MR-based perfusion imaging in OCD is rare. A study examined the changes in rCBF during symptom provocation and reported most changes in the orbitofrontal-subcortical circuits (i.e., elevated rCBF in the orbitofrontal cortex, caudate nucleus , and thalamus) [43]. Lower CBF in the orbitofrontal cortex and higher rCBF in the posterior cingulate predicted better treatment response. OCD has been more commonly studied using nuclear medicine-based perfusion imaging. Increased perfusion was reported in the right orbitofrontal cortex, bilateral frontal cortex, left premotor cortex, and left precuneus. Based on the findings of perfusion imaging, the orbitofrontal cortex seems to the key region involved in OCD. Therefore, elevated orbitofrontal CBF during symptom provocation may be specific to OCD.

FDG PET is ideally suited to map the dysfunctional cortico-striato-thalamo-cortical circuitry previously reported in OCD. Increased metabolism in the orbital gyrus, caudate nuclei, and cingulate gyrus, suggests dysfunction in these regions in OCD. Stimulation of a ventral striatum/ventral capsule target has been shown to significantly activate the orbitofrontal and anterior cingulate cortices, striatum, globus pallidus, and thalamus [44]. Furthermore, metabolic studies have shown that stimulation of the anterior capsule induced a decrease in prefrontal metabolic activity, especially in the subgenual ACC, which is considered to reflect an interruption of the cortico-thalamo-striato-cortical circuit. In addition, the degree of improvement in OCD inversely correlated with the metabolism of the left ventral striatum, amygdala, and hippocampus. All these findings support a major role for the dysfunction of the limbic circuits in OCD pathophysiology and show that DBS modulates these pathways [45] (Figs. 3.3 and 3.4).

Neuroimaging is routinely used for workup of patients with psychotic disorders because lesions in the frontal or temporal lobes, most often tumors, can present with psychosis [46]. In older people with cognitive impairment, it may be difficult to differentiate a neurodegenerative disorder from depression. Neuroimaging may be helpful in this situation by revealing characteristic of Alzheimer’s disease (AD), diffuse Lewy body disease, or one of the fronto-temporal dementias. Neuroimaging for psychiatric disorders has to contend with the diagnostic issues in psychiatry. The neurobiology of psychiatric disorders is likely to be highly heterogeneous. Thus, the neuroimaging findings in psychiatric disease may lack specificity and often fail to reveal a clear connection to a single neurobiological disturbance. Currently, the neuroimaging pattern determined in a study of a single patient with a psychiatric condition does not allow for an accurate diagnosis. Some characteristic findings, however, have been derived from samples of patients with each of the psychiatric diagnostic groupings [16].

Neuroimaging can be helpful at several levels of drug discovery and development [47]: (1) characterizing preclinical models; (2) conducting early clinical studies to show that target engagement by the new drug induces the biological changes expected to give clinical benefit; (3) evaluating patients in clinical trials to demonstrate proof of concept. In other words, engaging a particular target can be shown to be linked to a meaningful change in a clinical endpoint observable via neuroimaging, thus providing evidence supporting the treatment being studied. Since neuroimaging can likely enable in vivo observation of brain structure and function, it could potentially provide ideal biomarkers for therapeutic intervention development. Considering the definition of biomarker [47], most neuroimaging methods do not meet the biomarker standards for now. However, some methods have the potential to be used as biomarkers or pre-biomarkers because they allow for identification of therapy-relevant characteristics of the disease. For instance, by examining striatal DA D2 receptors in a [¹¹C]raclopride PET scan, a link was found between D2 receptor occupancy by a drug and a reduction in the positive symptoms in schizophrenia; ascending doses of up to 80 % receptor occupancy were progressively more effective in relieving delusions and hallucinations [48].

In a conclusion, neuroimaging is being increasingly applied for the development of psychiatric therapies. Neuroimaging is clinically relevant for diagnosis and differential diagnosis. It can yield further insights into the mechanisms of psychiatric diseases. Neuroimaging provides the pre-clinical researcher a relatively easy method to test whether a potential drug target shows an abnormality in a psychiatric disorder and whether, therefore, its correction may be therapeutic. Finally, by identifying the individuals who manifest the expected pharmacological action of the drug, neuroimaging can aid in personalized medicine by selecting individuals most likely to benefit from a particular treatment in a clinical trial.