Elana Harris

Disinhibition as a side effect of treatment with fluvoxamine in pediatric patients with obsessive-compulsive disorder.

Selective serotonin reuptake inhibitors (SSRIs) are usually well tolerated in the pediatric population, and widely used in the treatment of obsessive-compulsive disorder (OCD). Of the 51 pediatric patients with obsessive-compulsive disorder seen in our outpatient clinic between January 2009 and July 2009, 3 of them developed behavioral disinhibition after treatment with fluvoxamine. These cases are described and discussed in relation to the use of CYP2D6 and CYP2C19 pharmacogenetic testing in patients treated with serotonin-selective reuptake inhibitors.

Real-Time Functional Mapping with Electrocorticography in Pediatric Epilepsy Comparison with fMRI and ESM Findings

SIGFRIED (SIGnal modeling For Real-time Identification and Event Detection) software provides real-time functional mapping (RTFM) of eloquent cortex for epilepsy patients preparing to undergo resective surgery. This study presents the first application of paradigms used in functional magnetic resonance (fMRI) and electrical cortical stimulation mapping (ESM) studies for shared functional cortical mapping in the context of RTFM. Results from the 3 modalities are compared. A left-handed 13-year-old male with intractable epilepsy participated in functional mapping for localization of eloquent language cortex with fMRI, ESM, and RTFM. For RTFM, data were acquired over the frontal and temporal cortex. Several paradigms were sequentially presented: passive (listening to stories) and active (picture naming and verb generation). For verb generation and story processing, fMRI showed atypical right lateralizing language activation within temporal lobe regions of interest and bilateral frontal activation with slight right lateralization. Left hemisphere ESM demonstrated no eloquent language areas. RTFM procedures using story processing and picture naming elicited activity in the right lateral and basal temporal regions. Verb generation elicited strong right lateral temporal lobe activation, as well as left frontal lobe activation. RTFM results confirmed atypical language lateralization evident from fMRI and ESM. We demonstrated the feasibility and usefulness of a new RTFM stimulation paradigm during presurgical evaluation. Block design paradigms used in fMRI may be optimal for this purpose. Further development is needed to create age-appropriate RTFM test batteries.

Neural correlates associated with symptom provocation in pediatric obsessive compulsive disorder after a single session of sham-controlled repetitive transcranial magnetic stimulation.

Treatments for pediatric obsessive-compulsive disorder (OCD) could be enhanced if the physiological changes engendered by treatment were known. This study examined neural correlates of a provocation task in youth with OCD, before and after sham-controlled repetitive transcranial magnetic stimulation (rTMS). We hypothesized that rTMS to the right dorsolateral prefrontal cortex would inhibit activity in cortico-striato-thalamic (CST) circuits associated with OCD to a greater extent than sham rTMS. After baseline (Time 1) functional magnetic resonance imaging (fMRI) during a provocation task, subjects received one session of either fMRI-guided sham (SG; n=8) or active (AG; n=10) 1-Hz rTMS over the rDLPFC for 30min. During rTMS, subjects were presented with personalized images that evoked OCD-related anxiety. Following stimulation, fMRI and the provocation task were repeated (Time 2). Contrary to our prediction for the provocation task, the AG was associated with no changes in BOLD response from Times 1 to 2. In contrast, the SG had a significant increase at Time 2 in BOLD response in the right inferior frontal gyrus and right putamen, which persisted after adjusting for age, gender, and time to scanner as covariates. This study provides an initial framework for TMS interrogation of the CST circuit in pediatric OCD.

Real-Time Functional Mapping With Electrocorticography in Pediatric Epilepsy

SIGFRIED (SIGnal modeling For Real-time Identification and Event Detection) software provides real-time functional mapping (RTFM) of eloquent cortex for epilepsy patients preparing to undergo resective surgery. This study presents the first application of paradigms used in functional magnetic resonance (fMRI) and electrical cortical stimulation mapping (ESM) studies for shared functional cortical mapping in the context of RTFM. Results from the 3 modalities are compared. A left-handed 13-year-old male with intractable epilepsy participated in functional mapping for localization of eloquent language cortex with fMRI, ESM, and RTFM. For RTFM, data were acquired over the frontal and temporal cortex. Several paradigms were sequentially presented: passive (listening to stories) and active (picture naming and verb generation). For verb generation and story processing, fMRI showed atypical right lateralizing language activation within temporal lobe regions of interest and bilateral frontal activation with slight right lateralization. Left hemisphere ESM demonstrated no eloquent language areas. RTFM procedures using story processing and picture naming elicited activity in the right lateral and basal temporal regions. Verb generation elicited strong right lateral temporal lobe activation, as well as left frontal lobe activation. RTFM results confirmed atypical language lateralization evident from fMRI and ESM. We demonstrated the feasibility and usefulness of a new RTFM stimulation paradigm during presurgical evaluation. Block design paradigms used in fMRI may be optimal for this purpose. Further development is needed to create age-appropriate RTFM test batteries.

Tic Suppression: The Medical Model

Tics are intermittent, repetitive, patterned but usually nonrhythmic motor movements or sounds performed in response to urges or involuntarily. They are the cardinal symptom required for a DSM-IV-TR diagnosis of Tourettes disorder (TD). Many children with TD present with mild tics that cause no significant impairment. However, when tics cause pain or interference, medical treatment is reasonable. This article reviews current evidence for treatment of tics in TD with medications as well as deep brain stimulation and transcranial magnetic stimulation. It concludes with some context for understanding this literature, relevant to treatment decisions and future treatment research in TD.

Magnetoencephalography reveals altered auditory information processing in youth with obsessive-compulsive disorder

Patients with obsessive-compulsive disorder (OCD) often report sensory intolerances which may lead to significant functional impairment. This study used auditory evoked fields (AEFs) to address the question of whether neural correlates of sensory auditory information processing differ in youth with OCD compared with healthy comparison subjects (HCS). AEFs, recorded with a whole head 275-channel magnetoencephalography system, were elicited in response to binaural auditory stimuli from 10 pediatric subjects with OCD (ages 8-13, mean 11 years, 6 males) and 10 age- and gender-matched HCS. Three major neuromagnetic responses were studied: M70 (60-80 ms), M100 (90-120 ms), and M150 (130-190 ms). When compared with HCS, subjects with OCD demonstrated delayed latency of the M100 response. In subjects with OCD the amplitude of the M100 and M150 responses was significantly greater in the right hemisphere compared with the left hemisphere. Current results suggest that when compared with HCS, subjects with OCD have altered auditory information processing, evident from the delayed latency of the M100 response, which is thought to be associated with the encoding of physical stimulus characteristics. Interhemispheric asymmetry with increased M100 and M150 amplitudes over the right hemisphere compared with the left hemisphere was found in young OCD subjects. These results should be interpreted with caution due to the high variability rate of responses in both HCS and OCD subjects, as well as the possible effect of medication in OCD subjects.

The Utility of Electromagnetic Activity Measures in Obsessive Compulsive Disorder and Schizophrenia

A young adult presents to a psychiatrist and describes the need to “unwind” himself around pieces of furniture if he has passed them in a clockwise direction. When he is weighed, he expresses the concern that pieces of rubber will come off the office scale and that will be considered stealing. He hesitates before he sits down on a chair in the office because he is afraid that he will catch the emotional problems of the person who sat in the chair before him. Are these psychotic delusions or obsessions and compulsions?

The Frequency Profile of Somatosensory Evoked Magnetic Fields in the Developing Brain

The objective of this paper is to study the variations of magnetic fields evoked by index finger stimulation in four age groups (6-9, 10-13, 14-17 and 18-49 years old) of normal population. We recorded magnetic fields during unilateral electrical stimulation of the index finger in 60 healthy children (7±1.2, 12±1.3 and 15±1.1) and 20 healthy adults (30±5.7) using a 275-channel whole head magnetoencephalography (MEG) system. Each group consisted of 10 females and males. Electrical stimulation was applied in randomized order to the right or left index finger with two digital rings. One hundred trials were recorded for both the right and left index finger stimulations. MEG data were analyzed in both the time and frequency domains. Brain regions associated with finger stimulations were localized with the equivalent current dipoles (ECDs). Time-frequency analysis was at the source level with a vector beamformer and Morlet wavelets. Our data have revealed evoked neuromagnetic signals in low-frequency ranges (10-40 Hz). In addition, the spectrograms revealed consistent focal increases of spectral power around 120-200 Hz in the left and right hemispheres in children. Furthermore, the neuromagnetic activation above 200 Hz was also observed, which were in the frequency range of 600-890 Hz. The preliminary data suggest that neuromagnetic signals above 120 Hz in the developing brain are noninvasive detectable.