ritualized behaviours) ADHD; motor and vocal tics; nightmares and depression Personality changes, anxiety & agitation, contamination fears, washing rituals (FTD & HD) OCD symptoms: needing to know and remember Acute onset of OCD (needing to know) symptoms Removal of the hematoma caused OCD (compulsive 10 letter sentences), no anxiety Compulsive hand‐washing, thoughts of cleanliness and contamination fear, excessive washing. Limited insight and agitated depression Æ OCD symptoms with increased atrophy Urge to walk to the left Urge to shake his right arm + sometimes shout Urge to shake her right arm Compulsion (hand‐washing), obsession (being ‘not clean’), dizziness and postural changes, episodes of depression 38 52 Weiss et al., 2000 Female 70 53 Weiss et al., 2000 Female 56 54 Weiss et al., 2000 Male 75 55 Weiss et al., 2000 Male 70 56 Weiss et al., 2000 Male 75 57 Williams et al., 1988 Female 48 58 Yaryura‐Tobias et al., 2003 Male 33 Abnormalities head of the left caudate nucleus + diffuse, mild cortical atrophy Abnormalities bilateral frontal periventricular white matter, + in the central pons Bilateral infarct caudate nucleus Infarct posterior right frontal lobe, extension to deep subcortical white matter No abnormalities, CT within normal limits Cavitation bilateral caudate nuclei, probably the putamen Left basal ganglia hemorrhage (left putamen) OCD – ‘something terrible’ would happen, history of depressive episode OCD – contamination fear OCD – infection & contamination worries, guilt OCD – ‘needing to know’ obsessions and compulsions OCD – ‘not right’ worries, recurrent depression Simulating typing exercise, depressive symptoms, likely lower intellectual functioning OCD disappeared due to hemorrhage – devoid of anxiety and depression, certain degree of apathy and indifference to his OCD AMC Psychiatrie, Angststoornissen – Ilse Wielaard, 3056953 39