Advances in Neuroimaging: Impact on Psychiatric Practice

FUNCTIONAL NEUROIMAGING IN PSYCHIATRY
Dementing disorders

The most common use of functional neuroimaging in neuropsychiatry is in the evaluation of dementia. Cerebral perfusion studies (typically using SPECT) and cerebral glucose metabolism studies (using PET) have become an essential part of the diagnostic armamentarium for evaluating patients with dementia. Various dementias often show a characteristic pattern of hypoperfusion. For example, Alzheimer disease is associated with bilateral hypoperfusion in temporoparietal areas. Subdivisions of the frontotemporal dementias can also show differing patterns of cerebral hypoperfusion and hypometabolism. fMRI has recently been used to augment the ability to distinguish between healthy subjects and those with Alzheimer disease. Gazzaley and Small¹² cite numerous studies that have detected blood oxygen level–dependent fMRI signal differences in the hippocampi of subjects with Alzheimer disease and mild cognitive impairment compared with age-matched controls. Thus, fMRI has promise in detecting preclinical Alzheimer disease in those with memory complaints.

Interesting work is also being done with the use of DT-MRI. Persson and colleagues¹³ have shown a possible role for DT-MRI in predicting the progression to Alzheimer disease in those who are genetically susceptible. For instance, aberrations have been shown in white matter integrity in the posterior corpus callosum and the medial temporal lobe in nondemented apolipoprotein e4 homozygotes but not in persons who do not carry the gene.

Affective disorders

Several strategies are available to investigate the neural basis of mood disorders with functional neuroimaging. While being imaged, subjects perform a cognitive activation paradigm (such as a test of working memory). Alternatively, subjects can be imaged during a mood challenge paradigm, in which mood states are induced by emotionally valenced pictures, by reading emotionally laden vignettes, or by recalling emotional autobiographical events. By use of mood challenge and cognitive paradigms, areas of activation can be compared between patients with mood disorders and matched normal controls.¹⁴

Mayberg and colleagues¹⁵ have put forward an influential view in which depression results from a dysfunction of limbic-cortical circuits. In their model, cognitive and attentional disturbances in depression result from decreased functioning of the dorsal compartment (the dorsolateral prefrontal cortex, the dorsal anterior cingulate, and the posterior cingulate), whereas vegetative and emotional symptoms result from increased activity in the ventral compartment (the subgenual anterior cingulate, the ventral prefrontal cortex, the insula, the hippocampus, and the amygdala).^14,16

The investigators also describe a rostral compartment (consisting of the rostral anterior cingulate) that serves to regulate the other 2 compartments in this circuit. Neuroimaging studies appear to be consistent with their model. For example, numerous studies of cerebral glucose metabolism and regional cerebral blood flow have shown hypometabolism and hypoperfusion in the dorsal compartment prefrontal areas.¹⁵

fMRI studies in which sad states are induced in healthy controls also show decreased activity in these areas, specifically the dorsal anterior cingulate cortex and the dorsolateral prefrontal cortex.¹⁷ The same studies have also shown increased activity in ventral compartment areas, specifically the subgenual prefrontal, the pregenual anterior cingulate, and the ventral prefrontal cortices and the insula.¹⁷ The amygdala is also implicated in depression, and the intensity of amygdala activation in PET has been correlated with the severity of depression.¹⁸ Interestingly, other research has shown normalization of frontal metabolism with the treatment of depression.¹⁹

Involvement of specific brain areas in mania and hypomania are less well characterized than they are in unipolar depression.¹⁴ Functional imaging studies of individuals with bipolar illness have demonstrated dysfunction in frontal and striatal regions. In the resting state, there appears to be decreased regional cerebral blood flow in the ventromedial and orbitofrontal cortex.²⁰ Cognitive activation tasks have shown alterations in the recruitment of ventral prefrontal, dorsolateral prefrontal, and dorsal anterior cingulate regions.¹⁷ In the basal ganglia, increased activation during manic episodes has been reported in the caudate head.²¹ MRS studies have also implicated anomalies in second messenger systems in prefontal and striatal areas in bipolar patients.²² Specifically, such studies have revealed abnormalities in the concentration of choline and myoinositol (both critical in second messenger signaling) in the brains of bipolar patients.^23,24

Anxiety disorders

Models of the pathophysiology of obsessive-compulsive disorder (OCD) have implicated a cortical-striatal circuit, in which projections from the orbitofrontal and cingulate cortex to the striatum synapse in the globus pallidus and thalamus on their way back to the frontal cortex.¹⁴ Functional neuroimaging studies have revealed increased regional brain activity in the orbitofrontal cortex, caudate, thalamus, and anterior cingulate cortex in patients with OCD, both at rest and during symptom provocation.^14,25,26 These findings are consistent with theories that posit deficient gating of striatal input at the thalamic level causing increased activity in both the orbitofrontal cortex and anterior cingulate cortex in patients with OCD.^17,26

Functional imaging studies in patients with panic disorder that use lactate to induce panic attacks have shown widespread abnormalities in monoaminergic projection systems as well as more focal abnormalities in the medial temporal lobe.¹⁷ Studies of specific phobias have yielded more inconsistent results but suggest involvement of the medial temporal lobe.¹⁷

The functional imaging of posttraumatic stress disorder (PTSD) has demonstrated exaggerated amygdala activation and decreased activation of the medial frontal lobe during symptom provocation studies.^14,27 In addition, the extent of amygdala activation has been correlated with the severity of symptoms in PTSD.¹⁴