Evoked Potentials Investigations of Deficit Versus Nondeficit Schizophrenia: EEG-MEG Preliminary Data.

Heterogeneity of schizophrenia is a major obstacle toward understanding the disorder. One likely subtype is the deficit syndrome (DS) where patients suffer from predominantly negative symptoms. This study investigated the evoked responses and the evoked magnetic fields to identify the neurophysiological deviations associated with the DS. Ten subjects were recruited for each group (Control, DS, and Nondeficit schizophrenia [NDS]). Subjects underwent magnetoencephalography (MEG) and electroencephalography (EEG) testing while listening to an oddball paradigm to generate the P300 as well as a paired click paradigm to generate the mid-latency auditory-evoked responses (MLAER) in a sensory gating paradigm. MEG-coherence source imaging (CSI) during P300 task revealed a significantly higher average coherence value in DS than NDS subjects in the gamma band (30-80 Hz), when listening to standard stimuli but only NDS subjects had a higher average coherence level in the gamma band than controls when listening to the novel sounds. P50, N100, and P3a ERP amplitudes (EEG analysis) were significantly decreased in NDS compared with DS subjects. The data suggest that the deviations in the 2 patient groups are qualitatively different. Deviances in NDS patients suggest difficulty in both early (as in the gating paradigm), as well as later top-down processes (P300 paradigm). The main deviation in the DS group was an exaggerated responsiveness to ongoing irrelevant stimuli detected by EEG whereas NDS subjects had an exaggerated response to novelty.

Magnetoencephalography shows atypical sensitivity to linguistic sound sequences in autism spectrum disorder.

Neuroscientific evidence points toward atypical auditory processing in individuals with autism spectrum disorders (ASD), and yet, the consequences of this for receptive language remain unclear. Using magnetoencephalography and a passive listening task, we test for cascading effects on speech sound processing. Children with ASD and age-matched control participants (8-12 years old) listened to nonce linguistic stimuli that either did or did not conform to the phonological rules that govern consonant sequences in English (e.g. legal 'vimp' vs. illegal 'vimk'). Beamformer source analysis was used to isolate evoked responses (0.1-30 Hz) to these stimuli in the left and the right auditory cortex. Right auditory responses from participants with ASD, but not control participants, showed an attenuated response to illegal sequences relative to legal sequences that emerged around 330 ms after the onset of the critical phoneme. These results suggest that phonological processing is impacted in ASD, perhaps because of cascading effects from disrupted initial acoustic processing.

Multimodal imaging of temporal processing in typical and atypical language development.

New approaches to understanding language and reading acquisition propose that the human brain's ability to synchronize its neural firing rate to syllable-length linguistic units may be important to children's ability to acquire human language. Yet, little evidence from brain imaging studies has been available to support this proposal. Here, we summarize three recent brain imaging (functional near-infrared spectroscopy (fNIRS), functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG)) studies from our laboratories with young English-speaking children (aged 6-12 years). In the first study (fNIRS), we used an auditory beat perception task to show that, in children, the left superior temporal gyrus (STG) responds preferentially to rhythmic beats at 1.5 Hz. In the second study (fMRI), we found correlations between children's amplitude rise-time sensitivity, phonological awareness, and brain activation in the left STG. In the third study (MEG), typically developing children outperformed children with autism spectrum disorder in extracting words from rhythmically rich foreign speech and displayed different brain activation during the learning phase. The overall findings suggest that the efficiency with which left temporal regions process slow temporal (rhythmic) information may be important for gains in language and reading proficiency. These findings carry implications for better understanding of the brain's mechanisms that support language and reading acquisition during both typical and atypical development.

Evidence for a frontal cortex role in both auditory and somatosensory habituation: a MEG study.

Auditory and somatosensory responses to paired stimuli were investigated for commonality of frontal activation that may be associated with gating using magnetoencephalography (MEG). A paired stimulus paradigm for each sensory evoked study tested right and left hemispheres independently in ten normal controls. MR-FOCUSS, a current density technique, imaged simultaneously active cortical sources. Each subject showed source localization, in the primary auditory or somatosensory cortex, for the respective stimuli following both the first (S1) and second (S2) impulses. Gating ratios for the auditory M50 response, equivalent to the P50 in EEG, were 0.54+/-0.24 and 0.63+/-0.52 for the right and left hemispheres. Somatosensory gating ratios were evaluated for early and late latencies as the pulse duration elicits extended response. Early gating ratios for right and left hemispheres were 0.69+/-0.21 and 0.69+/-0.41 while late ratios were 0.81+/-0.41 and 0.80+/-0.48. Regions of activation in the frontal cortex, beyond the primary auditory or somatosensory cortex, were mapped within 25 ms of peak S1 latencies in 9/10 subjects during auditory stimulus and in 10/10 subjects for somatosensory stimulus. Similar frontal activations were mapped within 25 ms of peak S2 latencies for 75% of auditory responses and for 100% of somatosensory responses. Comparison between modalities showed similar frontal region activations for 17/20 S1 responses and for 13/20 S2 responses. MEG offers a technique for evaluating cross modality gating. The results suggest similar frontal sources are simultaneously active during auditory and somatosensory habituation.

Direct electrical stimulation of Heschl's gyrus for tinnitus treatment.

OBJECTIVES/HYPOTHESIS: The purpose of the study was to determine the effect of electrical stimulation of the auditory cortex in patients with tinnitus. STUDY DESIGN: Nonrandomized clinical trial. METHODS: Two patients with debilitating tinnitus refractory to conventional therapies were treated. Patients were evaluated with validated questionnaires and psychoacoustic measures to determine the frequency and pitch of their tinnitus. Tones at these frequencies were then presented to the first patient (RP) under magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) to determine the tonotopic map for these frequencies in Heschl's gyrus. These tonotopic sites were targeted for implant with a quadripolar electrode. In the second patient (MV), only the fMRI tonotopic map was performed. These fMRI results detected an area of increased activity, which was selected as the site for the implanted bipolar electrode. RESULTS: Patient RP (bilateral tinnitus for 2 years) has experienced a sustained reduction to near elimination of tinnitus with intracerebral implanted electrodes, whereas patient MV (unilateral tinnitus for 7 years) had an unsustained reduction in her tinnitus. CONCLUSION: These findings suggest that the perception and annoyance of tinnitus may be modulated or reduced through electrical stimulation of the auditory cortex. These unsustained effects for patient MV may have been influenced by the longstanding nature of her tinnitus or by another reason as yet undetermined.

Recovery in a patient with locked-in syndrome.

BACKGROUND AND PURPOSE: Sildenafil citrate has been shown to enhance neurogenesis, angiogenesis, synaptogenesis, and neurological outcome by augmentation of cyclic guanosine monophosphate (cGMP) levels in animal models of ischemic stroke. Whether sildenafil citrate may be helpful for recovery in human stroke is unknown at this time. METHODS: A 41-year-old woman with locked-in syndrome due to pontine infarction began receiving 150 mg of oral sildenafil citrate daily on a compassionate use basis in August 2003 and continues treatment at this time. Magneto-encephalography (MEG) was performed at 12 and 17 months after stroke. RESULTS: No serious adverse events have occurred. Significant milestone recoveries including standing, use of both arms, talking, and full return of swallowing have occurred, particularly after nine months of treatment. The MEG showed a significantly increased amplitude in the somatosensory cortex. CONCLUSION: Daily use of high dose sildenafil citrate appears to be safe in this patient with stroke resulting in locked-in syndrome. Further studies will be required to establish safety and efficacy.