David A. Seminowicz

Deep Brain Stimulation for Treatment-Resistant Depression

Treatment-resistant depression is a severely disabling disorder with no proven treatment options once multiple medications, psychotherapy, and electroconvulsive therapy have failed. Based on our preliminary observation that the subgenual cingulate region (Brodmann area 25) is metabolically overactive in treatment-resistant depression, we studied whether the application of chronic deep brain stimulation to modulate BA25 could reduce this elevated activity and produce clinical benefit in six patients with refractory depression. Chronic stimulation of white matter tracts adjacent to the subgenual cingulate gyrus was associated with a striking and sustained remission of depression in four of six patients. Antidepressant effects were associated with a marked reduction in local cerebral blood flow as well as changes in downstream limbic and cortical sites, measured using positron emission tomography. These results suggest that disrupting focal pathological activity in limbic-cortical circuits using electrical stimulation of the subgenual cingulate white matter can effectively reverse symptoms in otherwise treatment-resistant depression.

Two systems of resting state connectivity between the insula and cingulate cortex

The insula and cingulate cortices are implicated in emotional, homeostatic/allostatic, sensorimotor, and cognitive functions. Non‐human primates have specific anatomical connections between sub‐divisions of the insula and cingulate. Specifically, the anterior insula projects to the pregenual anterior cingulate cortex (pACC) and the anterior and posterior mid‐cingulate cortex (aMCC and pMCC); the mid‐posterior insula only projects to the posterior MCC (pMCC). In humans, functional neuroimaging studies implicate the anterior insula and pre/subgenual ACC in emotional processes, the mid‐posterior insula with awareness and interoception, and the MCC with environmental monitoring, response selection, and skeletomotor body orientation. Here, we tested the hypothesis that distinct resting state functional connectivity could be identified between (1) the anterior insula and pACC/aMCC; and (2) the entire insula (anterior, middle, and posterior insula) and the pMCC. Functional connectivity was assessed from resting state fMRI scans in 19 healthy volunteers using seed regions of interest in the anterior, middle, and posterior insula. Highly correlated, low‐frequency oscillations (< 0.05 Hz) were identified between specific insula and cingulate subdivisions. The anterior insula was shown to be functionally connected with the pACC/aMCC and the pMCC, while the mid/posterior insula was only connected with the pMCC. These data provide evidence for a resting state anterior insula–pACC/aMCC cingulate system that may integrate interoceptive information with emotional salience to form a subjective representation of the body; and another system that includes the entire insula and MCC, likely involved in environmental monitoring, response selection, and skeletomotor body orientation. Human Brain Mapp 2009.

Cortical responses to pain in healthy individuals depends on pain catastrophizing

Abstract The personal experience of pain is complex and depends on physiological and psychological factors. From this latter category, pain catastrophizing plays an important role in pain behavior and response. We aimed to determine the effect of pain catastrophizing on central nociceptive processing in healthy individuals. Functional MRI was performed during two pain intensity levels evoked by electrical median nerve stimulation in 22 healthy individuals. Pain catastrophizing scores were determined for all subjects. Pain catastrophizing was not related to activity in regions associated with sensory‐discriminative aspects of pain, such as the primary or secondary somatosensory cortex. Instead, during mild pain, there was a relationship between catastrophizing and activity in cortical regions associated with affective, attention, and motor aspects of pain, including dorsolateral prefrontal, insula, rostral anterior cingulate, premotor, and parietal cortices. During more intense pain, prefrontal cortical regions implicated in the top‐down modulation of pain were negatively correlated with catastrophizing. These findings can be viewed from the framework of an attention model of pain catastrophizing, whereby a cortical vigilance network is engaged during mild pain, but diminished prefrontal cortical modulation impedes disengaging from and suppressing pain during more intense pain. These findings may also implicate catastrophizing in the progression to or persistence of chronic pain.

State and trait influences on mood regulation in bipolar disorder: blood flow differences with an acute mood challenge.

BACKGROUND Even in remission, patients with bipolar disorder (BD) remain sensitive to external stressors that can trigger new episodes. Imitating such stressors by the controlled transient exposure to an emotional stimulus may help to identify brain regions modulating this sensitivity. METHODS Transient sadness was induced in 9 euthymic and in 11 depressed subjects with BD. Regional blood flow (rCBF) changes were measured using (15)O-water positron emission tomography. RESULTS Common changes in both groups were increased rCBF in anterior insula and cerebellum and decreased rCBF in dorsal-ventral-medial frontal cortex, posterior cingulate, inferior parietal, and temporal cortices. Decreases in dorsal ventral medial frontal cortices occurred in both groups, but subjects in remission showed a greater magnitude of change. Unique to remitted subjects with BD were rCBF increases in dorsal anterior cingulate and in premotor cortex. Lateral prefrontal rCBF decreases were unique to depressed subjects with BD. At baseline, remitted subjects showed a unique increase in dorsal anterior cingulate and orbitofrontal cortex. CONCLUSIONS Common rCBF changes in remitted and depressed subjects identifies potential sites of disease vulnerability. Unique cingulate and orbitofrontal changes both at baseline and with induced sadness seen in the absence of prefrontal rCBF decreases may identify regional interactions important to the euthymic state in this population.

A re-examination of pain-cognition interactions: implications for neuroimaging.

A drive circuit for an electroluminescent panel applies an AC voltage cycle at typical power cycle frequencies by increasing the voltage profile in discrete, pulsed steps at a rate which is at least one order of magnitude greater than the AC frequencies applied to power the panel. A transformer through which the power pulses are applied to the panel is of smaller size than state of the art resonant transformers for applying power cycles to electroluminescent panels. The reduced size of the transformer is advantageous in packaging the drive circuit in portable devices using electroluminescent panels. The voltage steps at the leading edge of the voltage excursions of the AC cycle applied to the panel may be programmably changed to adjust the light output of the panel, or to adjust the power applied by the circuit to correspond to the size of the panel to which the power is applied.