The role of the new techniques in the evaluation of the ability to understand and want in patients affected by dementias

Figure 3: Connectivity of Default Mode Network. In yellow the main regions of DMN.In red, green, blu the connectivity among regions chromatically codified by direction of structural crossing (xyz → red-green-blu).

Activation and deactivation of DMN

The default mode network (DMN) comprises defined brain regions contributing to internally-directed thought processes. Reductions in task-induced deactivation in the DMN have been associated with increasing age and poorer executive task performance, but factors underlying these functional changes remain unclear (Brown, 2018).

DMN is a distributed network of brain regions more active during rest than during performance of many attention-demanding tasks and characterized by a high degree of functional connectivity (i.e., temporal correlations between brain regions). Functional magnetic resonance imaging studies have revealed that the DMN in the healthy brain is associated with stimulus-independent thought and self-reflection and that greater suppression of the DMN is associated with better performance on attention-demanding tasks  (Whitfield-Gabrieli, 2012).

Human cognition is flexible, enabling us to select appropriate information from memory, according to current goals. Multiple-demand (MD) cortex, which overlaps with frontal-parietal control network (FPCN) and dorsal attention network (DAN), has an established role in cognitive flexibility (Duncan, 2010), showing stronger responses in more demanding conditions across tasks (Fedorenko et al., 2013; Turnbull et al., 2019a, Turnbull et al., 2019b) and activation patterns that can classify task-critical details in an adaptive fashion (Erez and Duncan, 2015; Cole et al., 2016; Bracci et al., 2017;  Qiao et al., 2017). However, the role of other heteromodal brain regions, such as regions of default mode network (DMN), is more poorly understood ( Wang, 2021).

The default mode network (DMN) is a set of widely distributed brain regions in the parietal, temporal and frontal cortex. These regions often show reductions in activity during attention-demanding tasks but increase their activity across multiple forms of complex cognition, many of which are linked to memory or abstract thought. Within the cortex, the DMN has been shown to be located in regions furthest away from those contributing to sensory and motor systems. Here, several authors [Smallwood et al, 2021] consider how their knowledge of the topographic characteristics of the DMN can be leveraged to better understand how this network contributes to cognition and behaviour. And cognition and behaviour are the most important task to study in people accused of a crimen, in order to understand their ability to understand and will what they have done.

Pathophysiology of DSM (Wang 2011 and  Wang 2021)

Wang (2011) used a semantic feature-matching task combined with multivoxel pattern decoding to test contrasting accounts of the role of the default mode network (DMN) in cognitive flexibility. By one view, DMN and multiple-demand cortex have opposing roles in cognition, with DMN and multiple-demand regions within the dorsal attention network (DAN) supporting internal and external cognition, respectively. Consequently, while multiple-demand regions can decode current goal information, semantically relevant DMN regions might decode conceptual similarity regardless of task demands. Alternatively, DMN regions, like multiple-demand cortex, might show sensitivity to changing task demands, since both networks dynamically alter their patterns of connectivity depending on the context. This task required human participants (any sex) to integrate conceptual knowledge with changing task goals, such that successive decisions were based on different features of the items (color, shape, and size). This allowed Wang to simultaneously decode semantic category and current goal information using whole-brain searchlight decoding. As expected, multiple-demand cortex, including DAN and frontoparietal control network, represented information about currently relevant conceptual features. Similar decoding results were found in DMN, including in angular gyrus and posterior cingulate cortex, indicating that DMN and multiple-demand regions can support the same function rather than being strictly competitive. Semantic category could be decoded in lateral occipital cortex independently of task demands, but not in most regions of DMN. Conceptual information related to the current goal dominates the multivariate response within DMN, which supports flexible retrieval by modulating its response to suit the task demands, alongside regions of multiple-demand cortex. Wang tested contrasting accounts of default mode network (DMN) function using multivoxel pattern analysis. By one view, semantically relevant parts of DMN represent conceptual similarity, regardless of task context. By an alternative view, DMN tracks changing task demands. This semantic feature-matching task required participants to integrate conceptual knowledge with task goals, such that successive decisions were based on different features of the items. Wang demonstrate that DMN regions can decode the current goal, as it is applied, alongside multiple-demand regions traditionally associated with cognitive control, speaking to how DMN supports flexible cognition (Wang, 2021).

DMN and DAN are proposed to subserve internally and externally directed cognition, respectively, and functionally couple with different subsystems of FPCN (Spreng et al., 2010, Spreng et al. 2013; Dixon et al., 2018). DMN is highly heteromodal and is thought to support information integration (Simony et al., 2016;Lanzoni et al, 2020), which is relevant to both long-term episodic memory (Sestieri et al., 2011) and semantic cognition (Binder and Desai, 2011; Wirth et al., 2011; Krieger-Redwood et al., 2016). Semantically relevant DMN regions, including left angular gyrus (AG) and lateral temporal cortex, show less deactivation, relative to rest, when semantic and nonsemantic tasks are compared (Binder et al., 1999, Binder et al. 2009; Humphreys et al., 2015), even when task difficulty is taken into account (Binder et al., 2005; Seghier et al., 2010; Murphy et al., 2018). These observations suggest that DMN might support similarity structures in long-term memory, such as global conceptual similarity (Murphy et al., 2017; Wang et al., 2020), as well as goal information when this information is retrieved from memory.

Recent data on DSM in brain organization (Wang, 2020)

Contemporary accounts of brain organization suggest that neural function is organized along a connectivity gradient from unimodal regions of sensorimotor cortex, through executive regions to transmodal default mode network. Wang’s team examined whether this graded view of neural organization helps to explain how decision-making changes across situations that vary in their alignment with long-term knowledge. They used a semantic judgment task, which parametrically varied the global semantic similarity of items within a feature matching task to create a ‘task gradient’, from conceptual combinations that were highly overlapping in long-term memory to trials that only shared the goal-relevant feature. They found the brain’s response to the task gradient varied systematically along the connectivity gradient, with the strongest response in default mode network when the probe and target items were highly overlapping conceptually. This graded functional change was seen in multiple brain regions and within individual brains, and was not readily explained by task difficulty. Moreover, the gradient captured the spatial layout of networks involved in semantic processing, providing an organizational principle for controlled semantic cognition across the cortex. In this way, the cortex is organized to support semantic decision-making in both highly familiar and less familiar situations (35Wang, 2020).

DSM in Neuropsychiatric disorders, often cause of crimen (Whitfield-Gabrieli, 2012).

Neuropsychiatric disorders are associated with abnormal function of the default mode network (DMN), a distributed network of brain regions more active during rest than during performance of many attention-demanding tasks and characterized by a high degree of functional connectivity (i.e., temporal correlations between brain regions). Functional magnetic resonance (fMRI) imaging studies have revealed that the DMN in the healthy brain is associated with stimulus-independent thought and self-reflection and that greater suppression of the DMN is associated with better performance on attention-demanding tasks. In schizophrenia and depression, the DMN is often found to be hyperactivated and hyperconnected. In schizophrenia this may relate to overly intensive self-reference and impairments in attention and working memory. In depression, DMN hyperactivity may be related to negative rumination. These findings are considered in terms of what is known about psychological functions supported by the DMN, and alteration of the DMN in other neuropsychiatric disorders (Whitfield-Gabrieli, 2012).

DMN alteration in Dementia (Browun, 2018) – [fig. 4]

Brown (362018) investigated contributions of white matter (WM) microstructure, WM hyperintensities (WMH) and Alzheimer's pathology to age-related alterations in DMN function. Thirty-five cognitively normal older adults and 29 younger adults underwent working memory task fMRI and diffusion tensor imaging. In the older adults, it was measured cerebrospinal fluid tau and Aβ42 (markers of AD pathology), and WMH on FLAIR imaging (marker of cerebrovascular disease). It was identified a set of regions showing DMN deactivation and a set of inter-connecting WM tracts (DMN-WM) common to both age groups. There were negative associations between DMN deactivation and task performance in older adults, consistent with previous studies. Decreased DMN deactivation was associated with AD pathology and WM microstructure but not with WMH volume. Mediation analyses showed that WM microstructure mediated declines in DMN deactivation associated with both aging and AD pathology. Together these results suggest that AD pathology may exert a “second-hit” on WM microstructure, over-and-above the effects of age, both contributing to diminished DMN deactivation in older adults.