Case studies in neuroscience: reversible signatures of edema following electric and piezoelectric craniotomy drilling in macaques.

In vivo electrophysiology requires direct access to brain tissue, necessitating the development and refinement of surgical procedures and techniques that promote the health and well-being of animal subjects. Here, we report a series of findings noted on structural magnetic resonance imaging (MRI) scans in monkeys with MRI-compatible implants following small craniotomies that provide access for intracranial electrophysiology. We found distinct brain regions exhibiting hyperintensities in T2-weighted scans that were prominent underneath the sites at which craniotomies had been performed. We interpreted these hyperintensities as edema of the neural tissue and found that they were predominantly present following electric and piezoelectric drilling, but not when manual, hand-operated drills were used. Furthermore, the anomalies subsided within 2-3 wk following surgery. Our report highlights the utility of MRI-compatible implants that promote clinical examination of the animal's brain, sometimes revealing findings that may go unnoticed when incompatible implants are used. We show replicable differences in outcome when using electric versus mechanical devices, both ubiquitous in the field. If electric drills are used, our report cautions against electrophysiological recordings from tissue directly underneath the craniotomy for the first 2-3 wk following the procedure due to putative edema.NEW & NOTEWORTHY Close examination of structural MRI in eight nonhuman primates following craniotomy surgeries for intracranial electrophysiology highlights a prevalence of hyperintensities on T2-weighted scans following surgeries conducted using electric and piezoelectric drills, but not when using mechanical, hand-operated drills. We interpret these anomalies as edema of neural tissue that resolved 2-3 wk postsurgery. This finding is especially of interest as electrophysiological recordings from compromised tissue may directly influence the integrity of collected data immediately following surgery.

Time context of cue-outcome associations represented by neurons in perirhinal cortex.

The perirhinal cortex (PRh), which has extensive connections with diverse brain sites, may contribute to semantic memory by associating various types of information about objects. However, the extent of the types of associations in which PRh participates is unknown. In the present study, we let monkeys experience a consistent contingency between visual cues and different types of outcomes (water reward and sound-only acknowledgment) in a particular time context for many days and then recorded neuronal activities from PRh and area TE, which is the major source of visual inputs to PRh. We found that PRh cells represented the outcome type in their responses to the visual cues only in the time context in which the monkeys had experienced the cue-outcome contingency. In contrast, TE cells represented the outcome information whenever the cue appeared (i.e., independently from the related time context). These results showed that PRh cells represented not only the cue-outcome contingency but also the time context in which the monkeys had experienced the contingency. We conclude that PRh is not specific to the representation of sensory and associative properties of objects themselves but may represent broader information about objects, including the time context in which the objects are associated with particular outcomes.

A causal role for the pulvinar in coordinating task-independent cortico-cortical interactions.

The pulvinar is the largest nucleus in the primate thalamus and has topographically organized connections with multiple cortical areas, thereby forming extensive cortico-pulvino-cortical input-output loops. Neurophysiological studies have suggested a role for these transthalamic pathways in regulating information transmission between cortical areas. However, evidence for a causal role of the pulvinar in regulating cortico-cortical interactions is sparse and it is not known whether pulvinar's influences on cortical networks are task-dependent or, alternatively, reflect more basic large-scale network properties that maintain functional connectivity across networks regardless of active task demands. In the current study, under passive viewing conditions, we conducted simultaneous electrophysiological recordings from ventral (area V4) and dorsal (lateral intraparietal area [LIP]) nodes of macaque visual system, while reversibly inactivating the dorsal part of the lateral pulvinar (dPL), which shares common anatomical connectivity with V4 and LIP, to probe a causal role of the pulvinar. Our results show a significant reduction in local field potential phase coherence between LIP and V4 in low frequencies (4-15 Hz) following muscimol injection into dPL. At the local level, no significant changes in firing rates or LFP power were observed in LIP or in V4 following dPL inactivation. Synchronization between pulvinar spikes and cortical LFP phase decreased in low frequencies (4-15 Hz) both in LIP and V4, while the low frequency synchronization between LIP spikes and pulvinar phase increased. These results indicate a causal role for pulvinar in synchronizing neural activity between interconnected cortical nodes of a large-scale network, even in the absence of an active task state.

Dynamic pulvino-cortical interactions in the primate attention network.

While research in previous decades demonstrated a link between the pulvinar nucleus of the thalamus and visual selective attention, the pulvinar's specific functional role has remained elusive. However, methodological advances in electrophysiological recordings in non-human primates, including simultaneous recordings in multiple brain regions, have recently begun to reveal the pulvinar's functional contributions to selective attention. These new findings suggest that the pulvinar is critical for the efficient transmission of sensory information within and between cortical regions, both synchronizing cortical activity across brain regions and controlling cortical excitability. These new findings further suggest that the pulvinar's influence on cortical processing is embedded in a dynamic selection process that balances sensory and motor functions within the large-scale network that directs selective attention.

Anatomical inputs to sulcal portions of areas 9m and 8Bm in the macaque monkey.

Neuronal activities recorded from the dorsal bank of the anterior cingulate sulcus have suggested that this cortical area is involved in control of search vs. repetition, goal-based action selection and encoding of prediction error regarding action value. In this study, to explore potential anatomical bases for these neuronal activities, we injected retrograde tracers (CTB-Alexa-488 and CTB-gold) into the dorsal bank of the anterior cingulate sulcus and examined the distribution of labeled cell bodies in macaque monkey brains. The Nissl staining showed that the cortex in the dorsal bank of the anterior cingulate sulcus has consistent layer 4 which means that the cortical region is a part of the granular prefrontal cortex. The injection site belonged to the sulcal portion of area 9m in two cases and the sulcal portion of area 8Bm in one case. In addition to the continuous distribution of labeled cells in the two areas (areas 9m and 8Bm) around the injection site, the labeled cells were densely distributed in the cingulate areas (areas 24, 32, and 23) in all the cases. The dense labeling of cells was also found in other prefrontal areas (areas 46, 10, 11, and 12) in the two cases with injection into the sulcal portion of area 9m, whereas the dense labeling of cells was found in pre-motor areas (F6 and F7) in the case with injection into the sulcal portion of area 8Bm. The dense labeling of cells in the prefrontal and premotor areas was more similar to those previously found after injections into dorsal parts of areas 9 and 8B. Subcortical distribution of labeled cells was found in the mediodorsal nucleus of thalamus, claustrum, and substantia nigra pars compacta in all the cases.