Functional magnetic resonance imaging study of regional brain activation during implicit sequence learning in obsessive-compulsive disorder.

BACKGROUND: Corticostriatal circuitry has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). The serial reaction time (SRT) task, a paradigm that tests implicit sequence learning, has been used with imaging to probe striatal function. Initial studies have indicated that OCD patients exhibit deficient striatal activation and aberrant hippocampal recruitment compared with healthy control (HC) subjects. Here, we used the SRT and functional magnetic resonance imaging (fMRI) to replicate prior results in a larger sample and to test for relationships between regional activation and OCD symptom dimensions. METHODS: Using SPM99, fMRI-SRT data from 12 OCD and 12 matched HC subjects were analyzed. Symptom dimensions followed a four-factor model scored on a 0- to 10-point scale. RESULTS: For the implicit learning versus random contrast, group by condition interactions revealed aberrant recruitment within the hippocampus as well as orbitofrontal cortex (OCD > HC) but no striatal group differences. However, an inverse correlation was found between striatal activation and specific symptom factors. CONCLUSIONS: These results replicate previous smaller studies showing aberrant hippocampal recruitment in OCD during SRT performance. Although findings of deficient striatal activation in OCD were not replicated, correlation results suggest that this inconsistency may be attributable to differences among OCD symptom dimensions.

Evidence for reduced cerebellar volumes in trichotillomania.

BACKGROUND: Limited knowledge exists regarding the neurobiology of trichotillomania (TTM). Cerebellum (CBM) volumes were explored, given its role in complex, coordinated motor sequences. METHODS: Morphometric magnetic resonance imaging (MRI) scans were obtained for 14 female subjects with DSM-IV diagnoses of TTM and 12 age-, education-, and gender-matched normal control (NC) participants. Parcellation was performed utilizing a recently developed methodology to measure subterritory volumes of the CBM. Regions were defined based on knowledge of the structural and functional subunits of the CBM. RESULTS: As predicted, significant group differences were reported for CBM raw cortical volumes (p = .008) that survived correction for total brain volume (TBV; p = .037) and head circumference (HC; p = .011). A priori and post hoc group raw volume comparisons for CBM subterritories and functional clusters revealed many significant differences. However, most differences failed to withstand correction for total CBM volumes (TCV). Smaller volumes were consistently reported for the TTM versus NC cohorts. Total Massachusetts General Hospital Hair Pulling Scale (MGHHPS) scores were significantly inversely correlated with left primary sensorimotor cluster volumes (p = .008), with smaller volumes associated with more severe TTM symptoms. CONCLUSIONS: These findings implicate the CBM in the neurobiology of TTM, with reduced subterritory volumes reported for the TTM versus NC groups.

Brain activation during implicit sequence learning in individuals with trichotillomania.

Trichotillomania (TTM) may be related to obsessive-compulsive disorder (OCD) and other neuropsychiatric conditions characterized by cortico-striatal dysfunction. Functional imaging studies of OCD using an implicit learning task have found abnormalities in striatal and hippocampal activation. The current study investigated whether similar abnormalities occur in TTM. Functional MRI and the serial reaction time (SRT) task were used to assess striatal and hippocampal activation during implicit sequence learning in TTM and healthy control (HC) subjects. The results for 20 age- and education-matched participants (10 TTM, 10 HC) are reported. In comparison with HC participants, those with TTM exhibited no significant differences in implicit learning, or in activation within the striatum, hippocampus, or other brain regions. The current findings do not provide evidence for cortico-striatal dysfunction in TTM. Future studies directly comparing OCD and TTM subjects are warranted to confirm the specificity of abnormal striatal and hippocampal findings during implicit sequence learning in OCD.

A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder.

BACKGROUND: Previous functional neuroimaging studies have demonstrated exaggerated amygdala responses and diminished medial prefrontal cortex responses during the symptomatic state in posttraumatic stress disorder (PTSD). OBJECTIVES: To determine whether these abnormalities also occur in response to overtly presented affective stimuli unrelated to trauma; to examine the functional relationship between the amygdala and medial prefrontal cortex and their relationship to PTSD symptom severity in response to these stimuli; and to determine whether responsivity of these regions habituates normally across repeated stimulus presentations in PTSD. DESIGN: Case-control study. SETTING: Academic medical center. PARTICIPANTS: Volunteer sample of 13 men with PTSD (PTSD group) and 13 trauma-exposed men without PTSD (control group). MAIN OUTCOME MEASURES: We used functional magnetic resonance imaging (fMRI) to study blood oxygenation level-dependent signal during the presentation of emotional facial expressions. RESULTS: The PTSD group exhibited exaggerated amygdala responses and diminished medial prefrontal cortex responses to fearful vs happy facial expressions. In addition, in the PTSD group, blood oxygenation level-dependent signal changes in the amygdala were negatively correlated with signal changes in the medial prefrontal cortex, and symptom severity was negatively related to blood oxygenation level-dependent signal changes in the medial prefrontal cortex. Finally, relative to the control group, the PTSD group tended to exhibit diminished habituation of fearful vs happy responses in the right amygdala across functional runs, although this effect did not exceed our a priori statistical threshold. CONCLUSIONS: These results provide evidence for exaggerated amygdala responsivity, diminished medial prefrontal cortex responsivity, and a reciprocal relationship between these 2 regions during passive viewing of overtly presented affective stimuli unrelated to trauma in PTSD.

Brain correlates of negative visuospatial priming in healthy children.

Inhibitory mechanisms that begin to develop in childhood are essential for efficient and goal-directed behaviors. These inhibitory mechanisms may go awry in several childhood-onset neuropsychiatric disorders, such as Tourette syndrome, obsessive-compulsive disorder and attention deficit hyperactivity disorder. Negative visuospatial priming is a well-established behavioral probe of inhibition that has been used to demonstrate deficits in children with neuropsychiatric disorders of inhibition, but the brain correlates of negative visuospatial priming have not previously been well delineated. In the present study, we use a visuospatial priming paradigm and event-related functional magnetic resonance imaging (fMRI) to probe inhibitory brain mechanisms in healthy children. When subjects performed the control (i.e. neutral) motor task, a network of cortical and subcortical sensorimotor regions was activated. In contrast, during performance of the negative priming (i.e. inhibitory) task, several regions of the prefrontal cortex were selectively engaged. These results support the notion that the prefrontal cortex is involved in inhibitory processing in healthy children and demonstrate that negative visuospatial priming shares brain correlates with other inhibitory tasks. In conjunction with fMRI, the visuospatial priming task described in the current study may be useful for studying the pathophysiology of childhood-onset neuropsychiatric disorders characterized by deficient inhibitory processing.

Factors associated with potentially inappropriate drug utilization in a sample of rural community-dwelling older adults.

BACKGROUND: Many medications present special risks when used by older adults (ie, those aged > or = 65 years) and are considered potentially inappropriate for this population. The Beers criteria are often used to identify such medications. Past research has documented that use of Beers drugs is common among older adults. OBJECTIVE: The aim of this work was to examine factors associated with potentially inappropriate drug use among rural community-dwelling older adults using a conceptual framework adapted from the Andersen-Newman behavioral model of health service use. METHODS: This was a population-based, cross-sectional survey. Data were collected via face-to-face home interviews between 2002 and 2004. Rural community-dwelling older adults residing in a single county in North Carolina were eligible. Potentially inappropriate drug use was operationalized using the Beers criteria. Data concerning predisposing (ie, age, sex, race, education, and marital status), enabling (ie, social support and insurance status), need (ie, disability and history of major depression, hypertension, osteoarthritis, back problems, or other comorbidities), and utilization factors (ie, number of medications used) were collected. RESULTS: Data were gathered from 892 people, with information on medication use available for 800. Two hundred thirteen of these 800 participants (26.6%) used > or = 1 Beers drug. Compared with individuals who used no Beers drugs, those who used > or = 1 Beers drug reported lower levels of social support (odds ratio [OR], 0.94; 95% CI, 0.90-0.99) and higher levels of disability (OR, 1.48; 95% CI, 1.11-1.97), used more medications (OR, 1.07; 95% CI, 1.01-1.13), and were more likely to have a history of major depression (OR, 1.67; 95% CI, 1.05-2.66), hypertension (OR, 1.58; 95% CI, 1.07-2.33), osteoarthritis (OR, 1.58; 95% CI, 1.09-2.29), and back problems (OR, 1.72; 95% CI, 1.19-2.47). CONCLUSION: As suggested by the Andersen-Newman model, the risk of potentially inappropriate drug use is highest among those with the greatest medication needs, as evidenced by poorer health status in this sample of rural community-dwelling older patients.

Amygdala and insular responses to emotionally valenced human faces in small animal specific phobia.

BACKGROUND: Contemporary neurobiological models suggest that the amygdala plays an important role in the pathophysiology of anxiety disorders. However, it is not clear to what extent this concept applies across anxiety disorders. Several studies have examined brain function in specific phobias but did not demonstrate amygdala responses or use specific probes of the amygdala. METHODS: Ten subjects with specific small animal phobia and 10 matched control subjects were studied with functional magnetic resonance imaging. Subjects viewed emotionally expressive and neutral faces, and amygdala blood oxygenation level dependent responses from each group were compared. RESULTS: There was a significant response to the fearful versus neutral faces in the amygdala across both groups but no diagnosis x condition interaction. Post hoc analysis of the whole brain revealed a significantly greater response to the fearful versus neutral faces in the right insular cortex of the specific phobia group than in the control group. CONCLUSIONS: Amygdala hyperresponsivity to emotional faces was not observed in subjects with small animal specific phobia, in contrast to findings in other anxiety disorders (e.g., posttraumatic stress disorder). This suggests a restricted role for the amygdala in specific phobia. The insular hyperresponsivity to fearful versus neutral faces in the subjects with specific phobias warrants further study.

Differential amygdalar response to novel versus newly familiar neutral faces: a functional MRI probe developed for studying inhibited temperament.

BACKGROUND: As a prelude to future studies of subjects with different temperaments, we sought to develop a probe to measure differential amygdalar responses to novel versus familiar stimuli. Prior neuroimaging studies of the amygdala in humans to date have focused principally on responses to emotional stimuli, primarily aversive, rather than to novelty per se. METHODS: Eight normal subjects aged 22.4 +/- 1.3 years were scanned using functional magnetic resonance imaging (fMRI) during passive viewing of novel and familiar faces. RESULTS: Using this newly developed paradigm, we found greater fMRI blood oxygenation level dependent (BOLD) signal response within the right amygdala to novel versus familiar faces--all with neutral expression. Furthermore, although a new facial identity was always presented in the novel condition, signal in the amygdala declined over time as it did for the familiar condition. CONCLUSIONS: These results suggest that at least one primary function of the amygdala is to detect and process unexpected or unfamiliar events that have potential biological import, of which stimuli symbolic of fear or threat are but one possible example. We propose that this experimental paradigm will be useful for examining brain responses to novelty in different temperamental groups, as well as various psychiatric disorders.

Functional magnetic resonance imaging evidence for a lack of striatal dysfunction during implicit sequence learning in individuals with animal phobia.

OBJECTIVE: This study investigated the neural substrates of implicit sequence learning in subjects with and without small animal phobia, in a follow-up to analogous studies of obsessive-compulsive disorder (OCD). METHOD: Ten subjects with specific phobia and 10 healthy comparison subjects were studied by using a serial reaction time task paradigm and functional magnetic resonance imaging. RESULTS: A main effect of condition (implicit sequence learning versus random sequence) was observed across diagnostic groups in the right striatum, as well as in other regions. In the striatum, the a priori region of interest, there were no significant effects of diagnosis or the interaction of diagnosis and condition. CONCLUSIONS: Brain activation in the striatum of subjects with specific phobia does not significantly differ from that of normal comparison subjects during implicit sequence learning. This suggests different pathophysiological mechanisms for specific phobia in contrast to OCD, in which deficient striatal recruitment has been reproducibly found with this paradigm. This approach offers promise for demonstrating diagnostic specificity across different neuropsychiatric disorders based on the presence or absence of deficient striatal activation.

Selectively reduced regional cortical volumes in post-traumatic stress disorder.

Different subterritories of anterior cingulate cortex (ACC) and adjacent ventromedial frontal cortex have been shown to serve distinct functions. This scheme has influenced contemporary pathophysiologic models of psychiatric disorders. Prevailing neurocircuitry models of post-traumatic stress disorder (PTSD) implicate dysfunction within pregenual ACC and subcallosal cortex (SC), as well as amygdala and hippocampus. In the current study, cortical parcellation of magnetic resonance imaging data was performed to test for volumetric differences in pregenual ACC and SC, between women with PTSD and trauma-exposed women without PTSD. The PTSD group exhibited selectively decreased pregenual ACC and SC volumes. These results are consistent with contemporary schemes regarding functional and structural dissection of frontal cortex, and suggest specific regional cortical pathology in PTSD.

UNC certificate program in core public health concepts: lessons learned.

OBJECTIVES: Public health workers need to be trained in the core public health sciences. The University of North Carolina at Chapel Hill School of Public Health created a Certificate in Core Public Health Concepts to meet the training needs of public health workers, primarily those working in state or local public health agencies. METHODS: This article examines the demographic, educational, job classification, and workplace characteristics of certificate program applicants from the first 3 years of the program. In addition, this article assesses student performance and graduate satisfaction with the program. RESULTS: Among the 273 applications reviewed, the majority were from females. They worked in a variety of job classifications: 19% were public health agency workers, 64% were public health system workers, and 17% worked in other occupations. Nearly all students received High Pass or Pass grades on courses. Initial data on graduate satisfaction with the program are positive. CONCLUSIONS: Implications of the findings for training the public health workforce are discussed.

Brain correlates of negative and positive visuospatial priming in adults.

A balance of inhibitory and facilitatory mechanisms is essential for efficient and goal-directed behaviors. These mechanisms may go awry in several neuropsychiatric disorders characterized by uncontrolled, repetitive behaviors. The visuospatial priming paradigm is a well-established probe of inhibition and facilitation that has been used to demonstrate behavioral deficits in patients with Tourette syndrome and obsessive-compulsive disorder. However, the brain correlates of this visuospatial priming paradigm are not yet well established. In the present study, we used a visuospatial priming paradigm and event-related functional MRI, to probe inhibitory and facilitatory brain mechanisms in healthy adult women. When subjects performed the negative priming (i.e., inhibitory) task, several regions of the prefrontal cortex were selectively activated relative to the neutral condition. Non-overlapping regions of the prefrontal cortex were deactivated in the positive priming condition. These results support the notion that the prefrontal cortex is involved in both inhibitory and facilitatory processing and demonstrate that this visuospatial priming task shares brain correlates with other positive and negative priming tasks. In conjunction with functional MRI, this visuospatial priming task may be useful for studying the pathophysiology of neuropsychiatric disorders in which deficient inhibitory processing or excessive facilitation is a feature.

Novelty responses and differential effects of order in the amygdala, substantia innominata, and inferior temporal cortex.

Recent studies of amygdala function have focused on examining responses to emotionally valenced versus neutral stimuli. However, electrophysiologic and neuroimaging studies also suggest that novel neutral faces activate the amygdala, though few investigations have examined the effects of novelty and its relation to changes in stimulus condition. To further investigate how the human amygdala and related structures react to novel neutral faces and to stimulus condition changes, we evaluated human brain responses to blocks containing multiple novel and single repeated face stimuli, presented in two different orders, using functional magnetic resonance imaging (fMRI). Significantly increased signal was present in the amygdala, substantia innominata (SI), and inferior temporal cortex (ITC) to the contrast of multiple novel versus single faces. However, these regions differed in their responses based on whether a stimulus condition was presented 1st or 2nd, with the amygdala and SI having significantly different response profiles than the ITC. Specifically, greater responses to stimuli presented 2nd (i.e., after a condition change) were found in the amygdala and SI, but not in the ITC. Furthermore, the response difference to the Multiple versus Single contrast was greatest in the amygdala and SI, when single faces were presented 1st, and multiple faces presented 2nd, but this pattern was the reverse in the ITC. We speculate that the signal changes to neutral faces in the amygdala and SI with respect to condition (multiple or single faces) and stimulus order may relate to the involvement of these structures in novelty detection and the orienting response.

A magnetic resonance imaging study of cortical thickness in animal phobia.

BACKGROUND: Despite the high prevalence of specific phobia (SP), its neural substrates remain undetermined. Although an initial series of functional neuroimaging studies have implicated paralimbic and sensory cortical regions in the pathophysiology of SP, to date contemporary morphometric neuroimaging methods have not been applied to test specific hypotheses regarding structural abnormalities. METHODS: Morphometric magnetic resonance imaging (MRI) methods were used to measure regional cortical thickness in 10 subjects with SP (animal type) and 20 healthy comparison (HC) subjects. RESULTS: Consistent with a priori hypotheses, between-group differences in cortical thickness were found within paralimbic and sensory cortical regions. Specifically, in comparison with the HC group, the SP group exhibited increased cortical thickness in bilateral insular, bilateral pregenual anterior cingulate, and bilateral posterior cingulate cortex as well as left visual cortical regions. CONCLUSIONS: Taken together, these structural findings parallel results from initial functional imaging studies that implicate paralimbic and sensory cortical regions in the mediating anatomy of SP symptoms. Further research will be necessary to replicate these findings and to determine their specificity as well as their pathophysiologic significance.