Low-noise microvolt level calibrator for measurement of performance of biosignal recording systems

A calibrator, the noise level of which is below the noise level generated in the preamplifier system, was needed for testing and development of a multichannel recording system. A multichannel preamplifier head assembly was used for recording cortical, subcortical, and cerebellar slow potentials and multiunit activity in freely moving cats and restrained rabbits. An inexpensive, battery-powered, lownoise voltage signal generator for calibration of the preamplifiers is described. The circuit provides a square-wave output at a frequency of 10 or 1000 Hz, and the peak-to-peak (p-p) amplitude can be selected at 10, 100, or 1000µV. The measured output noise of the calibrator is below 2µV (p-p, 0.…

Activity in the rabbit somatosensory cortex reflects the active procedural memory trace of a classically conditioned eyeblink response.

Behavioral responses and neural responses in the somatosensory cortex were recorded in nine rabbits during the unpaired and paired treatments of classical eyeblink conditioning with a tone conditioned stimulus (CS) and an airpuff unconditioned stimulus. During the unpaired treatment, neither the behavioral nor neural responses to the CS were observed. During the paired treatment, behavioral conditioned response (CR), accompanied by neural activity, was developed. In well-trained animals occasional failures to elicit the CR were accompanied by an absence of neural responses. Nevertheless, the CS modified the behavioral unconditioned response in paired trials, implying that the CR-failures co…

Bilaterally recorded multiple-unit activity of the cingulate cortex during head turning conditioning with unilateral medial forebrain bundle stimulation.

Cats were conditioned to turn their heads using a tone conditioned stimulus (CS) and medial forebrain bundle stimulation (MFB) unconditioned stimulus (US). The CS+ was delivered to one ear at a time, in random order, followed by the US. A tone of a different frequency was used as a CS-. The cats learned to respond differentially to the CSs showing head movements of greater acceleration to the CS+ than CS- over sessions. Bilateral recordings of cingulate cortex multiple-unit activity showed increased response amplitudes over sessions and larger responses in the hemisphere ipsilateral to the US. Since ipsilateral multiple-unit responses did not differ for the CSs, the asymmetry was probably d…

A method for rapid implantation of multielectrode systems.

The implantation of several chronic electrodes at the same time was needed for the studies in which both evoked slow potential and multiple unit neural activity of different brain sites were recorded during classical conditioning in freely moving cats. The recording electrodes were made of 25-75 microns insulated stainless steel or nichrome wires which were inserted into a thin hypodermic needle of a fixed, calibrated length. The fast implantation system described here is based on the use of a stereotaxic frame as a stand for a drill and as a support for an electrode holder with which the electrodes were implanted through precision holes drilled directly according to the coordinates of the …

Hippocampal theta-band activity and trace eyeblink conditioning in rabbits.

The authors examined the relationship between hippocampal theta activity and trace eyeblink conditioning. Hippocampal electrophysiological local field potentials were recorded before, during, and after conditioning or explicitly unpaired training sessions in adult male New Zealand White rabbits. As expected, a high relative power of theta activity (theta ratio) in the hippocampus predicted faster acquisition of the conditioned response during trace conditioning but, contrary to previous results obtained using the delay paradigm, only in the initial stage of learning. The presentation of the conditioned stimulus overall elicited an increase in the hippocampal theta ratio. The theta ratio dec…

Interpositus nucleus inactivation reduces unconditioned response amplitude after paired but not explicitly unpaired treatment in rabbit eyeblink conditioning.

The amplitude of unconditioned responses (URs) in unconditioned stimulus (US) alone presentations were measured in six rabbits during explicitly unpaired and classical conditioning treatments. After both phases of the experiment, the interpositus nucleus (IPN) was reversibly inactivated by a cold probe. URs after unpaired treatment were unaffected by inactivation but after acquisition of a robust level of conditioned responses (CRs), URs in US-alone test trials were reduced in amplitude compared with URs immediately before and after inactivation. The results suggest that the IPN has a role in CR-related reflex modification.

Three-dimensional Hall effect accelerometer for recording head movements of freely moving laboratory animals

A Hall effect device was constructed for a measurement of head movements in three spatial dimensions during classical conditioning experiments in cats. A Hall sensor was used to detect movements of a magnetic fragment floating in a small (15 x 15 mm) cube. The magnetic fragment was kept in the centre of the sealed cube with a thin coil spring which was filled with thin oil for damping excessive afteroscillations. A comparison of this device to a commercial accelerometer showed that the accuracy of the Hall device is sufficient for the movement recordings and that the device is sensitive also to slowly accelerating movements. The construction is compact and can be easily mounted, for example…

Hippocampal theta (3-8 Hz) activity during classical eyeblink conditioning in rabbits

In 1978, Berry and Thompson showed that the amount of theta (3–8 Hz) activity in the spontaneous hippocampal EEG predicted learning rate in subsequent eyeblink conditioning in rabbits. More recently, the absence of theta activity during the training trial has been shown to have a detrimental effect on learning rate. Here, we aimed to further explore the relationship between theta activity and classical eyeblink conditioning by determining how the relative power of hippocampal theta activity [theta/(theta + delta) ratio] changes during both unpaired control and paired training phases. We found that animals with a higher hippocampal theta ratio immediately before conditioning learned faster a…

Conditioned orienting (alpha) and delayed behavioral and evoked neural responses during classical conditioning

A differentiation of short-latency (alpha) and long-latency (delayed) classically conditioned behavioral and evoked neural (hippocampal) responses was attempted. Further, facilitation and retardation of these responses were studied in an experimental design in which 10 paired conditioning sessions either preceded (CC-CO group) or followed (CO-CC group) 10 randomly unpaired presentations of conditioned stimuli (CS) and unconditioned stimuli (UCS). A 2024-ms tone (1000 Hz) was delivered directly through a miniature earphone to the left ear, eliciting an orienting head movement ('alpha' response) to the left. The unconditioned stimulus (UCS) was a direct 1024-ms stimulation of the lateral hypo…

Inactivation of the interpositus nucleus blocks the conditioned response acquired by a somatosensory conditioned stimulus in rabbit eyeblink conditioning.

1. Earlier studies suggest that the memory trace for the conditioned eyeblink reflex is formed and maintained in the interpositus nucleus (IPN) in the deep cerebellar nuclei when either an auditory or visual stimulus is used as a conditioned stimulus (CS). 2. In the present study, the eyeblink reflex of the rabbit was conditioned to a somatosensory CS (an airpuff onto the back). 3. In well-trained animals, the IPN was reversibly inactivated by local cooling and the existence of the learned responses to the CS was then tested. 4. The reversible IPN inactivation blocked the memory trace the somatosensory CS. The finding further supports the view that IPN-mediated memory trace formation is not…

Behavioral and hippocampal evoked responses in an auditory oddball situation when an unconditioned stimulus is paired with deviant tones in the cat: Experiment II

Event-related potentials (ERP) in the areas CA1, CA3 and dentate fascia (Df) of the hippocampal formation were recorded during an oddball situation in the cat. A rewarding electrical stimulation of the lateral hypothalamus (US) was paired with deviant tones (2500 Hz) that occurred randomly in a series of the standard tones (2000 Hz) given to the left ear. In addition to developing orienting head movements to the side of the deviant tones, an increase in the amplitude of parallel hippocampal ERPs was observed. Both the behavioral and neural responses appeared not until a 50 ms latency range. Furthermore, time-amplitude characteristics of the ERPs corresponded to time-acceleration characteris…

Cooling of the cerebellar interpositus nucleus abolishes somatosensory cortical learning-related activity in eyeblink conditioned rabbits.

Nictitating membrane movement and multiple-unit activity in the somatosensory cortex were recorded from rabbits during paired (N = 6) and unpaired (N = 5) presentations of a tone conditioned stimulus (CS) and an airpuff unconditioned stimulus (US). A behavioural conditioned response (CR) to the CS and an accompanying neural response in the somatosensory cortex developed only in the paired group. Inactivation of the cerebellar interpositus nucleus abolished both the acquired CR and the accompanying neural response. However, the CS facilitated both behavioural and neural responses to the US during the inactivation. Thus, the absence of the CR could not be accounted for by the general inabilit…

ERPs to pitch changes: a result of reduced responses to standard tones in rabbits.

EVENT-RELATED potentials (ERPs) were recorded in rabbits when pitch deviant tones occurred in a series of standard tones (oddball situation). In control recordings, the deviant tones were presented without the standard tones (deviant-alone situation). In the oddball situation, significant difference ERPs (deviant ERPs - standard ERPs) could be found in the hippocampal and cerebellar recordings but not in the visual cortex. All the ERPs to the deviant stimuli observed in the oddball situation were also present in the deviant-alone situation. The difference ERPs were therefore based on reduced responses to the standards. The results are discussed in the context of a mismatch negativity (MMN) …

Hippocampal responses to pitch deviant tones in rabbits

A simple windows program for coding fast-changing events in observational situations divided into variable intervals

Hippocampal evoked potentials to pitch deviances in an auditory oddball situation in the rabbit: no human mismatch-like dependence on standard stimuli.

Hippocampal auditory evoked potentials (AEP) were recorded in 10 rabbits when pitch deviant tones occurred in a series of standard tones (oddball situation). In control recordings, deviant tones were presented without intervening standard tones (deviant-alone situation). All AEP deflections observed in the oddball situation were found also in the deviant-alone situation. Thus, it appeared that none of the AEP deflections to deviant tones in the oddball situation was specific to a memory trace of preceding standard tones. This observation was in contradiction to such a specificity of the mismatch negativity (MMN) found in humans. Instead, a connection to a neuronal orienting reaction interpr…

Auditory cortical event-related potentials to pitch deviances in rats

Abstract We recorded epidural event-related potentials (ERPs) from the auditory cortex in anesthetized rats when pitch-deviant tones were presented in a homogenous series of standard tones (oddball condition). Additionally, deviant tones were presented without standard tones (deviant-alone condition). ERPs to deviant tones in the oddball condition differed significantly from ERPs to standard tones at the latency range of 63–243 ms. On the other hand, ERPs to deviant tones in the deviant-alone condition did not differ from ERPs to standard tones until 196 ms from stimulus onset. The results suggest that oddball stimuli can be neurophysiologically discriminated in anesthetized rats. Furthermo…

Asymmetries in classically conditioned head movements and cingulate cortex slow potentials in cats.

Presuming that conditioned head movements in the cat indicate a preference for a specific direction, asymmetries were also expected to be found in bilaterally recorded cingulate cortex slow potentials to a symmetrical tone stimulus during discriminative conditioning. Conditioned stimuli (CS, 1000 and 2500 Hz tones) were delivered through two miniature loudspeakers fitted to the head in front of both ears. The unconditioned stimulus (US) was an electrical stimulation of either the left or right lateral hypothalamus yielding, in addition to its rewarding effects, an unconditioned head turning response (UR) either to the left, right, forwards or upwards. Discrimination learning appeared as mor…

Evidence of the origin of specific spontaneous head turns during intertrial intervals.

Direction and the frequency of spontaneous head movements during the ITIs following forward and backward paired trials were compared to an acquisition of a conditioned orienting (alpha) response directed to the side of the tone source. The head movements were analyzed from video recordings using classification of head turns to preferred and to nonpreferred directions. The results showed a significant increase in the alpha responses during the forward paired conditioning to the preferred direction and rapid extinction during the subsequent backward conditioning sessions. Spontaneous head movements during the ITIs increased to the same preferred direction as the conditioned alpha responses. T…

Hippocampal event-related potentials to pitch deviances in an auditory oddball situation in the cat: experiment I.

Hippocampal event-related potentials (ERP) in the areas CA1, CA3, and dentate fascia (Df) were recorded in cats during an oddball situation when pitch deviant tones occurred in a series of standard tones. When difference waves were calculated by subtracting ERPs to the standard tones from those to the deviant tones, no clear N40d, corresponding to a cat analogue of the human mismatch negativity (MMN) observed in earlier studies, could be detected. Instead, a prominent later negativity (N130d) was observed. A possible extra-hippocampal source of the process reflected by the MMN-like negativity, and a relation between an orienting response (OR) and the N130d are discussed.

The effect of rewarding hypothalamic stimulation on behavioral and neural hippocampal responses during trace eyeblink conditioning in rabbit (Oryctolagus cuniculus).

Rabbits were trace-conditioned with a tone as a conditioned stimulus and an airpuff as an unconditioned stimulus. Electrical stimulation to the medial forebrain bundle in the lateral hypothalamus was delivered either before or after the tone-airpuff pair. The purpose of the present study was to test whether the effect of post-trial hypothalamic stimulation differed from the effect of pre-trial hypothalamic stimulation on trace conditioning in the same subjects. Additionally, hippocampal responses were measured during sessions to see if hypothalamic stimulation activated dopaminergic fibres and affected hippocampal cell functioning and thus learning. The results showed that behavioral nictit…

Somatosensory event-related potentials in the rabbit cerebral and cerebellar cortices: a correspondence with mismatch responses in humans.

Somatosensory event-related potentials (ERPs) were recorded from the cerebellar (CerCx), somatosensory (SomCx) and visual (VCx) cortices in rabbits in two stimulus conditions. In the oddball condition, airpuffs to two different locations in the rabbit's muzzle corresponded to infrequently presented deviant stimuli (oddball-deviants) interspersed with frequently presented standard stimuli. In the deviant-alone condition, deviants (alone-deviants) were presented without standards. ERPs to oddball-deviants differed significantly from those to standards in CerCx and SomCx, but not in VCx. Furthermore, some of these differences were not found between ERPs to alone-deviants and those to standards…

Effects of rewarding electrical stimulation of lateral hypothalamus on classical conditioning of the nictitating membrane response.

1. Adult New Zealand albino rabbits were prepared with chronic hypothalamic stimulating electrodes and hippocampal recording electrodes. 2. Rabbits were restrained and classically conditioned by a tone CS and an airpuff US either followed or preceded by a hypothalamic stimulation (HS). Control rabbits were conditioned without the HS. 3. It was found that HS following the CS facilitated both behavioral and hippocampal responses, while HS preceding the CS inhibited them. 4. Enhanced hippocampal learning-related unit firing to the CS may represent an early indication of conditioning before the behavioral activity produces any observable change.

Unilateral medial forebrain bundle activation selectively enhances conditioned orienting head turns and ipsilateral cingulate cortex evoked field responses in cats

Effects of a unilateral medial forebrain bundle (MFB) stimulation unconditioned stimulus (US) on conditioned head turn and bilateral cingulate cortex field potentials were studied in cats. Conditioned stimuli (CSs) of different frequences were given randomly to either ear. The CS+ was followed by the US, and the CS— was presented alone. Before conditioning most cats predominantly turned toward the ear to which the CSs were presented, whereas after conditioning the head turns were in one direction, most prominently contralateral to the US. Negative field potentials were greater in the cingulate cortex ipsilateral to the US than in the cingulate cortex contralateral to the US. Cross correlati…

Multiple-unit responses to pitch changes in rabbits

Multiple-unit activity (MUA) was recorded from the hippocampus (Hc), the visual cortex (VCx) and the cerebellar cortex (CerCx) in rabbits when pitch deviant tones were presented in a series of standard tones (oddball situation) and when standard tones were absent (deviant-alone situation). Significant MMN-like responses (deviant responses minus standard responses in the oddball situation) occurred in Hc, reflecting a MUA increase to the standards and its decrease to the deviants. In accordance with parallel ERPs reported earlier, the MMN-like responses reflected responses only to different presentation frequencies of stimuli. Non-selectivity in the pitch of such responses in VCx and a lack …

The human brain processes visual changes that are not cued by attended auditory stimulation.

Event-related potentials (ERPs) to visual stimuli were recorded from the scalp of eight adult humans performing a task in which they counted vowels from a heard story. In the oddball condition, a repeated (standard) light bar of 50 ms in duration was rarely (P = 0.1) replaced by a (deviant) one differing in orientation from the standard. In the control condition, standards were simply omitted from the series and only (alone-) deviants retained. In both conditions, visual stimuli were asynchronous with auditory-task-relevant stimuli. ERPs to deviants significantly differed in amplitude from those to standards in the midline electrodes centrally, parietally and occipitally at 160-200 ms from …