Obsessive-compulsive disorder (OCD) is characterized by repetitive thoughts and behaviours that are experienced as unwanted. Family and twin studies have demonstrated that OCD is a multifactorial ...familial condition that involves both polygenic and environmental risk factors. Neuroimaging studies have implicated the cortico-striato-thalamo-cortical circuit in the pathophysiology of the disorder, which is supported by the observation of specific neuropsychological impairments in patients with OCD, mainly in executive functions. Genetic studies indicate that genes affecting the serotonergic, dopaminergic and glutamatergic systems, and the interaction between them, play a crucial part in the functioning of this circuit. Environmental factors such as adverse perinatal events, psychological trauma and neurological trauma may modify the expression of risk genes and, hence, trigger the manifestation of obsessive-compulsive behaviours.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Obsessive-compulsive disorder (OCD) affects approximately 2–3% of the population and is characterized by recurrent intrusive thoughts (obsessions) and repetitive behaviors or mental acts ...(compulsions), typically performed in response to obsessions or related anxiety. In the past few decades, the prevailing models of OCD pathophysiology have focused on cortico-striatal circuitry. More recent neuroimaging evidence, however, points to critical involvement of the lateral and medial orbitofrontal cortices, the dorsal anterior cingulate cortex and amygdalo-cortical circuitry, in addition to cortico-striatal circuitry, in the pathophysiology of the disorder. In this review, we elaborate proposed features of OCD pathophysiology beyond the classic parallel cortico-striatal pathways and argue that this evidence suggests that fear extinction, in addition to behavioral inhibition, is impaired in OCD.
Psychiatric neurosurgery, specifically stereotactic ablation, has continued since the 1940s, mainly at a few centers in Europe and the US. Since the late 1990s, the resurgence of interest in this ...field has been remarkable; reports of both lesion procedures and the newer technique of deep brain stimulation (DBS) have increased rapidly. In early 2009, the US FDA granted limited humanitarian approval for DBS for otherwise intractable obsessive-compulsive disorder (OCD), the first such approval for a psychiatric illness. Several factors explain the emergence of DBS and continued small-scale use of refined lesion procedures. DBS and stereotactic ablation have been successful and widely used for movement disorders. There remains an unmet clinical need: current drug and behavioral treatments offer limited benefit to some seriously ill people. Understandings of the neurocircuitry underlying psychopathology and the response to treatment, while still works in progress, are much enhanced. Here, we review modern lesion procedures and DBS for OCD in the context of neurocircuitry. A key issue is that clinical benefit can be obtained after surgeries targeting different brain structures. This fits well with anatomical models, in which circuits connecting orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), basal ganglia, and thalamus are central to OCD pathophysiology and treatment response. As in movement disorders, dedicated interdisciplinary teams, here led by psychiatrists, are required to implement these procedures and maintain care for patients so treated. Available data, although limited, support the promise of stereotactic ablation or DBS in carefully selected patients. Benefit in such cases appears not to be confined to obsessions and compulsions, but includes changes in affective state. Caution is imperative, and key issues in long-term management of psychiatric neurosurgery patients deserve focused attention. DBS and contemporary ablation also present different patterns of potential benefits and burdens. Translational research to elucidate how targeting specific nodes in putative OCD circuitry might lead to therapeutic gains is accelerating in tandem with clinical use.
Abstract Recent rodent studies suggest that gonadal hormones influence extinction of conditioned fear. Here we investigated sex differences in, and the influence of estradiol and progesterone on, ...fear extinction in healthy humans. Men and women underwent a two-day paradigm in which fear conditioning and extinction learning took place on day 1 and extinction recall was tested on day 2. Visual cues were used as the conditioned stimuli and a mild electric shock was used as the unconditioned stimulus. Skin conductance was recorded throughout the experiment and used to measure conditioned responses (CRs). Blood samples were obtained from all women to measure estradiol and progesterone levels. We found that higher estradiol during extinction learning enhanced subsequent extinction recall but had no effects on fear acquisition or extinction learning itself. Sex differences were only observed during acquisition, with men exhibiting significantly higher CRs. After dividing women into low- and high-estradiol groups, men showed comparable extinction recall to high-estradiol women, and both of these groups showed higher extinction recall than low-estradiol women. Therefore, sex differences in extinction memory emerged only after taking into account women's estradiol levels. Lower estradiol may impair extinction consolidation in women. These findings could have practical applications in the treatment of anxiety disorders through cognitive and behavioral therapies.
Background A clinical characteristic of posttraumatic stress disorder (PTSD) is persistently elevated fear responses to stimuli associated with the traumatic event. The objective herein is to ...determine whether extinction of fear responses is impaired in PTSD and whether such impairment is related to dysfunctional activation of brain regions known to be involved in fear extinction, viz., amygdala, hippocampus, ventromedial prefrontal cortex (vmPFC), and dorsal anterior cingulate cortex (dACC). Methods Sixteen individuals diagnosed with PTSD and 15 trauma-exposed non-PTSD control subjects underwent a 2-day fear conditioning and extinction protocol in a 3-T functional magnetic resonance imaging scanner. Conditioning and extinction training were conducted on day 1. Extinction recall (or extinction memory) test was conducted on day 2 (extinguished conditioned stimuli presented in the absence of shock). Skin conductance response (SCR) was scored throughout the experiment as an index of the conditioned response. Results The SCR data revealed no significant differences between groups during acquisition and extinction of conditioned fear on day 1. On day 2, however, PTSD subjects showed impaired recall of extinction memory. Analysis of functional magnetic resonance imaging data showed greater amygdala activation in the PTSD group during day 1 extinction learning. During extinction recall, lesser activation in hippocampus and vmPFC and greater activation in dACC were observed in the PTSD group. The magnitude of extinction memory across all subjects was correlated with activation of hippocampus and vmPFC during extinction recall testing. Conclusions These findings support the hypothesis that fear extinction is impaired in PTSD. They further suggest that dysfunctional activation in brain structures that mediate fear extinction learning, and especially its recall, underlie this impairment.
The prefrontal cortex and OCD Ahmari, Susanne E; Rauch, Scott L
Neuropsychopharmacology,
01/2022, Letnik:
47, Številka:
1
Journal Article
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Obsessive Compulsive Disorder (OCD) is a highly prevalent and severe neuropsychiatric disorder, with an incidence of 1.5-3% worldwide. However, despite the clear public health burden of OCD and ...relatively well-defined symptom criteria, effective treatments are still limited, spotlighting the need for investigation of the neural substrates of the disorder. Human neuroimaging studies have consistently highlighted abnormal activity patterns in prefrontal cortex (PFC) regions and connected circuits in OCD during both symptom provocation and performance of neurocognitive tasks. Because of recent technical advances, these findings can now be leveraged to develop novel targeted interventions. Here we will highlight current theories regarding the role of the prefrontal cortex in the generation of OCD symptoms, discuss ways in which this knowledge can be used to improve treatments for this often disabling illness, and lay out challenges in the field for future study.
IMPORTANCE Obsessive-compulsive disorder (OCD) may be characterized by impaired self-regulation and behavioral inhibition. Elevated fear and anxiety are common characteristics of this disorder. The ...neurobiology of fear regulation and consolidation of safety memories have not been examined in this patient population. OBJECTIVE To examine the psychophysiological and neurobiological correlates of conditioned fear extinction in patients with OCD. DESIGN Cross-sectional, case-control, functional magnetic resonance imaging study. SETTING Academic medical center. PARTICIPANTS Twenty-one patients with OCD and 21 healthy participants. MAIN OUTCOMES AND MEASURES Skin conductance responses and blood oxygenation level–dependent responses. RESULTS The between-group difference noted in our psychophysiological measure (skin conductance responses) was during extinction recall: patients with OCD showed impaired extinction recall relative to control subjects. Regarding the functional magnetic resonance imaging data, patients with OCD showed significantly reduced activation in the ventromedial prefrontal cortex across training phases. Moreover, reduced activation in the patients with OCD was noted in the caudate and hippocampus during fear conditioning, as well as in the cerebellum, posterior cingulate cortex, and putamen during extinction recall. Contrary to our prediction, OCD symptom severity was positively correlated with the magnitude of extinction memory recall. Also contrary to our prediction, functional responses of the ventromedial prefrontal cortex were positively correlated with symptom severity, and functional responses of the dorsal anterior cingulate cortex were inversely correlated with symptom severity. CONCLUSIONS AND RELEVANCE As expected, our study showed that fear extinction and its neural substrates are impaired in patients with OCD. However, this study also yielded some surprising and unexpected results regarding the correlates between extinction capacity and its neural substrates and the severity of symptoms expressed in this disorder. Thus, our data report neural correlates of deficient fear extinction in patients with OCD. The negative correlations between fear extinction deficits and Yale-Brown Obsessive-Compulsive Scale symptoms in OCD suggest that there may be other factors, in addition to fear extinction deficiency, that contribute to the psychopathology of OCD.
There is at present limited understanding of the neurobiological basis of the different processes underlying emotion perception. We have aimed to identify potential neural correlates of three ...processes suggested by appraisalist theories as important for emotion perception: 1) the identification of the emotional significance of a stimulus; 2) the production of an affective state in response to 1; and 3) the regulation of the affective state. In a critical review, we have examined findings from recent animal, human lesion, and functional neuroimaging studies. Findings from these studies indicate that these processes may be dependent upon the functioning of two neural systems: a ventral system, including the amygdala, insula, ventral striatum, and ventral regions of the anterior cingulate gyrus and prefrontal cortex, predominantly important for processes 1 and 2 and automatic regulation of emotional responses; and a dorsal system, including the hippocampus and dorsal regions of anterior cingulate gyrus and prefrontal cortex, predominantly important for process 3. We suggest that the extent to which a stimulus is identified as emotive and is associated with the production of an affective state may be dependent upon levels of activity within these two neural systems.
To date, there has been little investigation of the neurobiological basis of emotion processing abnormalities in psychiatric populations. We have previously discussed two neural systems: 1) a ventral ...system, including the amygdala, insula, ventral striatum, ventral anterior cingulate gyrus, and prefrontal cortex, for identification of the emotional significance of a stimulus, production of affective states, and automatic regulation of emotional responses; and 2) a dorsal system, including the hippocampus, dorsal anterior cingulate gyrus, and prefrontal cortex, for the effortful regulation of affective states and subsequent behavior. In this critical review, we have examined evidence from studies employing a variety of techniques for distinct patterns of structural and functional abnormalities in these neural systems in schizophrenia, bipolar disorder, and major depressive disorder. In each psychiatric disorder, the pattern of abnormalities may be associated with specific symptoms, including emotional flattening, anhedonia, and persecutory delusions in schizophrenia, prominent mood swings, emotional lability, and distractibility in bipolar disorder during depression and mania, and with depressed mood and anhedonia in major depressive disorder. We suggest that distinct patterns of structural and functional abnormalities in neural systems important for emotion processing are associated with specific symptoms of schizophrenia and bipolar and major depressive disorder.
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