Right and left dorsolateral pre-frontal rTMS treatment of refractory depression: a randomized, sham-controlled trial.

We conducted a prospective, randomized, sham-controlled, double blind, parallel group study of right or left pre-frontal rTMS in 48 subjects with medication-resistant depression. Two thousand (50x8-s trains of 5Hz) stimuli at MEP threshold were delivered each weekday for 2weeks. We employed a sham coil and simultaneous electrical stimulation of the scalp to simulate rTMS. Mean (+/-S.D.) reductions in the HAMD-24 from baseline to 3-months were not significantly different between rTMS and sham treatment groups. However, right cranial stimulation (sham or rTMS) was significantly more effective than left cranial stimulation (sham or rTMS) (P=0.012). Mean (+/-S.D.) reductions in the HAMD from baseline to 3 months were: left: 28.1 (+/-5.36) to 19.2 (+/-11.2); and right 27.2 (+/-4.2) to 11.5 (+/-9.4). Left rTMS achieved a reduction in HAMD 9.5 points greater than that achieved by left sham, a benefit greater than that reported in a recent multi-center Phase III trial of rTMS (O'Reardon et al., 2007), albeit not statistically significant. These results suggest that somatosensory stimuli that repeatedly engage the left hemisphere may be important to the achievement of therapeutic effect.

Identical neural risk factors predict cognitive deficit in dyslexia and schizophrenia.

In previous work, the authors found that an anatomical risk index created from the combination of 7 neuroanatomical measures predicted reading and oral language skills in individuals with learning disabilities. Individuals with small auditory brain structures and reduced asymmetry had more deficits than those with large structures and exaggerated asymmetry. In the present study, the same anatomical index predicted reading and other cognitive abilities in 45 individuals with chronic schizophrenia. The anatomical risk index was significantly associated with broad cognitive ability (Pearson r = .53, p < .0001), reading comprehension (r = .58, p < .0001), and a measure of nonverbal reasoning (r = .39, p < .01), but not with age, parental socioeconomic status, symptom measures, alcohol use, or processing speed. These findings support the prediction that reduced size and asymmetry in temporal lobe auditory cortex and cerebellum may not be specific risk factors for schizophrenia but for cognitive deficits that characterize a broad spectrum of developmental disorders.

Deep brain stimulation for intractable obsessive compulsive disorder: pilot study using a blinded, staggered-onset design.

BACKGROUND: Prior promising results have been reported with deep brain stimulation (DBS) of the anterior limb of the internal capsule in cases with severe obsessive compulsive disorder (OCD) who had exhausted conventional therapies. METHODS: In this pilot study, six adult patients (2 male; 4 female) meeting stringent criteria for severe (minimum Yale-Brown Obsessive Compulsive Scale [Y-BOCS] of 28) and treatment-refractory OCD had DBS electrode arrays placed bilaterally in an area spanning the ventral anterior limb of the internal capsule and adjacent ventral striatum referred to as the ventral capsule/ventral striatum. Using a randomized, staggered-onset design, patients were stimulated at either 30 or 60 days following surgery under blinded conditions. RESULTS: After 12 months of stimulation, four (66.7%) of six patients met a stringent criterion as "responders" (> or =35% improvement in the Y-BOCS and end point Y-BOCS severity < or =16). Patients did not improve during sham stimulation. Depressive symptoms improved significantly in the group as a whole; global functioning improved in the four responders. Adverse events associated with chronic DBS were generally mild and modifiable with setting changes. Stimulation interruption led to rapid but reversible induction of depressive symptoms in two cases. CONCLUSIONS: This pilot study suggests that DBS of the ventral capsule/ventral striatum region is a promising therapy of last resort for carefully selected cases of severe and intractable OCD. Future research should attend to subject selection, lead location, DBS programming, and mechanisms underpinning therapeutic benefits.