Markku Penttonen

Auditory cortical event-related potentials to pitch deviances in rats

We recorded epidural event-related potentials (ERPs) from the auditory cortex in anesthetized rats when pitch-deviant tones were presented in a homogeneous 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. Furthermore, as the difference between ERPs to deviant tones and those to standard tones at the 63-196 ms latency range could be detected only when standard tones precede deviant tones it shows concordance with mismatch negativity in humans.

Mismatch Negativity (MMN) in Freely-Moving Rats with Several Experimental Controls

Mismatch negativity (MMN) is a scalp-recorded electrical potential that occurs in humans in response to an auditory stimulus that defies previously established patterns of regularity. MMN amplitude is reduced in people with schizophrenia. In this study, we aimed to develop a robust and replicable rat model of MMN, as a platform for a more thorough understanding of the neurobiology underlying MMN. One of the major concerns for animal models of MMN is whether the rodent brain is capable of producing a human-like MMN, which is not a consequence of neural adaptation to repetitive stimuli. We therefore tested several methods that have been used to control for adaptation and differential exogenous responses to stimuli within the oddball paradigm. Epidural electroencephalographic electrodes were surgically implanted over different cortical locations in adult rats. Encephalographic data were recorded using wireless telemetry while the freely-moving rats were presented with auditory oddball stimuli to assess mismatch responses. Three control sequences were utilized: the flip-flop control was used to control for differential responses to the physical characteristics of standards and deviants; the many standards control was used to control for differential adaptation, as was the cascade control. Both adaptation and adaptation-independent deviance detection were observed for high frequency (pitch), but not low frequency deviants. In addition, the many standards control method was found to be the optimal method for observing both adaptation effects and adaptation-independent mismatch responses in rats. Inconclusive results arose from the cascade control design as it is not yet clear whether rats can encode the complex pattern present in the control sequence. These data contribute to a growing body of evidence supporting the hypothesis that rat brain is indeed capable of exhibiting human-like MMN, and that the rat model is a viable platform for the further investigation of the MMN and its associated neurobiology.

Memory-based mismatch response to frequency changes in rats.

Any occasional changes in the acoustic environment are of potential importance for survival. In humans, the preattentive detection of such changes generates the mismatch negativity (MMN) component of event-related brain potentials. MMN is elicited to rare changes (‘deviants’) in a series of otherwise regularly repeating stimuli (‘standards’). Deviant stimuli are detected on the basis of a neural comparison process between the input from the current stimulus and the sensory memory trace of the standard stimuli. It is, however, unclear to what extent animals show a similar comparison process in response to auditory changes. To resolve this issue, epidural potentials were recorded above the primary auditory cortex of urethane-anesthetized rats. In an oddball condition, tone frequency was used to differentiate deviants interspersed randomly among a standard tone. Mismatch responses were observed at 60–100 ms after stimulus onset for frequency increases of 5% and 12.5% but not for similarly descending deviants. The response diminished when the silent inter-stimulus interval was increased from 375 ms to 600 ms for +5% deviants and from 600 ms to 1000 ms for +12.5% deviants. In comparison to the oddball condition the response also diminished in a control condition in which no repetitive standards were presented (equiprobable condition). These findings suggest that the rat mismatch response is similar to the human MMN and indicate that anesthetized rats provide a valuable model for studies of central auditory processing.

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

In 1978, Berry and Thompson showed that the amount of theta (3-8Hz) 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 and also that in these animals the theta ratio was higher throughout both experimental phases. In fact, while the hippocampal theta ratio remained stable in the fast learners as a function of training, it decreased in the slow learners already during unpaired training. In addition, the presence of hippocampal theta activity enhanced the hippocampal model of the conditioned response (CR) and seemed to be beneficial for CR performance in terms of peak latency during conditioning, but did not have any effect when the animals showed asymptotic learning. Together with earlier findings, these results imply that the behavioral state in which hippocampal theta activity is absent is detrimental for learning, and that the behavioral state in which hippocampal theta activity dominates is beneficial for learning, at least before a well-learned state is achieved.

Auditory Cortical and Hippocampal-System Mismatch Responses to Duration Deviants in Urethane-Anesthetized Rats

Any change in the invariant aspects of the auditory environment is of potential importance. The human brain preattentively or automatically detects such changes. The mismatch negativity (MMN) of event-related potentials (ERPs) reflects this initial stage of auditory change detection. The origin of MMN is held to be cortical. The hippocampus is associated with a later generated P3a of ERPs reflecting involuntarily attention switches towards auditory changes that are high in magnitude. The evidence for this cortico-hippocampal dichotomy is scarce, however. To shed further light on this issue, auditory cortical and hippocampal-system (CA1, dentate gyrus, subiculum) local-field potentials were recorded in urethane-anesthetized rats. A rare tone in duration (deviant) was interspersed with a repeated tone (standard). Two standard-to-standard (SSI) and standard-to-deviant (SDI) intervals (200 ms vs. 500 ms) were applied in different combinations to vary the observability of responses resembling MMN (mismatch responses). Mismatch responses were observed at 51.5–89 ms with the 500-ms SSI coupled with the 200-ms SDI but not with the three remaining combinations. Most importantly, the responses appeared in both the auditory-cortical and hippocampal locations. The findings suggest that the hippocampus may play a role in (cortical) manifestation of MMN.

Disrupting neural activity related to awake-state sharp wave-ripple complexes prevents hippocampal learning

Oscillations in hippocampal local-field potentials (LFPs) reflect the crucial involvement of the hippocampus in memory trace formation: theta (4–8 Hz) oscillations and ripples (~200 Hz) occurring during sharp waves are thought to mediate encoding and consolidation, respectively. During sharp wave-ripple complexes (SPW-Rs), hippocampal cell firing closely follows the pattern that took place during the initial experience, most likely reflecting replay of that event. Disrupting hippocampal ripples using electrical stimulation either during training in awake animals or during sleep after training retards spatial learning. Here, adult rabbits were trained in trace eyeblink conditioning, a hippocampus-dependent associative learning task. A bright light was presented to the animals during the inter-trial interval (ITI), when awake, either during SPW-Rs or irrespective of their neural state. Learning was particularly poor when the light was presented following SPW-Rs. While the light did not disrupt the ripple itself, it elicited a theta-band oscillation, a state that does not usually coincide with SPW-Rs. Thus, it seems that consolidation depends on neuronal activity within and beyond the hippocampus taking place immediately after, but by no means limited to, hippocampal SPW-Rs.

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 interpretation was shown to be apparent. A need for additional control procedures revealing a contribution of neural orienting responses in animal MMN experiments is discussed.

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.

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 characteristics of the conditioned orienting head movements. The results are discussed in the context of a cat analogue of the human mismatch negativity (MMN) and a role of the hippocampal formation to model and predict the conditioned behavioral orienting responses.

Sympathetic nervous system synchrony in couple therapy

The aim of this study was to test whether there is statistically significant sympathetic nervous system (SNS) synchrony between participants in couple therapy. To our knowledge, this is the first study to measure psychophysiological synchrony during therapy in a multiactor setting. The study focuses on electrodermal activity (EDA) in the second couple therapy session from 10 different cases (20 clients, 10 therapists working in pairs). The EDA concordance index was used as a measure of SNS synchrony between dyads, and synchrony was found in 85% of all the dyads. Surprisingly, co-therapists exhibited the highest levels of synchrony, whereas couples exhibited the lowest synchrony. The client-therapist synchrony was lower than that of the co-therapists, but higher than that of the couples. A Video Abstract is available next to the online version of this article on the JMFT web site.