A Precuneal Causal Loop Mediates External and Internal Information Integration in the Human Brain

TLDR: This study provides evidence that the medial posterior part of the DMN may drive interactions between large-scale networks, potentially allowing access to stored representations for moment to moment interpretation of an ever-changing environment.

Abstract: Human brains interpret external stimuli based on internal representations. One untested hypothesis is that the default-mode network (DMN) while responsible for internally oriented cognition can also encode externally oriented information. The unique neuroanatomical and functional fingerprint of the posterior part of the DMN supports a prominent role for the precuneus in this process. By utilising imaging data during two tasks from 100 participants, we found that the precuneus is functionally divided into dorsal and ventral subdivisions, each one differentially connecting to internally and externally oriented networks. The strength and direction of their connectivity is modulated by task difficulty in a manner dictated by the balance of internal versus external cognitive demands. Our study provides evidence that the medial posterior part of the DMN may drive interactions between large-scale networks, potentially allowing access to stored representations for moment to moment interpretation of an ever-changing environment.

Figures

Figure 5: PPI analyses for the two tasks revealed an inverse pattern of task modulated FC of the two seeds (v/dPCu’s), which is common to both tasks. (a) FC overviews for each task are shown in the circular connectogram plots. These were constructed by segmenting T-score PPI maps to anatomical regions as defined by the Harvard-Oxford cortical and subcortical structural atlases in the CONN toolbox (https://web.conn-toolbox.org/). Cerebellar regions are not

Figure 1: Meta-analysis and univariate analysis shows DMN engagement during the two tasks. (a) and (b) demonstrate the NeuroSynth meta-analysis results, using “attention*” or “execut*” as keywords to search for goal-directed tasks that require attention and executive function. (a) Forward inference shows that DMN subregions are active in the tasks. The forward inference map is produced by calculating the convergence of brain regions most consistently activated by certain cognitive processes. (b) Reverse inference shows that not many DMN regions are specifically associated with these tasks. The reverse inference map is calculated as the likelihood of a search term being used in a study given the presence of reported activation, and it reflects the brain activation specific to a certain cognitive process (Yarkoni et al., 2011). (c) and (d) show that activation of posterior DMN regions is associated with the N-back and RP task (from the HCP database). Warm/cold regions in the brain heatmap indicate higher/lower activity in the difficult condition compared to the easy condition. For panels (a) and (b) standardised Z scores and for panels (c) and (d) T-scores indicating activation strength are provided with colour scales. For highlighting activation in relation to the DMN, 3D renderings of the DMN are shown in shaded grey, on which our activated regions are superimposed. This was constructed by superimposing the Z-score maps (with the cut-off of 3) and T-scores (of

Figure 8: A conceptual predictive model centring at the medial posterior DMN. The medial posterior DMN behaves like a predictive system, with its dorsal part associated with an attentional system (comprising FPCN regions such as the IPS, middle and lateral frontal cortices) and its ventral part associate with a reactive system (comprising regions such as anterior insula) (Tops et al., 2014). The connectivity from each module is derived from our studies, with the pink colour indicating being stronger in difficult conditions, and blue colour indicating being stronger in easy conditions. The (directed) connectivity pattern from our result suggests that external and internal information is exchanged by the reciprocal loop between the vPCu and dPCu. This exchange of information might support the predictive coding theory which emphasises that external information is always inferred (rather than simply being represented from a bottom-up direction) based on an internal belief of the world (prediction).

Figure 7. Illustration of the model structure of the winning DCM model.

Table 1: The N-back and the RP task resulted in the same pattern of PCu fragmentation. The dorsal PCu (dPCu) and ventral PCu (vPCu) were identified as the regions responsive to different cognitive load: the dPCu was activated while the vPCu was deactivated by an increased cognitive demand in difficult versus easy conditions. The N-back task provided a statistically stronger demonstration (larger significant clusters) of this, possibly because the task had more trials i.e. bigger sample size (80 trials in the N-back, vs. 27 in the RP task).

Table 4: Model comparison result suggests that the causal influence from the vPCu to dPCu is modulated in easier conditions and then swapped from the dPCu to vPCu in more difficult conditions. The first 4 rows/aspects of the model structure specified 11 DCM models. The first four DCMs that adopted “one-state”, “deterministic” neural mass model won over the “twostate”, “stochastic” ones, according to the posterior probability at the group level (assuming a fixed factor effect). Among the “one-state”, “deterministic” DCMs, the third model wins over others with consistently higher posterior probability and higher exceedance of model evidence.

Full text

1
A PRECUNEAL CAUSAL LOOP MEDIATES EXTERNAL AND
INTERNAL INFORMATION INTEGRATION IN THE HUMAN BRAIN
D. Lu
1,2,3
, I. Pappas
4
, D. K. Menon
1,2,3
& E. A. Stamatakis
1,2,3
Affiliations:
1
Department of Clinical Neurosciences, University of Cambridge, Addenbrooke’s Hospital, Hills Rd,
CB2 0SP Cambridge, UK.
2
University Division of Anaesthesia, University of Cambridge, Addenbrooke’s Hospital, Hills Rd, CB2
0SP Cambridge.
3
Wolfson Brain Imaging Centre, University of Cambridge, Cambridge Biomedical Campus (Box 65),
CB2, 0QQ, Cambridge, UK.
4
Helen Wills Neuroscience Institute, University of California, Berkeley, CA, 94720, USA.
Corresponding authors. Email addresses: dl577@cam.ac.uk, eas46@cam.ac.uk.
ABSTRACT
Human brains interpret external stimuli based on internal representations. One untested
hypothesis is that the default-mode network (DMN) while responsible for internally
oriented cognition can also encode externally oriented information. The unique
neuroanatomical and functional fingerprint of the posterior part of the DMN supports a
prominent role for the precuneus in this process. By utilising imaging data during two
tasks from 100 participants, we found that the precuneus is functionally divided into
dorsal and ventral subdivisions, each one differentially connecting to internally and
externally oriented networks. The strength and direction of their connectivity is
modulated by task difficulty in a manner dictated by the balance of internal versus
external cognitive demands. Our study provides evidence that the medial posterior part
of the DMN may drive interactions between large-scale networks, potentially allowing
.CC-BY 4.0 International licenseavailable under a
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made
The copyright holder for this preprintthis version posted August 21, 2020. ; https://doi.org/10.1101/2020.08.20.259846doi: bioRxiv preprint

2
access to stored representations for moment to moment interpretation of an ever-
changing environment.
INTRODUCTION
The intrinsic coupling between regions in the human brain (or functional
connectivity/FC) is not random but forms consistent spatial patterns known as Intrinsic
(functional) Connectivity Networks (ICN) (Seeley et al., 2007). Each ICN’s relevance to
cognitive function has been established from activation studies, from which we can infer
what information features are encoded in different networks (Cole et al., 2014).
Interactions between ICNs are thought to be a form of information exchange
serving cognitive demands, although the precise functional role of those interactions
remains an active area of research (Bressler & Menon, 2010). A case in point is the
interaction between the default mode network (DMN) and cognitive control networks
which have been reported to be anti-correlated (Fox et al., 2005) and contraposed in
their cognitive function (Weissman et al., 2006). This view however is increasingly
challenged by accumulating findings. While the majority of DMN studies focus on
resting state, i.e. in the absence of external stimulation, emerging evidence shows that
the DMN is indeed engaged during goal-directed tasks (Elton & Gao, 2015; Spreng et
al., 2014; D. Vatansever et al., 2015; Deniz Vatansever et al., 2015, 2018), as opposed
to being a “resting-state” network.
A conciliatory model that can account for both the internal and external role of
DMN is that of predictive coding. The basic assumption is that conscious processing,
whether externally oriented or not, always entails some form of internal processing.
.CC-BY 4.0 International licenseavailable under a
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made
The copyright holder for this preprintthis version posted August 21, 2020. ; https://doi.org/10.1101/2020.08.20.259846doi: bioRxiv preprint

3
Thus internal and external representations are not dissociated but rather constantly
update each other in a Bayesian fashion (Barrett & Simmons, 2015; Friston, 2012).
Given its multifaceted role in external and internal processing and motivated by
pharmacological and brain injury studies that highlight the DMN’s prominent role in
conscious processing (Liu et al., 2015; Perri et al., 2016; Vanhaudenhuyse et al., 2010),
we hypothesised that the DMN is fundamental when considering the neural instantiation
of such an account.
The DMN, which comprises medial frontal and medial posterior parietal cortices
as well as angular gyri and hippocampus, is neither anatomically nor functionally
homogeneous (Braga et al., 2013; Braga & Buckner, 2017; Kernbach et al., 2018).
Among the DMN regions, the precuneus (PCu/PCC) has attracted significant interest
due to its complex neuroanatomical, metabolic and functional fingerprint (de Pasquale
et al., 2012; Raichle et al., 2001; Spreng et al., 2009; Utevsky et al., 2014). The PCu
has been characterised as the nexus of the DMN’s integrative fingerprint (Utevsky et al.,
2014). It is engaged in a broad range of cognitive tasks, including both internal
representation and externally-oriented, goal-directed tasks (Cavanna & Trimble, 2006;
Fletcher et al., 1995) and its activity/connectivity can discriminate between
conscious/unconscious states (Utevsky et al., 2014). It has exceptionally high metabolic
rate (Raichle et al., 2001) and is suggested to have undergone the biggest brain
morphological expansion through human evolution (Bruner & Iriki, 2016). The PCu is
also a major connectivity hub from a graph-theoretic perspective (P van den Heuvel &
Sporns, 2011; Tomasi & Volkow, 2011; van den Heuvel & Sporns, 2013). Based on its
.CC-BY 4.0 International licenseavailable under a
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made
The copyright holder for this preprintthis version posted August 21, 2020. ; https://doi.org/10.1101/2020.08.20.259846doi: bioRxiv preprint

4
functional features we hypothesised that the PCu may play a key role in integrating
external information with internal representations.
To investigate this claim, we first ascertained the DMN’s involvement in cognitive
tasks by employing a NeuroSynth meta-analytic framework. We then used MRI datasets
(diffusion MRI, resting-state & task-state fMRI) from the Human Connectome Project to
investigate activity as well as functional and structural connectivity of the PCu with
whole-brain ICNs. We found that the dorsal and ventral PCu subdivisions had distinct
activity and connectivity patterns modulated by task difficulty, a factor that influenced a
mirrored interplay between the PCu and internally/externally oriented networks. This
feature of the PCu suggests that it might support the integration between internally and
externally oriented cognitive processes. Moreover, Dynamic Causal Modelling (DCM)
provided evidence for directed couplings between the two PCu subdivisions, hinting at a
combinatorial processing mode where incoming information is associated with internal
representations.
RESULTS
The DMN during tasks: A meta-analytic perspective
We first validated that the DMN is indeed involved during goal-directed tasks, as
findings regarding DMN’s involvement during tasks are still disputed (Fransson, 2006).
We conducted a meta-analysis with the latest NeuroSynth database, using a text-based
filter (“attention* or execut*”) to search for tasks that require either attention or executive
processing or both (since the two cognitive processes are hardly separable in practice),
which yielded 1219 fMRI studies. Using the forward-inference estimation, we found that
.CC-BY 4.0 International licenseavailable under a
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made
The copyright holder for this preprintthis version posted August 21, 2020. ; https://doi.org/10.1101/2020.08.20.259846doi: bioRxiv preprint

5
a large portion of the DMN (1667 voxels) was associated with these tasks (Figure 1a),
with significant clusters (Z > 4) located at the PCu and angular gyrus (AnG). In contrast,
the reverse-inference estimation only revealed 68 voxels in DMN regions (Figure 1b).
We acknowledge that NeuroSynth meta-analyses do not differentiate between
activation and deactivation but based on previous literature which has shown PCu and
AnG involvement in cognitive processing, we believe what we see here is that the tasks
employ posterior DMN regions, yet their activation is so pervasive among all kinds of
tasks that cannot be exclusively associated with the specified goal-directed tasks. We
propose that the meta-analysis indicates a domain-general role for posterior DMN areas
which may serve cognitive demands by providing contextual information.
To investigate the relationship between DMN and other ICNs in more detail
during task execution, we selected two fMRI paradigms (100 young healthy participants)
from the HCP dataset. The tasks we chose were the N-back working memory task and
the Relational Processing (RP) task, which have attention-demanding, goal-directed
features, and engage similar cognitive domains at two difficulty levels (N-back: 2-back >
0-back conditions, RP: relational processing > matching conditions); therefore, the two
tasks afforded us the possibility of inferring the brain’s response to varying cognitive
demands regardless of the specific cognitive content. The merit of using two tasks is to
demonstrate that the DMN’s function is generalisable. As a sanity check for both tasks,
the accuracy rate (N-back task: t = 2.44, p = 0.016; RP task: t = 8.80, p = 1.012e-15)
was significantly higher in the easy than difficult conditions, and reaction times (RT)
were significantly shorter (N-back task: t = 10.58, p < 2.2e-16; RP task: t = 10.02, p <
.CC-BY 4.0 International licenseavailable under a
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made
The copyright holder for this preprintthis version posted August 21, 2020. ; https://doi.org/10.1101/2020.08.20.259846doi: bioRxiv preprint