Rhythmic interactions between the mediodorsal thalamus and prefrontal cortex precede human visual perception.

The thalamus is much more than a simple sensory relay. High-order thalamic nuclei, such as the mediodorsal thalamus, exert a profound influence over animal cognition. However, given the difficulty of directly recording from the thalamus in humans, next-to-nothing is known about thalamic and thalamocortical contributions to human cognition. To address this, we analysed simultaneously-recorded thalamic iEEG and whole-head MEG in six patients (plus MEG recordings from twelve healthy controls) as they completed a visual detection task. We observed that the phase of both ongoing mediodorsal thalamic and prefrontal low-frequency activity was predictive of perceptual performance. Critically however, mediodorsal thalamic activity mediated prefrontal contributions to perceptual performance. These results suggest that it is thalamocortical interactions, rather than cortical activity alone, that is predictive of upcoming perceptual performance and, more generally, highlights the importance of accounting for the thalamus when theorising about cortical contributions to human cognition.

Thalamic interictal epileptiform discharges in deep brain stimulated epilepsy patients.

The relationships between interictal epileptiform discharges (IEDs) in the anterior (ANT) and dorsomedial nuclei (DMNT) of the thalamus and electro-clinical parameters in pharmacoresistant focal epilepsy patients receiving intrathalamic electrodes for deep brain stimulation (DBS) were investigated. Thalamus-localized IEDs (LIEDs) and surface EEG (sEEG)-IEDs were evaluated in eight patients who underwent ANT-DBS. Occurrence and frequency of ANT- and DMNT-LIEDs and pre-operative sEEG-IEDs were examined with respect to seizure onset location and seizure outcome following ANT-DBS. LIEDs were identified in all eight patients, in the ANT, DMNT, or both. ANT-LIEDs were observed in all patients with an unequivocal temporal seizure onset zone. The ANT-LIED frequency correlated with pre-surgical sEEG-IED frequency (ρ = 0.76, p = 0.033) and predicted ANT-DBS responsiveness (T = -2.6; p = 0.0428). Of the five patients with bilateral sEEG-IEDs, all had ANT-LIEDs, but only one patient had DMNT-LIEDs. All patients with no or unilateral sEEG-IEDs had DMNT-LIEDs. Observation of LIEDS in the ANT and DMNT supports the hypothesis that these nuclei are involved in propagation of focal epileptic activity. Their correspondence with differing electro-clinical features suggests that these nuclei are functionally distinguishable nodes within the epileptic networks of individual patients.

Thalamic theta phase alignment predicts human memory formation and anterior thalamic cross-frequency coupling.

Previously we reported electrophysiological evidence for a role for the anterior thalamic nucleus (ATN) in human memory formation (Sweeney-Reed et al., 2014). Theta-gamma cross-frequency coupling (CFC) predicted successful memory formation, with the involvement of gamma oscillations suggesting memory-relevant local processing in the ATN. The importance of the theta frequency range in memory processing is well-established, and phase alignment of oscillations is considered to be necessary for synaptic plasticity. We hypothesized that theta phase alignment in the ATN would be necessary for memory encoding. Further analysis of the electrophysiological data reveal that phase alignment in the theta rhythm was greater during successful compared with unsuccessful encoding, and that this alignment was correlated with the CFC. These findings support an active processing role for the ATN during memory formation.

Corticothalamic phase synchrony and cross-frequency coupling predict human memory formation.

The anterior thalamic nucleus (ATN) is thought to play an important role in a brain network involving the hippocampus and neocortex, which enables human memories to be formed. However, its small size and location deep within the brain have impeded direct investigation in humans with non-invasive techniques. Here we provide direct evidence for a functional role for the ATN in memory formation from rare simultaneous human intrathalamic and scalp electroencephalogram (EEG) recordings from eight volunteering patients receiving intrathalamic electrodes implanted for the treatment of epilepsy, demonstrating real-time communication between neocortex and ATN during successful memory encoding. Neocortical-ATN theta oscillatory phase synchrony of local field potentials and neocortical-theta-to-ATN-gamma cross-frequency coupling during presentation of complex photographic scenes predicted later memory for the scenes, demonstrating a key role for the ATN in human memory encoding.

Memory signals from the thalamus: early thalamocortical phase synchronization entrains gamma oscillations during long-term memory retrieval.

The thalamus is believed to be a key node in human memory networks, however, very little is known about its real-time functional role. Here we examined the dynamics of thalamocortical communication during long-term episodic memory retrieval in two experiments. In experiment 1, intrathalamic and surface EEG was recorded in an epileptic patient implanted with depth electrodes for brain stimulation therapy. In a recognition memory test, early (300-500 ms) stimulus-linked oscillatory synchrony between mediodorsal thalamic and frontal surface electrodes at beta frequency (20 Hz) was enhanced for correctly remembered old compared to correctly rejected new items. Directionality measures (Granger causality) indicated that the thalamus was the sender, and the neocortex the receiver, of this beta signal, which also modulated the power of neocortical gamma (55-80 Hz) oscillations (cross-frequency coupling). Experiment 2 validated the cross-frequency coupling effects in a healthy participant sample. Confirming the findings from experiment 1, significantly increased cross-frequency coupling was found over frontal scalp electrodes during successful recognition. Extending anatomical knowledge on thalamic connectivity with frontal neocortex, these results suggest that the thalamus sends an early memory signal to frontal regions, triggering further memory search processes.