The Influence of Motoric Maneuvers on Cervical Vestibular Evoked Myogenic Potentials (cVEMPs).

BACKGROUND: The cervical vestibular evoked myogenic potential (cVEMP) is a vestibular response that is produced by the saccule in response to intense, often low-frequency, short-duration auditory stimuli, and is typically recorded from a contracted sternocleidomastoid (SCM) muscle. Previous research has shown that the amplitude of the cVEMP is related to the amount of SCM electromyographic (EMG) activity. PURPOSE: The aim of this study was to determine the influence of various remote motoric maneuvers on the amplitude of the cVEMP, as well as whether they influence the level of SCM EMG activity. RESEARCH DESIGN: The cVEMP was recorded from the left SCM muscle to left ear stimulation, in response to the SCM condition, as well as three different motoric maneuvers (jaw clench, eye closure, and the Jendrassik maneuver). EMG activity was also varied between 50, 75, and 100% of maximal EMG activity. STUDY SAMPLE: Data from 14 healthy subjects, with a mean age of 25.57 years (standard deviation = 5.93 years), was included in the present study. DATA COLLECTION AND ANALYSIS: Mean latency and amplitude of the cVEMP were compared across the four conditions and varying magnitudes of EMG contraction. SPSS 26 was used to statistically analyze the results. RESULTS: cVEMP latency did not vary across condition. cVEMP amplitude decreased with decreasing EMG magnitude. SCM contraction with jaw clench produced the largest increase in cVEMP amplitude; however, this condition was not significantly different from the SCM condition alone. SCM contraction with the Jendrassik maneuver produced a cVEMP amplitude that was similar and not statistically different from SCM contraction alone, and the addition of the eye closure maneuver to SCM contraction resulted in the lowest cVEMP amplitude, which was found to be statistically different from the standard SCM condition at 100 and 75% EMG activity. The amplitude relationship across the conditions was not found to vary with changes in EMG activity; however, a significant increase in EMG amplitude was found during the 50% muscle contraction condition when subjects performed the Jendrassik maneuver in addition to the standard SCM contraction. CONCLUSIONS: The addition of the eye closure maneuver to SCM contraction resulted in a significant decrease in cVEMP amplitude, while the addition of the Jendrassik maneuver resulted in a significant increase in EMG activity at the lowest level of SCM activation (i.e., 50%). Additional research is necessary to determine how motoric maneuvers influence the cVEMP amplitude, and whether the results are also dependent on how SCM contraction is being produced (e.g., while supine vs. sitting).

Attenuated Tonic and Enhanced Phasic Release of Dopamine in Attention Deficit Hyperactivity Disorder.

It is unclear whether attention deficit hyperactive disorder (ADHD) is a hypodopaminergic or hyperdopaminergic condition. Different sets of data suggest either hyperactive or hypoactive dopamine system. Since indirect methods used in earlier studies have arrived at contradictory conclusions, we directly measured the tonic and phasic release of dopamine in ADHD volunteers. The tonic release in ADHD and healthy control volunteers was measured and compared using dynamic molecular imaging technique. The phasic release during performance of Eriksen's flanker task was measured in the two groups using single scan dynamic molecular imaging technique. In these experiments volunteers were positioned in a positron emission tomography (PET) camera and administered a dopamine receptor ligand (11)C-raclopride intravenously. After the injection PET data were acquired dynamically while volunteers either stayed still (tonic release experiments) or performed the flanker task (phasic release experiments). PET data were analyzed to measure dynamic changes in ligand binding potential (BP) and other receptor kinetic parameters. The analysis revealed that at rest the ligand BP was significantly higher in the right caudate of ADHD volunteers suggesting reduced tonic release. During task performance significantly lower ligand BP was observed in the same area, indicating increased phasic release. In ADHD tonic release of dopamine is attenuated and the phasic release is enhanced in the right caudate. By characterizing the nature of dysregulated dopamine neurotransmission in ADHD, the results explain earlier findings of reduced or increased dopaminergic activity.

Masked smoothing using separable kernels for CT perfusion images.

BACKGROUND: CT perfusion images have a high contrast ratio between voxels representing different anatomy, such as tissue or vessels, which makes image segmentation of tissue and vascular regions relatively easy. However, grey and white matter tissue regions have relatively low values and can suffer from poor signal to noise ratios. While smoothing can improve the image quality of the tissue regions, the inclusion of much higher valued vascular voxels can skew the tissue values. It is thus desirable to smooth tissue voxels separately from other voxel types, as has been previously implemented using mean filter kernels. We created a novel Masked Smoothing method that performs Gaussian smoothing restricted to tissue voxels. Unlike previous methods, it is implemented as a combination of separable kernels and is therefore fast enough to consider for clinical work, even for large kernel sizes. METHODS: We compare our Masked Smoothing method to alternatives using Gaussian smoothing on an unaltered image volume and Gaussian smoothing on an image volume with vascular voxels set to zero. Each method was tested on simulation data, collected phantom data, and CT perfusion data sets. We then examined tissue voxels for bias and noise reduction. RESULTS: Simulation and phantom experiments demonstrate that Masked Smoothing does not bias the underlying tissue value, whereas the other smoothing methods create significant bias. Furthermore, using actual CT perfusion data, we demonstrate significant differences in the calculated CBF and CBV values dependent on the smoothing method used. CONCLUSION: The Masked Smoothing is fast enough to allow eventual clinical usage and can remove the bias of tissue voxel values that neighbor blood vessels. Conversely, the other Gaussian smoothing methods introduced significant bias to the tissue voxels.

Attenuation of regional cerebral blood flow during memory processing after coronary artery bypass surgery.

Reports of memory impairment after cardiac surgery are controversial. To address this controversy, we used positron emission tomography to examine changes in regional cerebral blood flow (rCBF) during memory processing before and after elective coronary artery bypass grafting surgery. In postoperative scans, we observed significantly reduced rCBF in 2 of the most important memory processing areas: the medial temporal lobe (P = 0.023) and the prefrontal cortex (P = 0.002). The results suggest postoperative attenuation of rCBF in brain areas involved in memory processing. These reductions could be used to evaluate severity of memory impairment after coronary artery bypass grafting surgery in patients at risk.

Masking level differences--a diffusion tensor imaging and functional MRI study.

In our previous study we investigated Masking Level Differences (MLD) using functional Magnetic Resonance Imaging (fMRI), but were unable to confirm neural correlations for the MLD within the auditory cortex and inferior colliculus. Here we have duplicated conditions from our previous study, but have included more participants and changed the study site to a new location with a newer scanner and presentation system. Additionally, Diffusion Tensor Imaging (DTI) is included to allow investigation of fiber tracts that may be involved with MLDs. Twenty participants were included and underwent audiometric testing and MRI scanning. The current study revealed regions of increased and decreased activity within the auditory cortex when comparing the combined noise and signal of the dichotic MLD stimuli (N0Sπ and NπS0) with N0S0. Furthermore, we found evidence of inferior colliculus involvement. Our DTI findings show strong correlations between DTI measures within the brainstem and signal detection threshold levels. Patterns of correlation when the signal was presented only to the right ear showed an extensive network in the left hemisphere; however, the opposite was not true for the signal presented only to the left ear. Our current study was able to confirm what we had previously hypothesized using fMRI, while extending our investigation of MLDs to include the characteristics of connecting neural pathways.

Improved operator agreement and efficiency using the minimum area contour change method for delineation of hyperintense multiple sclerosis lesions on FLAIR MRI.

BACKGROUND: Activity of disease in patients with multiple sclerosis (MS) is monitored by detecting and delineating hyper-intense lesions on MRI scans. The Minimum Area Contour Change (MACC) algorithm has been created with two main goals: a) to improve inter-operator agreement on outlining regions of interest (ROIs) and b) to automatically propagate longitudinal ROIs from the baseline scan to a follow-up scan. METHODS: The MACC algorithm first identifies an outer bound for the solution path, forms a high number of iso-contour curves based on equally spaced contour values, and then selects the best contour value to outline the lesion. The MACC software was tested on a set of 17 FLAIR MRI images evaluated by a pair of human experts and a longitudinal dataset of 12 pairs of T2-weighted Fluid Attenuated Inversion Recovery (FLAIR) images that had lesion analysis ROIs drawn by a single expert operator. RESULTS: In the tests where two human experts evaluated the same MRI images, the MACC program demonstrated that it could markedly reduce inter-operator outline error. In the longitudinal part of the study, the MACC program created ROIs on follow-up scans that were in close agreement to the original expert's ROIs. Finally, in a post-hoc analysis of 424 follow-up scans 91% of propagated MACC were accepted by an expert and only 9% of the final accepted ROIS had to be created or edited by the expert. CONCLUSION: When used with an expert operator's verification of automatically created ROIs, MACC can be used to improve inter- operator agreement and decrease analysis time, which should improve data collected and analyzed in multicenter clinical trials.

Correlation of cognition and SPECT perfusion: easy Z score and SPM analysis of a pilot sample with cerebral small vessel disease.

BACKGROUND/AIMS: To associate neuropsychology test performance with perfusion on single-photon emission computed tomography (SPECT) among 12 patients with cerebral small vessel disease. METHODS: The easy Z score imaging system (eZIS) was used to compare patient images to those of normal controls. Scores from neuropsychological tests commonly used to screen for dementia were associated with SPECT resting perfusion image values using the statistical parametric mapping (SPM) program. RESULTS: Immediate Memory and Delayed Memory index scores, as well as memory subtests of the Repeatable Battery for Assessment of Neuropsychological Status showed cluster- and voxelwise positive correlations with hypoperfusion in frontal, temporal and cerebellar regions. Negative correlations, primarily in frontal regions, were interpreted as compensatory hyperperfusion. CONCLUSION: eZIS and SPM analyses of SPECT images showed perfusion correlations with neuropsychological tests with small vessel disease.

Exercise treatment for postconcussion syndrome: a pilot study of changes in functional magnetic resonance imaging activation, physiology, and symptoms.

PURPOSE: To compare functional magnetic resonance imaging (fMRI) activation patterns during a cognitive task, exercise capacity, and symptoms in postconcussion syndrome (PCS) patients who received exercise treatment (n = 4) with a PCS placebo stretching group (n = 4) and a healthy control group (n = 4). METHODS: Subjects completed a math processing task during fMRI and an exercise treadmill test before (time 1) and after approximately 12 weeks (time 2). Exercise subjects performed aerobic exercise at 80% of the heart rate (HR) attained on the treadmill test, 20 minutes per day with an HR monitor at home, 6 days per week. The program was modified as the HR for symptom exacerbation increased. RESULTS: At time 1, there was no difference in fMRI activation between the 2 PCS groups but healthy controls had significantly greater activation in the posterior cingulate gyrus, lingual gyrus, and cerebellum versus all PCS subjects (P < .05, corrected for multiple comparisons). At time 2, exercise PCS did not differ from healthy controls whereas placebo stretching PCS had significantly less activity in the cerebellum (P < .05 corrected) and in the anterior cingulate gyrus and thalamus (P < .001, uncorrected) versus healthy controls. At time 2, exercise PCS achieved a significantly greater exercise HR (P < .001) and had fewer symptoms (P < .0004) than placebo stretching PCS. Cognitive performance did not differ by group or time. CONCLUSIONS: Controlled aerobic exercise rehabilitation may help restore normal cerebral blood flow regulation, as indicated by fMRI activation, in PCS patients. The PCS symptoms may be related to abnormal cerebral blood flow regulation.

Neural correlates of tinnitus duration and distress: a positron emission tomography study.

Cerebral (18)F-deoxyglucose positron emission tomography (FDG-PET) has shown altered auditory pathway activity in tinnitus. However, the corresponding studies involved only small samples and analyses were restricted to the auditory cortex in most studies. Evidence is growing that also limbic, frontal, and parietal areas are involved in the pathophysiology of chronic tinnitus. These regions are considered to mediate perceptual, attentional, and emotional processes. Thus, the aim of the present study was the systematic evaluation of metabolic brain activity in a large sample of tinnitus patients. Ninety one patients with chronic tinnitus underwent FDG-PET. The effects of tinnitus severity (assessed by a tinnitus questionnaire score), duration and laterality were evaluated with statistical parametric mapping (SPM) in whole brain analyses. In addition, region of interest analyses were performed for primary auditory areas. Tinnitus duration correlated positively with brain metabolism in right inferior frontal, right ventro-medial prefrontal, and right posterior cingulate cortex. Tinnitus distress correlated positively with activation of left and right posterior inferior temporal gyrus as well as left and right posterior parahippocampal-hippocampal interface. Region of interest analysis demonstrated an overactivation of left in contrast to right Heschl's gyrus independently from tinnitus laterality and anatomical hemispheric differences. Tinnitus duration and distress were associated with areas involved in attentional and emotional processing. This is in line with recent findings indicating the relevance of higher order areas in the pathophysiology of tinnitus. Earlier results of asymmetric activation of the auditory cortices in tinnitus were confirmed, i.e., left-sided overactivation was found independently from tinnitus laterality.

Functional anatomy of the masking level difference, an fMRI study.

INTRODUCTION: Masking level differences (MLDs) are differences in the hearing threshold for the detection of a signal presented in a noise background, where either the phase of the signal or noise is reversed between ears. We use N0/Nπ to denote noise presented in-phase/out-of-phase between ears and S0/Sπ to denote a 500 Hz sine wave signal as in/out-of-phase. Signal detection level for the noise/signal combinations N0Sπ and NπS0 is typically 10-20 dB better than for N0S0. All combinations have the same spectrum, level, and duration of both the signal and the noise. METHODS: Ten participants (5 female), age: 22-43, with N0Sπ-N0S0 MLDs greater than 10 dB, were imaged using a sparse BOLD fMRI sequence, with a 9 second gap (1 second quiet preceding stimuli). Band-pass (400-600 Hz) noise and an enveloped signal (.25 second tone burst, 50% duty-cycle) were used to create the stimuli. Brain maps of statistically significant regions were formed from a second-level analysis using SPM5. RESULTS: The contrast NπS0- N0Sπ had significant regions of activation in the right pulvinar, corpus callosum, and insula bilaterally. The left inferior frontal gyrus had significant activation for contrasts N0Sπ-N0S0 and NπS0-N0S0. The contrast N0S0-N0Sπ revealed a region in the right insula, and the contrast N0S0-NπS0 had a region of significance in the left insula. CONCLUSION: Our results extend the view that the thalamus acts as a gating mechanism to enable dichotic listening, and suggest that MLD processing is accomplished through thalamic communication with the insula, which communicate across the corpus callosum to either enhance or diminish the binaural signal (depending on the MLD condition). The audibility improvement of the signal with both MLD conditions is likely reflected by activation in the left inferior frontal gyrus, a late stage in the what/where model of auditory processing.

Improved assessment of multiple sclerosis lesion segmentation agreement via detection and outline error estimates.

BACKGROUND: Presented is the method "Detection and Outline Error Estimates" (DOEE) for assessing rater agreement in the delineation of multiple sclerosis (MS) lesions. The DOEE method divides operator or rater assessment into two parts: 1) Detection Error (DE) -- rater agreement in detecting the same regions to mark, and 2) Outline Error (OE) -- agreement of the raters in outlining of the same lesion. METHODS: DE, OE and Similarity Index (SI) values were calculated for two raters tested on a set of 17 fluid-attenuated inversion-recovery (FLAIR) images of patients with MS. DE, OE, and SI values were tested for dependence with mean total area (MTA) of the raters' Region of Interests (ROIs). RESULTS: When correlated with MTA, neither DE (ρ = .056, p=.83) nor the ratio of OE to MTA (ρ = .23, p=.37), referred to as Outline Error Rate (OER), exhibited significant correlation. In contrast, SI is found to be strongly correlated with MTA (ρ = .75, p < .001). Furthermore, DE and OER values can be used to model the variation in SI with MTA. CONCLUSIONS: The DE and OER indices are proposed as a better method than SI for comparing rater agreement of ROIs, which also provide specific information for raters to improve their agreement.

Cine cerebrospinal fluid imaging in multiple sclerosis.

PURPOSE: To investigate cerebrospinal fluid (CSF) dynamics in the aqueduct of Sylvius in multiple sclerosis (MS) patients and healthy controls (HC) using cine phase contrast imaging. MATERIALS AND METHODS: In all, 67 MS patients (48 relapsing-remitting [RR] and 19 secondary-progressive [SP]), nine patients with clinically isolated syndrome (CIS), and 35 age- and sex-matched HC were examined. CSF flow and velocity measures were quantified using a semiautomated method and compared with clinical and magnetic resonance imaging (MRI) disease outcomes. RESULTS: Significantly decreased CSF net flow was detected in MS patients compared to HC (-3.7 vs. -7.1 µL/beat, P = 0.005). There was a trend for increased net positive flow between SP, RR, and CIS patients. Altered CSF flow and velocity measures were associated with more severe T1 and T2 lesion volumes, lateral and fourth ventricular volumes, and third ventricular width in MS and CIS patients (P < 0.01 for all). In CIS patients, conversion to clinically definite MS in the following year was related to decreased CSF net flow (P = 0.007). There was a trend between increased annual relapse rate and altered CSF flow/velocity measures in RRMS patients (P < 0.05). CONCLUSION: CSF flow dynamics are altered in MS patients. More severe clinical and MRI outcomes in RRMS and CIS patients relate to altered CSF flow and velocity measures.

Use of 64-channel electroencephalography to study neural otolith-evoked responses.

BACKGROUND: The vestibular evoked myogenic potential (VEMP) is a myogenic response that can be used clinically to evaluate the function of the saccule. However, to date, little is known about the thalamo-cortical representation of saccular activation. It is important to understand all aspects of the VEMP, as this test is currently used clinically in the evaluation of saccular function. PURPOSE: To identify the areas of the brain that are activated in response to stimuli used clinically to evoke the VEMP. RESEARCH DESIGN: Electroencephalography (EEG) recordings combined with current density analyses were used to identify the areas of the brain that are activated in response to stimuli presented above VEMP threshold (500 Hz, 120 dB peak SPL [pSPL] tone bursts), as compared to stimuli presented below VEMP threshold (90 dB pSPL, 500 Hz tone bursts). Ten subjects without any history of balance or hearing impairment participated in the study. RESULTS: The neural otolith-evoked responses (NOERs) recorded in response to stimuli presented below VEMP threshold were absent or smaller than NOERs that were recorded in response to stimuli presented above VEMP threshold. Subsequent analyses with source localization techniques, followed by statistical analysis with SPM5 (Statistical Parametric Mapping), revealed several areas that were activated in response to the 120 dB pSPL tone bursts. These areas included the primary visual cortex, the precuneus, the precentral gyrus, the medial temporal gyrus, and the superior temporal gyrus. CONCLUSIONS: The present study found a number of specific brain areas that may be activated by otolith stimulation. Given the findings and source localization techniques (which required limited input from the investigator as to where the sources are believed to be located in the brain) used in the present study as well as the similarity in findings between studies employing galvanic stimuli, fMRI (functional magnetic resonance imaging), and scalp-recorded potentials in response to VEMP-eliciting stimuli, our study provides additional evidence that these brain regions are activated in response to stimuli that can be used clinically to evoke the VEMP.

Signal abnormalities on 1.5 and 3 Tesla brain MRI in multiple sclerosis patients and healthy controls. A morphological and spatial quantitative comparison study.

Previous studies in patients with multiple sclerosis (MS) revealed increased lesion count and volume on 3 T compared to 1.5 T. Morphological and spatial lesion characteristics between 1.5 T and 3 T have not been examined. The aim of this study was to investigate the effect of changing from a 1.5 T to a 3 T MRI scanner on the number, volume and spatial distribution of signal abnormalities (SA) on brain MRI in a sample of MS patients and normal controls (NC), using pair- and voxel-wise comparison procedures. Forty-one (41) MS patients (32 relapsing-remitting and 9 secondary-progressive) and 38 NC were examined on both 1.5 T and 3 T within one week in random order. T2-weighted hyperintensities (T2H) and T1-weighted hypointensities (T1H) were outlined semiautomatically by two operators in a blinded fashion on 1.5 T and 3 T images. Spatial lesion distribution was assessed using T2 and T1 voxel-wise SA probability maps (SAPM). Pair-wise analysis examined the proportion of SA not simultaneously outlined on 1.5 T and 3 T. A posteriori unblinded analysis was conducted to examine the non-overlapping identifications of SA between the 1.5 T and 3 T. For pair-wise T2- and T1-analyses, a higher number and individual volume of SA were detected on 3 T compared to 1.5 T (p<0.0001) in both MS and NC. Logistic regression analysis showed that the likelihood of missing SA on 1.5 T was significantly higher for smaller SA in both MS and NC groups. SA probability map (SAPM) analysis revealed significantly more regionally distinct spatial SA differences on 3 T compared to 1.5 T in both groups (p<0.05); these were most pronounced in the occipital, periventricular and cortical regions for T2H. This study provides important information regarding morphological and spatial differences between data acquired using 1.5 T and 3 T protocols at the two scanner field strengths.

Multi-site phasic neural activity mediates the execution of an auditory continuous performance task: a PET and electrophysiological study.

BACKGROUND AND PURPOSE: We studied an auditory continuous performance task with positron emission tomography(PET) and EEG-derived current density reconstructions (CDRs) to define the spatial and temporal aspects of auditory attention. METHODS: The CDRs were employed to segregate responses to targets and non-targets at sites identified by PET. We then studied the time course of brain activity using statistical parametric mapping (SPM) of the CDR data. RESULTS: In contrast to target EEG activity, non-targets did not produce significant peaks after 300 ms. Pre-300 ms biphasic activation of auditory, left posterior frontal, left supplemental,and primary motor cortices and the anterior cingulate (AC) and biphasic suppression of posterior cingulate and occipital cortex were identical for targets and non-targets and may mediate the target non-target decision. SPM analysis of post-300 ms CDRs showed cingulate cortices were the first to be reactivated, remained active through 672 ms, and were accompanied by reactivation and deactivation of the same sites observed in the pre-P300 responses. CONCLUSIONS: The cingulate may play an important role in post-decisional activity and control activity at other sites involved in post-decisional cognitive processing.

Multi-site phasic neural activity mediates the execution of an auditory continuous performance task: a PET and electrophysiological study.

BACKGROUND AND PURPOSE: We studied an auditory continuous performance task with positron emission tomography (PET) and EEG-derived current density reconstructions (CDRs) to define the spatial and temporal aspects of auditory attention. METHODS: The CDRs were employed to segregate responses to targets and non-targets at sites identified by PET. We then studied the time course of brain activity using statistical parametric mapping (SPM) of the CDR data. RESULTS: In contrast to target EEG activity, non-targets did not produce significant peaks after 300 ms. Pre-300 ms biphasic activation of auditory, left posterior frontal, left supplemental, and primary motor cortices and the anterior cingulate (AC) and biphasic suppression of posterior cingulate and occipital cortex were identical for targets and non-targets and may mediate the target non-target decision. SPM analysis of post-300 ms CDRs showed cingulate cortices were the first to be reactivated, remained active through 672 ms, and were accompanied by reactivation and deactivation of the same sites observed in the pre-P300 responses. CONCLUSIONS: The cingulate may play an important role in post-decisional activity and control activity at other sites involved in post-decisional cognitive processing.

Cognitive therapy for irritable bowel syndrome is associated with reduced limbic activity, GI symptoms, and anxiety.

This study sought to identify brain regions that underlie symptom changes in severely affected IBS patients undergoing cognitive therapy (CT). Five healthy controls and 6 Rome II diagnosed IBS patients underwent psychological testing followed by rectal balloon distention while brain neural activity was measured with O-15 water positron emission tomography (PET) before and after a brief regimen of CT. Pre-treatment resting state scans, without distention, were compared to post-treatment scans using statistical parametric mapping (SPM). Neural activity in the parahippocampal gyrus and inferior portion of the right cortex cingulate were reduced in the post-treatment scan, compared to pre-treatment (x, y, z coordinates in MNI standard space were -30, -12, -30, P=0.017; 6, 34, -8, P=0.023, respectively). Blood flow values at these two sites in the controls were intermediate between those in the pre- and post-treatment IBS patients. Limbic activity changes were accompanied by significant improvements in GI symptoms (e.g., pain, bowel dysfunction) and psychological functioning (e.g., anxiety, worry). The left pons (-2, -26, -28, P=0.04) showed decreased neural activity which was correlated with post-treatment anxiety scores. Changes in neural activity of cortical-limbic regions that subserve hypervigilance and emotion regulation may represent biologically oriented change mechanisms that mediate symptom improvement of CT for IBS.

Mapping the 40-Hz auditory steady-state response using current density reconstructions.

We mapped the 40-Hz aSSR from nine normal subjects using PET-independent low-resolution electroencephalographic tomography (LORETA) as well as PET-weighted LORETA and minimum norm (MinNorm) current density reconstructions. In grand mean data, PET-independent LORETA identified seven sites with peaks in current density in right temporal lobe, right brainstem/cerebellum, right parietal lobe, left cerebellum/temporal lobe, and right frontal lobe. PET-weighted LORETA found six of the same sites as the PET-independent LORETA: the right brainstem source was eliminated and two right-frontal sources were added. Both LORETA analyses revealed considerable phase dispersion across identified sources. In both LORETA analyses, the relative time course of activation measured from an arbitrary starting phase progressed from right temporal lobe to right mid-frontal lobe to right parietal-frontal to right inferior parietal and finally to left cerebellum and left temporal lobe. MinNorm analysis incorporating PET information identified sources in the same locations as specified in the PET data. These sources were synchronized, with their amplitudes peaking almost simultaneously. Both PET-independent and PET-weighted LORETA results suggest that the aSSR is: (1) the result of a reverberating network with two or more groups of sources that recurrently excite each other or (2) the result of sequential auditory processing through various levels of a hierarchical network. In contrast, the PET-weighted MinNorm results suggest that the 40-Hz response represents simultaneous activation over widely spaced areas of the brain, perhaps due to synchronization of gamma-band activity to a common neural clock.

PET imaging of the 40 Hz auditory steady state response.

The auditory steady state response (aSSR) is an oscillatory electrical potential recorded from the scalp induced by amplitude-modulated (AM) or click/tone burst stimuli. Its clinical utility has been limited by uncertainty regarding the specific areas of the brain involved in its generation. To identify the generators of the aSSR, 15O-water PET imaging was used to locate the regions of the brain activated by a steady 1 kHz pure tone, the same tone amplitude modulated (AM) at 40 Hz and the specific regions of the brain responsive to the AM component of the stimulus relative to the continuous tone. The continuous tone produced four clusters of activation. The boundaries of these activated clusters extended to include regions in left primary auditory cortex, right non-primary auditory cortex, left thalamus, and left cingulate. The AM tone produced three clusters of activation. The boundaries of these activated clusters extended to include primary auditory cortex bilaterally, left medial geniculate and right middle frontal gyrus. Two regions were specifically responsive to the AM component of the stimulus. These activated clusters extended to include the right anterior cingulate near frontal cortex and right auditory cortex. We conclude that cortical sites, including areas outside primary auditory cortex, are involved in generating the aSSR. There was an unexpected difference between morning and afternoon session scans that may reflect a pre- versus post-prandial state. These results support the hypothesis that a distributed resonating circuit mediates the generation of the aSSR.