Abstracts

Rationale: During wakefulness, inhibition by the thalamic reticular neurons (TRN), which encase the other thalamic nuclei, gate the relay of sensory and motor information to cortex. Through this “sensory gating” the TRN attenuates the transmission of redundant and irrelevant stimuli to the cortex, protecting higher cognitive function from interference. In animal models, TRN neurons show a strong response to an initial auditory stimulus and an attenuated response to a repeated stimulus. The selective firing of TRN neurons correlates with better selective attention and sensory detection. Failure of TRN mediated inhibition results in the loss of the normal gating response, and loss of TRN neurons impairs behavior that depends on sensory selection. Deficient sensory gating measured using sensor space EEG recordings has been studied extensively and correlates with cognitive dysfunction and symptoms of inattention in attention deficit hyperactivity disorder. Conversely, stronger sensory gating correlates with improved impulse control in gifted children.

Methods: We evaluated thalamic and cortical auditory evoked responses and sensory gating using a paired auditory stimulation paradigm in subjects undergoing direct thalamic recording during epilepsy surgery evaluation. Subjects passively listened to ~240 paired auditory stimuli, including an initial auditory click, stimulus 1 (S1) followed by second click, stimulus 2 (S2) with an interstimulus interval of 500 msec, separated by intertrial intervals of 8-10 sec. Simultaneous intracranial EEG recordings from the thalamus and scalp EEG recordings from FZ and CZ electrodes were analyzed. Data were bandpass filtered (6.0-30.0 Hz) then epoched into single trials. Trials were rejected if the peak-to-peak amplitude exceeded a manually determined threshold for each channel. Evoked responses were visually confirmed if consistent across at least 2 references (C2 spinous process, average reference and/or white matter reference). When present, the amplitude of the P50 responses (relative to the preceding negative trough) were recorded following S1 and S2 to calculate an S2 to S1 P50 amplitude ratio.

Results: We identified a P50 thalamic response in two of four subjects with direct centromedian thalamic recordings (Fig1). The S2/S1 ratio was 0.82 (range 0.79-0.85) in the thalamus, 0.36 (range 0.35-0.36) at CZ and 0.42 (range 0.41-0.42) at Fz.

Conclusions: These results identify that a P50 auditory evoked response is evident in the centromedian nucleus of the thalamus. In these pilot data, auditory sensory gating was present in the scalp and to a lesser degree in the thalamus. Future work will evaluate the auditory gating response in other thalamic nuclei and in response to other sensory stimuli to determine domain specificity and relate these findings to measures of inattention.

Funding: Please list any funding that was received in support of this abstract.: CJC and MAK are supported by NIH NINDS R01NS11586.