Frank Bihari

Analysis of 22 kHz ultrasonic vocalization in laboratory rats : long and short calls

There is a remarkable variation in the length of single ultrasonic calls emitted by adult rats. The duration of calls is likely to convey information for conspecifics. The goal of the present study was to analyze 22 kHz calls emitted by naive laboratory rats in response to contact with the human hand and to measure their acoustic features, with a particular emphasis on call duration. Repeated hand touch applied to the nape of the neck of rats induced ultrasonic calls, 97.4% of which were within the range of 20-29 kHz and 2.6% of which were within 44-67 kHz. Distribution of duration of 6765 calls revealed two subpopulations of 22 kHz calls: 20-300 ms calls with its peak at 150 ms and calls above 310 ms with highest values at approximately 500-600 ms without a clear peak. These two call populations were referred to as short and long calls, respectively. The short and the long vocalizations contained 80% and 100% of calls within the range of the 22 kHz frequency, respectively. The findings indicated that, in the situation studied, the 22 kHz vocalization of adult rats consists of two distinguishable subpopulation of calls: short and long with the boundary between them at 300 ms.

Ultrasonic vocalization in rats produced by cholinergic stimulation of the brain

Neurotransmitters involved in production of ultrasounds in rodents have not yet been identified. It is also not known whether brain mechanisms regulating production of ultrasounds and audible sounds are similar or different. The present study provides the first report that intracerebral injection of an acetylcholine agonist, carbachol, in rats induces ultrasonic vocalization. Since the same agent can induce audible vocalization in cats, the finding suggests a possible common neurochemical substrate underlying production of sonic and ultrasonic vocalization in mammals. The data accumulated to date indicate also that these two kinds of vocalization may play a homologous role in animal communication.

Linear aspects of transformation from interictal epileptic discharges to BOLD fMRI signals in an animal model of occipital epilepsy

Epileptic disorders manifest with seizures and interictal epileptic discharges (IEDs). The hemodynamic changes that accompany IEDs are poorly understood and may be critical for understanding epileptogenesis. Despite a known linear coupling of the neurovascular elements in normal brain tissues, previous simultaneous electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) studies have shown variable correlations between epileptic discharges and blood oxygenation level-dependent (BOLD) response, partly because most previous studies assumed particular hemodynamic properties in normal brain tissue. The occurrence of IEDs in human subjects is unpredictable. Therefore, an animal model with reproducible stereotyped IEDs was developed by the focal injection of penicillin into the right occipital cortex of rats anesthetized with isoflurane. Simultaneous EEG-fMRI was used to study the hemodynamic changes during IEDs. A hybrid of temporal independent component analysis (ICA) of EEG and spatial ICA of fMRI data was used to correlate BOLD fMRI signals with IEDs. A linear autoregression with exogenous input (ARX) model was used to estimate the hemodynamic impulse response function (HIRF) based on the data from simultaneous EEG-fMRI measurement. Changes in the measured BOLD signal from the right primary visual cortex and bilateral visual association cortices were consistently coupled to IEDs. The linear ARX model was applied here to confirm that a linear transform can be used to study the correlation between BOLD signal and its corresponding neural activity in this animal model of occipital epilepsy.

Functional MRI study of the primary somatosensory cortex in comatose survivors of cardiac arrest

It is difficult to assess cerebral function in comatose patients. Because earlier functional neuroimaging studies demonstrate associations between cerebral metabolism and levels of consciousness, fMRI in comatose survivors of cardiac arrest could provide further insight into cerebral function during coma. Using fMRI, cerebral activation to somatosensory stimulation to the palm of the hand was measured in 19 comatose survivors of cardiac arrest and in 10 healthy control subjects and was compared to somatosensory-evoked potential (SSEP) testing of the median nerve. Changes in the blood oxygenation-level dependent signal (BOLD) in the primary somatosensory cortex (S1) contralateral to the stimulated hand were quantified. Clinical outcome was assessed using the Glasgow Outcome Scale (GOS) and the modified Rankin Scale at 3 months post-cardiac arrest. Five out of 19 patients were alive at 3 months. Patients who survived cardiac arrest showed greater BOLD in S1 contralateral to somatosensory stimulation of the hand compared to patients who eventually did not. Greater BOLD was also seen in S1 of patients who retained their SSEP N20 waveforms. There were also positive correlations between BOLD in S1 with both levels of consciousness and measures of outcome at 3 months. In summary, this study demonstrates that BOLD in the S1 contralateral to somatosensory stimulation of the hand varies with clinical measures of the level of consciousness during coma.

Real‐time display of artifact‐free electroencephalography during functional magnetic resonance imaging and magnetic resonance spectroscopy in an animal model of epilepsy

Simultaneous recording of electroencephalogram (EEG) and functional MRI (fMRI) or MR spectroscopy (MRS) can provide further insight into our understanding of the underlying mechanisms of neurologic disorders. Current technology for simultaneous EEG and MRI recording is limited by extensive postacquisition processing of the data. Real‐time display of artifact‐free EEG recording during fMRI/MRS studies is essential in studies that involve epilepsy to ensure that they address specific EEG features such as epileptic spikes or seizures. By optimizing the EEG recording equipment to maximize the common mode rejection ratio of its amplifiers, a unique EEG system was designed and tested that allowed real‐time display of the artifact‐free EEG during fMRI/MRS in an animal model of epilepsy. Spike recordings were optimized by suppression of the background EEG activity using fast‐acting and easily controlled inhalational anesthesia. Artifact suppression efficiency of 70–100% was achieved following direct subtraction of referentially recorded filtered EEG tracings from active electrodes, which were located in close proximity to each other (over homologous occipital cortices) and a reference electrode. Two independent postacquisition processing tools, independent component analysis and direct subtraction of unfiltered digital EEG data in MATLAB, were used to verify the accuracy of real‐time EEG display. Magn Reson Med 53:456–464, 2005.

Physiological monitoring of small animals during magnetic resonance imaging

Maintaining a stable physiologic state is essential when studying animal models of epilepsy with simultaneous electroencephalograph (EEG) and functional magnetic resonance imaging (fMRI) or EEG and magnetic resonance spectroscopy (MRS). To achieve and maintain such stability in rats in the MRI environment, a minimally invasive but comprehensive system was developed to monitor body temperature, heart rate, blood pressure, blood oxygen saturation and end-tidal CO2 (ETCO2) of expired gas. All physiologic parameters were successfully monitored in Sprague-Dawley rats without interfering with EEG recordings during simultaneous fMRI and MRS studies. Body temperature, heart rate, blood pressure, blood oxygen saturation, and ETCO2, were maintained between 36.5 and 37.5 degrees C, 250-450 beats/min, 136+/-17 mmHg, >90%, and 20-35 mmHg, respectively for 6-8 h under inhalational anesthesia. This set-up could be extended to study in vivo applications in other laboratory animals with only minor modifications.

Response of neurons of the rat anterior hypothalamic-preoptic area to carbachol.

Behavioural effects of carbachol given into the hypothalamic/preoptic area have been demonstrated but there is a paucity of information about the response of single neurons to carbachol. The aim of the present study was to determine the response of spontaneously firing neurons in the rat hypothalamic/preoptic area to application of carbachol by iontophoresis or by pressure injection in a dose and volume comparable with that used in behavioural studies. Extracellular single unit recordings showed a significant decrease in mean firing rate in 82% of neurons responding to iontophoretic carbachol and in 75.5% of neurons responding to carbachol injected about 600 microns away. An increase in firing rate occurred in only 15 and 17.6% of neurons, respectively. Application of saline did not alter the mean firing rate while application of glutamate into the same areas or ejection into the vicinity of the same neurons caused an increase in mean firing rate in 94% of responding neurons. The results indicate that a decrease in mean firing rate is the predominant neuronal response to carbachol in the anteromedial hypothalamic/preoptic area of the rat and we suggest that this decrease may be associated with behavioural responses to carbachol.

Memory loss and memory reorganization patterns in temporal lobe epilepsy patients undergoing anterior temporal lobe resection, as demonstrated by pre-versus post-operative functional MRI

This study was aimed to longitudinally assess memory function and whole-brain memory circuit reorganization in patients with temporal lobe epilepsy (TLE) by comparing activation potentials before versus after anterior temporal lobe (ATL) resection. Nineteen patients with medically-intractable TLE (10 left TLE, 9 right TLE) and 15 healthy controls were enrolled. Group analyses were conducted pre- and post-ATL of a novelty complex scene-encoding paradigm comparing areas of blood oxygen-level-dependent (BOLD) signal activations on functional magnetic resonance imaging (fMRI). None of the pre-operative patient characteristics we studied predicted the extent of pre- to post-operative memory loss. On fMRI, extra-temporal activations were detected pre-operatively in both LTLE and RTLE, particularly in the frontal lobe. Greater activations also were noted in the contralateral hippocampus and parahippocampus in both groups. Performing within-subject comparisons, post-op relative to pre-op, pronounced ipsilateral activations were identified in the left parahippocampal gyrus in LTLE, versus the right middle temporal gyrus in RTLE patients. Memory function was impaired pre-operatively but declined after ATL resection in both RTLE and LTLE patients. Post-operative fMRI results indicate possible functional adaptations to ATL loss, primarily occurring within the left parahippocampal gyrus versus right middle temporal gyrus in LTLE versus RTLE patients, respectively.