Dissociable patterns of neural activity during response inhibition in depressed adolescents with and without suicidal behavior.

OBJECTIVES: Impaired attentional control and behavioral control are implicated in adult suicidal behavior. Little is known about the functional integrity of neural circuitry supporting these processes in suicidal behavior in adolescence. METHOD: Functional magnetic resonance imaging was used in 15 adolescent suicide attempters with a history of major depressive disorder (ATTs), 15 adolescents with a history of depressive disorder but no suicide attempt (NATs), and 14 healthy controls (HCs) during the performance of a well-validated go-no-go response inhibition and motor control task that measures attentional and behavioral control and has been shown to activate prefrontal, anterior cingulate, and parietal cortical circuitries. Questionnaires assessed symptoms and standardized interviews characterized suicide attempts. RESULTS: A 3 group by 2 condition (go-no-go response inhibition versus go motor control blocks) block-design whole-brain analysis (p < .05, corrected) showed that NATs showed greater activity than ATTs in the right anterior cingulate gyrus (p = .008), and that NATs, but not ATTs, showed significantly greater activity than HCs in the left insula (p = .004) to go-no-go response inhibition blocks. CONCLUSIONS: Although ATTs did not show differential patterns of neural activity from HCs during the go-no-go response inhibition blocks, ATTs and NATs showed differential activation of the right anterior cingulate gyrus during response inhibition. These findings indicate that suicide attempts during adolescence are not associated with abnormal activity in response inhibition neural circuitry. The differential patterns of activity in response inhibition neural circuitry in ATTs and NATs, however, suggest different neural mechanisms for suicide attempt versus major depressive disorder in general in adolescence that should be a focus of further study.

Neural correlates of symptom dimensions in pediatric obsessive-compulsive disorder: a functional magnetic resonance imaging study.

OBJECTIVE: Neuroimaging studies have identified distinct neural correlates of obsessive-compulsive disorder (OCD) symptom dimensions in adult subjects and may be related to functional abnormalities in different cortico-striatal-thalamic neural systems underlying cognition and affective processing. Similar symptom dimensions are apparent in childhood and adolescence, but their functional neural correlates remain to be elucidated. METHOD: Pediatric subjects with OCD (n = 18) and matched controls (n = 18), ages 10 to 17 years, were recruited for two functional magnetic resonance imaging experiments. They were scanned while viewing alternating blocks of symptom provocation (contamination-related or symmetry-related) and neutral pictures and imagining scenarios related to the content of each picture type. RESULTS: The subjects with OCD demonstrated reduced activity in the right insula, putamen, thalamus, dorsolateral prefrontal cortex, and left orbitofrontal cortex (contamination experiment) and in the right thalamus and right insula (symmetry experiment). Higher scores on OCD symptom-related measures (contamination and total severity) were significantly predictive of reduced neural activity in the right dorsolateral prefrontal cortex during the contamination experiment. CONCLUSIONS: Our findings indicate reduced activity in neural regions underlying emotional processing, cognitive processing, and motor performance in pediatric subjects with OCD compared with the controls. These between-group differences are present during both contamination and symmetry provocation experiments and during symptom provocation as well as viewing neutral pictures. The direction of activity is in contrast to adult findings in the insula and in components of cortico-striatal-thalamic neural systems. Our findings suggest developmental effects on neural systems underlying symptom dimensions in pediatric OCD.

Reduced gray matter volume in ventral prefrontal cortex but not amygdala in bipolar disorder: significant effects of gender and trait anxiety.

Neuroimaging studies in bipolar disorder report gray matter volume (GMV) abnormalities in neural regions implicated in emotion regulation. This includes a reduction in ventral/orbital medial prefrontal cortex (OMPFC) GMV and, inconsistently, increases in amygdala GMV. We aimed to examine OMPFC and amygdala GMV in bipolar disorder type 1 patients (BPI) versus healthy control participants (HC), and the potential confounding effects of gender, clinical and illness history variables and psychotropic medication upon any group differences that were demonstrated in OMPFC and amygdala GMV. Images were acquired from 27 BPI (17 euthymic, 10 depressed) and 28 age- and gender-matched HC in a 3T Siemens scanner. Data were analyzed with SPM5 using voxel-based morphometry (VBM) to assess main effects of diagnostic group and gender upon whole brain (WB) GMV. Post-hoc analyses were subsequently performed using SPSS to examine the extent to which clinical and illness history variables and psychotropic medication contributed to GMV abnormalities in BPI in a priori and non-a priori regions has demonstrated by the above VBM analyses. BPI showed reduced GMV in bilateral posteromedial rectal gyrus (PMRG), but no abnormalities in amygdala GMV. BPI also showed reduced GMV in two non-a priori regions: left parahippocampal gyrus and left putamen. For left PMRG GMV, there was a significant group by gender by trait anxiety interaction. GMV was significantly reduced in male low-trait anxiety BPI versus male low-trait anxiety HC, and in high- versus low-trait anxiety male BPI. Our results show that in BPI there were significant effects of gender and trait-anxiety, with male BPI and those high in trait-anxiety showing reduced left PMRG GMV. PMRG is part of medial prefrontal network implicated in visceromotor and emotion regulation.

Supplementary motor area and presupplementary motor area: targets of basal ganglia and cerebellar output.

We used retrograde transneuronal transport of neurotropic viruses in Cebus monkeys to examine the organization of basal ganglia and cerebellar projections to two cortical areas on the medial wall of the hemisphere, the supplementary motor area (SMA) and the pre-SMA. We found that both of these cortical areas are the targets of disynaptic projections from the dentate nucleus of the cerebellum and from the internal segment of the globus pallidus (GPi). On average, the number of pallidal neurons that project to the SMA and pre-SMA is approximately three to four times greater than the number of dentate neurons that project to these cortical areas. GPi neurons that project to the pre-SMA are located in a rostral, "associative" territory of the nucleus, whereas GPi neurons that project to the SMA are located in a more caudal and ventral "sensorimotor" territory. Similarly, dentate neurons that project to the pre-SMA are located in a ventral, "nonmotor" domain of the nucleus, whereas dentate neurons that project to the SMA are located in a more dorsal, "motor" domain. The differential origin of subcortical projections to the SMA and pre-SMA suggests that these cortical areas are nodes in distinct neural systems. Although both systems are the target of outputs from the basal ganglia and the cerebellum, these two cortical areas seem to be dominated by basal ganglia input.