Distinct population and single-neuron selectivity for executive and episodic processing in human dorsal posterior cingulate
Curation statements for this article:-
Curated by eLife
Evaluation Summary:
This manuscript provides new insights into one of the most enigmatic brain regions; the posterior cingulate cortex. Using electrophysiological recordings from dorsal and ventral PCC subregions, the authors provide evidence for a dorsal-executive and ventral-episodic functional subdivision. This paper will be of high interest to a broad range of neuroscientists.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (eLife)
- Neuroscience (eLife)
Abstract
Posterior cingulate cortex (PCC) is an enigmatic region implicated in psychiatric and neurological disease, yet its role in cognition remains unclear. Human studies link PCC to episodic memory and default mode network (DMN), while findings from the non-human primate emphasize executive processes more associated with the cognitive control network (CCN) in humans. We hypothesized this difference reflects an important functional division between dorsal (executive) and ventral (episodic) PCC. To test this, we utilized human intracranial recordings of population and single unit activity targeting dorsal PCC during an alternated executive/episodic processing task. Dorsal PCC population responses were significantly enhanced for executive, compared to episodic, task conditions, consistent with the CCN. Single unit recordings, however, revealed four distinct functional types with unique executive (CCN) or episodic (DMN) response profiles. Our findings provide critical electrophysiological data from human PCC, bridging incongruent views within and across species, furthering our understanding of PCC function.
Article activity feed
-
-
Evaluation Summary:
This manuscript provides new insights into one of the most enigmatic brain regions; the posterior cingulate cortex. Using electrophysiological recordings from dorsal and ventral PCC subregions, the authors provide evidence for a dorsal-executive and ventral-episodic functional subdivision. This paper will be of high interest to a broad range of neuroscientists.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)
-
Reviewer #1 (Public Review):
This is an exciting study using human electrophysiology to provide novel insights into the functional architecture of the posterior cingulate cortex (PCC). As the authors note, the PCC is an enigmatic brain region that is implicated across numerous cognitive functions and appears to play a crucial role in many neurological and neuropsychiatric conditions. Articulating the potential functional specialisations of subdivisions of the PCC to distinct aspects of cognition thus provides an innovative and powerful means of reconciling discrepancies in the extant literature, as well as stimulating new directions in the field.
Strengths of the study include the use of intracranial electrophysiology via local field potential and single-neuron recordings targeting the dorsal PCC. This approach enabled the authors to …
Reviewer #1 (Public Review):
This is an exciting study using human electrophysiology to provide novel insights into the functional architecture of the posterior cingulate cortex (PCC). As the authors note, the PCC is an enigmatic brain region that is implicated across numerous cognitive functions and appears to play a crucial role in many neurological and neuropsychiatric conditions. Articulating the potential functional specialisations of subdivisions of the PCC to distinct aspects of cognition thus provides an innovative and powerful means of reconciling discrepancies in the extant literature, as well as stimulating new directions in the field.
Strengths of the study include the use of intracranial electrophysiology via local field potential and single-neuron recordings targeting the dorsal PCC. This approach enabled the authors to capture neural activity in the dorsal PCC during alternating episodic and executive cognitive tasks and to localise the functional clustering of single unit activity to uncover functional cell types within PCC.
The experimental tasks seem well-designed, drawing on the current understanding of the role of the DMN in memory-based constructive simulation processes (past and future), and the executive attention tasks to index the CCN. I was also pleased to see the inclusion of a "rest" condition in which endogenously driven forms of spontaneous cognition would be predicted to occur. Overall, the manuscript is very well-written, and the major conclusions appear well supported by the data.
-
Reviewer #2 (Public Review):
The posterior cingulate is poorly understood in terms of its relationship to cognition, yet appears to be central to many brain networks. Much previous work has been based on functional MRI which is a highly indirect and slow measurement that shows a confusing set of relationships with other brain networks and different cognitive tasks. This study uses direct intracranial recordings to look at local field potentials and single unit activity patterns as participants performed different cognitive tasks. The results show that the dorsal posterior cingulate (at least across the high gamma range) looks like it is primarily involved in cognitive control tasks, rather than being task-negative or internally focused, as the fMRI literature suggests. Perhaps most interesting is the cluster analysis of the single unit …
Reviewer #2 (Public Review):
The posterior cingulate is poorly understood in terms of its relationship to cognition, yet appears to be central to many brain networks. Much previous work has been based on functional MRI which is a highly indirect and slow measurement that shows a confusing set of relationships with other brain networks and different cognitive tasks. This study uses direct intracranial recordings to look at local field potentials and single unit activity patterns as participants performed different cognitive tasks. The results show that the dorsal posterior cingulate (at least across the high gamma range) looks like it is primarily involved in cognitive control tasks, rather than being task-negative or internally focused, as the fMRI literature suggests. Perhaps most interesting is the cluster analysis of the single unit activity patterns, which highlights the clear functional heterogeneity of different units within the dorsal posterior cingulate. These findings show the complexity at play within this region and have many implications for future work both in intracranial recording, and neuroimaging, but also in clinical and pharmacological studies that repeatedly find and interpret differences in this region.
-
Reviewer #3 (Public Review):
The present study aims to elucidate posterior cingulate cortex (PCC) function with both single-unit and population-level depth electrodes. The results clearly show that the dorsal PCC (dPCC) is involved in executive functions (search and add), but that it also contains neurons that are selective for episodic memory (past and future) and rest conditions. With this impressive study design, the authors are able to reconcile discrepancies between human and primate studies. Furthermore, the derived conclusion that PCC function is more diverse than merely its participation in the DMN is of great importance for the field. Thus, I believe that this work will have a great impact on how we think about the PCC, by (1) emphasizing its participation in executive processes and (2) providing evidence of distinct …
Reviewer #3 (Public Review):
The present study aims to elucidate posterior cingulate cortex (PCC) function with both single-unit and population-level depth electrodes. The results clearly show that the dorsal PCC (dPCC) is involved in executive functions (search and add), but that it also contains neurons that are selective for episodic memory (past and future) and rest conditions. With this impressive study design, the authors are able to reconcile discrepancies between human and primate studies. Furthermore, the derived conclusion that PCC function is more diverse than merely its participation in the DMN is of great importance for the field. Thus, I believe that this work will have a great impact on how we think about the PCC, by (1) emphasizing its participation in executive processes and (2) providing evidence of distinct single-unit response profiles that do not manifest on a population level.
The main strength of this work is the combination of population-level measurements that clearly show the participation of dPCC in executive processes with microelectrode single-unit measurements and an unsupervised hierarchical clustering approach that allows for the identification of 4 distinct SU response profiles within the dPCC. In addition, the population-level electrodes mostly engaged in executive function cluster around an fMRI meta-analysis peak related to executive processing derived from neurosynth, providing a bridge to human fMRI research.
Nevertheless, there is one concern regarding the data collected within the ventral PCC (vPCC) in this study and the way the authors integrated it into their conclusions.
Specifically, the conclusion that "Together, they [the findings] inform a view of PCC as a heterogeneous region composed of dorsal and ventral subregions specializing in executive and episodic processing respectively" may not be completely supported by the data. The dPCC macroelectrode data does clearly show a functional specialization in executive processing, but does the data from vPCC presented in this manuscript also support the claim? While taking a closer look at the vPCC data, several inconsistencies stood out: First, the total number of vPCC electrodes was much smaller (6 vs 29 microelectrodes and one microwire probe that was not analyzed). Second, it is not clear which of the presented electrodes in figure 3 were considered to be ventral. From comparing figure 3 with the dorsal/ventral split displayed in figure 1B, it seems as if only one electrode was unambiguously placed in vPCC. Third, BBG statistics of these 6 electrodes are not presented, thus the claim that they show vPCC functional specialization is not statistically supported.
-
