Effects of lasalocid and intermittent feeding of chlortetracycline on the growth of prepubertal dairy heifers.

Forty Holstein heifers entered the 12-wk study at approximately 12 wk of age. At enrollment, heifers were blocked by birth date and assigned to 1 of 4 treatments: (1) carrier (30 g; control); (2) lasalocid + carrier (1 mg/kg of body weight; L); (3) chlortetracycline + carrier (22 mg/kg of body weight; CTC); (4) L + CTC + carrier (CTCL). Heifers on CTC and CTCL were provided treatment Monday through Friday and carrier only on Saturday and Sunday. These heifers were provided their respective treatment during wk 1 to 4, 6, and 10; wk 5, 7 to 9, and 11 to 12 heifers were provided the nonmedicated carrier. Heifers were individually fed a total mixed ration with treatments top-dressed at 1200 h daily. Dry matter intake was monitored for each heifer and feed provided was adjusted according to individual intakes. Skeletal measurements were taken weekly and blood samples were obtained every Monday, Wednesday, and Friday. Blood samples were analyzed for thyroxine concentration via radial immunoassay. Heifers supplemented with L had lower average daily gain , overall body weight gain, and trends for lower daily body length gain and overall girth gain compared with CTC heifers, but similar to control and CTCL heifers. Heifers fed L had lower hip height gain and overall hip height gain compared with CTCL heifers, but similar to control and CTC heifers. Heifers fed L had lower overall withers height gain compared with control heifers, but similar to CTC and CTCL heifers. No treatment effect on thyroxine concentrations was observed. These data indicate that L did not increase growth. Results from this experiment indicate that supplementing heifers with L was not beneficial and no benefits to supplementing heifers with CTC or the combination of CTC and L were evident compared with control heifers. Heifers in this study experienced minimal health problems and were regarded to be under low stress levels. Supplementing CTC and L may be beneficial to growing heifers under conditions where disease exposure and stressors are greater.

Steady state and induced auditory gamma deficits in schizophrenia.

Steady state auditory evoked potentials (SSAEPs) in the electroencephalogram (EEG) and magnetoencephalogram (MEG) have been reported to be reduced in schizophrenia, most consistently to frequencies in the gamma range (40 Hz and greater). The current study evaluated the specificity of this deficit over a broad range of stimulus frequencies and harmonics, the relationship between phase locking and signal power, and whether induced 40 Hz activity was also affected. SSAEPs to amplitude modulated tones from 5 to 50 Hz were obtained from subjects with schizophrenia (SZ) and healthy control subjects in 5 Hz steps. Time-frequency spectral analysis was used to differentiate EEG activity synchronized in phase across trials using Phase Locking Factor (PLF) and Mean Power (MP) change from baseline activity. In the SSAEP frequency response condition, patients with SZ showed broad band reductions in both PLF and MP. In addition, the control subjects showed a more pronounced increase in PLF with increases in power compared to SZ subjects. A noise pulse embedded in 40 Hz stimuli resulted in a transient reduction of PLF and MP at 40 Hz in control subjects, while SZ showed diminished overall PLF. Finally, induced gamma (around 40 Hz) response to unmodulated tone stimuli was also reduced in SZ, indicating that disturbances in this oscillatory activity are not confined to SSAEPs. In summary, SZ subjects show impaired oscillatory responses in the gamma range across a wide variety of experimental conditions. Reduction of PLF along with reduced MP may reflect abnormalities in the auditory cortical circuits, such as a reduction in pyramidal cell volume, spine density and alterations in GABAergic neurons.

Gamma frequency-range abnormalities to auditory stimulation in schizophrenia.

BACKGROUND: Basic science studies at the neuronal systems level have indicated that gamma-range (30-50 Hz) neural synchronization may be a key mechanism of information processing in neural networks, reflecting integration of various features of an object. Furthermore, gamma-range synchronization is thought to depend on the glutamatergically mediated interplay between excitatory projection neurons and inhibitory neurons utilizing gamma-aminobutyric acid (GABA), which postmortem studies suggest may be abnormal in schizophrenia. We therefore tested whether auditory neural networks in patients with schizophrenia could support gamma-range synchronization. METHODS: Synchronization of the electroencephalogram (EEG) to different rates (20-40 Hz) of auditory stimulation was recorded from 15 patients with schizophrenia and 15 sex-, age-, and handedness-matched control subjects. The EEG power at each stimulation frequency was compared between groups. The time course of the phase relationship between each stimulus and EEG peak was also evaluated for gamma-range (40 Hz) stimulation. RESULTS: Schizophrenic patients showed reduced EEG power at 40 Hz, but not at lower frequencies of stimulation. In addition, schizophrenic patients showed delayed onset of phase synchronization and delayed desynchronization to the click train. CONCLUSIONS: These data provide new information on selective deficits in early-stage sensory processing in schizophrenia, a failure to support the entrainment of intrinsic gamma-frequency oscillators. The reduced EEG power at 40 Hz in schizophrenic patients may reflect a dysfunction of the recurrent inhibitory drive on auditory neural networks.

Auditory mismatch negativity in schizophrenia: topographic evaluation with a high-density recording montage.

OBJECTIVE: The mismatch negativity, a negative component in the auditory event-related potential, is thought to index automatic processes involved in sensory or echoic memory. The authors' goal in this study was to examine the topography of auditory mismatch negativity in schizophrenia with a high-density, 64-channel recording montage. METHOD: Mismatch negativity topography was evaluated in 23 right-handed male patients with schizophrenia who were receiving medication and in 23 nonschizophrenic comparison subjects who were matched in age, handedness, and parental socioeconomic status. The Positive and Negative Syndrome Scale was used to measure psychiatric symptoms. RESULTS: Mismatch negativity amplitude was reduced in the patients with schizophrenia. They showed a greater left-less-than-right asymmetry than comparison subjects at homotopic electrode pairs near the parietotemporal junction. There were correlations between mismatch negativity amplitude and hallucinations at left frontal electrodes and between mismatch negativity amplitude and passive-apathetic social withdrawal at left and right frontal electrodes. CONCLUSIONS: Mismatch negativity was reduced in schizophrenia, especially in the left hemisphere. This finding is consistent with abnormalities of primary or adjacent auditory cortex involved in auditory sensory or echoic memory.

Increased rate of P300 latency prolongation with age in schizophrenia. Electrophysiological evidence for a neurodegenerative process.

BACKGROUND: The latency of the P300 event-related potential is prolonged in disorders associated with neural damage and degeneration and also becomes prolonged in the course of neural changes that accompany aging. We tested whether the rate of P300 latency increase with age was greater in male schizophrenic patients than in normal subjects because a steeper slope in schizophrenia would suggest a progressive neurodegenerative process. We also evaluated a subset of these subjects for changes in brain volumes as determined by magnetic resonance imaging. METHOD: The P300 component was elicited during an auditory "oddball" paradigm and was recorded from 47 male patients with chronic schizophrenia whose mean age at onset was 22.4 years and from 47 age-, handedness-, and gender-matched control subjects. The relation of P300 latency and amplitude to age within each group was evaluated using correlation and regression analyses. Brain volumes determined via magnetic resonance imaging were evaluated by quantitative volumetric analyses of images acquired with three-dimensional Fourier transform and double echo-spin echo-pulse sequences. RESULTS: The slope of P300 latency on age was steeper for schizophrenic patients than for normal control subjects at midline frontal and central electrode sites. The slope of N100 latency did not differ, implying that the P300 differences were not likely to be due to peripheral hearing loss or damage affecting the initial stages of neural processing. Posterior superior temporal gyrus gray matter volume determined via magnetic resonance imaging significantly diminished with age on the left side in patients with schizophrenia but not on the right side or in controls; these slopes were not, however, statistically significantly different from each other. CONCLUSIONS: These findings provide preliminary evidence that male patients with chronic schizophrenia experience a neurodegenerative process that becomes evident in adulthood and is reflected by the rate of change of P300 latency with age. Whether this process is due to the primary effects of schizophrenia or is secondary to factors associated with schizophrenia's chronic course and treatment remains a question for future investigation.

Auditory ERPs to non-target stimuli in schizophrenia: relationship to probability, task-demands, and target ERPs.

The effects of task demands and stimulus probability on the N1 and P2 components of the auditory event-related potential (ERP) to non-target stimuli were investigated in normal and medicated schizophrenic subjects. Subjects either read a book while tones were presented, or counted the rare (low probability) tones in an auditory oddball paradigm. The mismatch negativity to rare tones in the reading condition was present, and did not differ between groups. N1 amplitude was smaller in schizophrenic patients in all conditions. When subjects counted the rare tones, the amplitude and latency of P2 increased. This task-related effect on P2 was much greater in control than in schizophrenic subjects. Difference ERPs were used to better characterize the effect of task demands by subtracting the ERP in the reading condition from the ERP in the counting condition. The difference ERP consisted of a negative deflection at 182 ms, and a positive deflection at 276 ms, which were both reduced in schizophrenic subjects. N2 and P3 amplitude to target stimuli were reduced in patients as well, but these abnormalities were uncorrelated with N1 and P2 abnormalities to non-target stimuli. Despite automatic registration of stimulus mismatch, and normal processing speed, patients showed deficient task-related modulation of processing to both non-target and target stimuli. Reduction of N1 amplitude in schizophrenia occurs regardless of task demands, and may reflect a chronic, early-stage disturbance in information processing.

Parametric manipulations of auditory stimuli differentially affect P3 amplitude in schizophrenics and controls.

Schizophrenics show P3 amplitude reduction and topographic asymmetries. It is unclear whether the underlying cause of these deficits is primarily functional or structural. This study examined the effect of stimulus discriminability and task instruction on behavioral performance and P3 in schizophrenics and normal control subjects. Stimulus discriminability was manipulated by varying the overall loudness and pitch disparity of the two tones in an auditory oddball paradigm. Instructions emphasized either speed or accuracy of response. Instructions had no significant effects on reaction time, perceptual sensitivity, response bias, or P3. With increased discriminability, however, both groups improved in mean reaction time to targets and perceptual sensitivity. In controls, P3 became earlier and larger with increased stimulus discriminability and was consistently larger over left temporal areas than over right temporal areas. In schizophrenics, P3 latency was related to stimulus discriminability, but amplitude was not; P3 amplitude did not increase with improvement of perceptual sensitivity and reaction time. Unlike normal controls, schizophrenics had a P3 asymmetry at temporal sites, with reduced left-sided voltages. The results are not consistent with a primarily functional cause of P3 aberrations in schizophrenia and are compatible with the hypothesis that P3 amplitude deficits in schizophrenia are related to underlying pathophysiology of temporal lobe generator sites.

Electrical source analysis of auditory ERPs in medial temporal lobe amnestic syndrome.

Auditory event-related potential (ERP) components have been anatomically linked to temporal lobe structures and functionally related to attentional and memory processes. We recorded auditory ERPs using an "oddball" paradigm from two patients with amnestic syndromes secondary to medial temporal lobe encephalitic infections. The oddball paradigm elicits the exogenous N1 and P2 components, and the endogenous N2 and P3 components. Electrical source analysis was used to test for alterations in source strength and orientation in these patients compared to control subjects. Symmetric dipoles placed in the temporal lobe region were used to measure ERP component activity. In the patient with a lesion confined to the left, medial temporal lobe, including the posterior hippocampus, dipole orientation was displaced anteriorally. In the patient with lesions to the anterior medial temporal lobe, temporal poles, and orbital frontal cortex, the negative components of the ERP (N1 and N2) were reduced in the right hemisphere, accompanied by disturbed orientation. These findings are consistent with other evidence that the different components of the auditory ERP can be dissociated on the basis of lesion effects, and that the antero-posterior extent of encephalitic lesions may play an important role in modulating ERP abnormalities.