Police, ambulance and psychiatric co-response versus usual care for mental health and suicide emergency callouts: A quasi-experimental study.

OBJECTIVE: Mental health-related calls to emergency services made via 111 (New Zealand) or 000 (Australia) often represent critical junctures for the person in crisis. Traditionally, police, ambulance and mental health services work separately to manage such emergencies. Sequential agency responses may be protracted and cause escalation. This study tests multi-agency co-response aiming for more integrated, faster, safer and less coercive management of mental health crises. METHODS: Immediate and 1-month outcomes of mental health emergency calls made to police and ambulance were compared according to whether they occurred on days with co-response availability. Outcomes measured included emergency department admission and waiting times, psychiatric admissions, compulsory treatment, use of force, detention in police cells and the time to resolution of the event. Relative risk estimates were constructed. RESULTS: A total 1273 eligible mental health emergency callouts occurred between March 2020 and March 2021 (38% coded 'mental health' emergencies, 48% suicide risk and 14% as 'other'), 881 on days with co-response availability and 392 on days without. Co-response interventions were resolved faster and were more likely to be community-based. Fewer than one-third (32%) led to emergency department admissions, compared with close to half (45%) on days without co-response (risk ratio: 0.7 [0.6, 0.8]). In the following month, the number of emergency department and mental health admissions reduced (p < 0.01 and 0.05, respectively). There were no statistically significant differences in use of force and few people were detained in police custody. CONCLUSION: Co-response intervention increased the likelihood of mental health crises being resolved in the community and reduced hospitalisations. Benefits were sustained at 1 month.

Relating Cognition to both Brain Structure and Function: A Systematic Review of Methods.

Introduction: Cognitive neuroscience explores the mechanisms of cognition by studying its structural and functional brain correlates. Many studies have combined structural and functional neuroimaging techniques to uncover the complex relationship between them. In this study, we report the first systematic review that assesses how information from structural and functional neuroimaging methods can be integrated to investigate the brain substrates of cognition. Procedure: Web of Science and Scopus databases were searched for studies of healthy young adult populations that collected cognitive data and structural and functional neuroimaging data. Results: Five percent of screened studies met all inclusion criteria. Next, 50% of included studies related cognitive performance to brain structure and function without quantitative analysis of the relationship. Finally, 31% of studies formally integrated structural and functional brain data. Overall, many studies consider either structural or functional neural correlates of cognition, and of those that consider both, they have rarely been integrated. We identified four emergent approaches to the characterization of the relationship between brain structure, function, and cognition; comparative, predictive, fusion, and complementary. Discussion: We discuss the insights provided in each approach about the relationship between brain structure and function and how it impacts cognitive performance. In addition, we discuss how authors can select approaches to suit their research questions. Impact statement The relationship between structural and functional brain networks and their relationship to cognition is a matter of current investigations. This work surveys how researchers have studied the relationship between brain structure and function and its impact on cognitive function in healthy adult populations. We review four emergent approaches of quantitative analysis of this multivariate problem; comparative, predictive, fusion, and complementary. We explain the characteristics of each approach, discuss the insights provided in each approach, and how authors can combine approaches to suit their research questions.

Combination of structural and functional connectivity explains unique variation in specific domains of cognitive function.

The relationship between structural and functional brain networks has been characterised as complex: the two networks mirror each other and show mutual influence but they also diverge in their organisation. This work explored whether a combination of structural and functional connectivity can improve the fit of regression models of cognitive performance. Principal Component Analysis (PCA) was first applied to cognitive data from the Human Connectome Project to identify latent cognitive components: Executive Function, Self-regulation, Language, Encoding and Sequence Processing. A Principal Component Regression approach with embedded Step-Wise Regression (SWR-PCR) was then used to fit regression models of each cognitive domain based on structural (SC), functional (FC) or combined structural-functional (CC) connectivity. Executive Function was best explained by the CC model. Self-regulation was equally well explained by SC and FC. Language was equally well explained by CC and FC models. Encoding and Sequence Processing were best explained by SC. Evaluation of out-of-sample models' skill via cross-validation showed that SC, FC and CC produced generalisable models of Language performance. SC models performed most effectively at predicting Language performance in unseen sample. Executive Function was most effectively predicted by SC models, followed only by CC models. Self-regulation was only effectively predicted by CC models and Sequence Processing was only effectively predicted by FC models. The present study demonstrates that integrating structural and functional connectivity can help explaining cognitive performance, but that the added explanatory value (in-sample) may be domain-specific and can come at the expense of reduced generalisation performance (out-of-sample).

A tutorial and tool for exploring feature similarity gradients with MRI data.

There has been an increasing interest in examining organisational principles of the cerebral cortex (and subcortical regions) using different MRI features such as structural or functional connectivity. Despite the widespread interest, introductory tutorials on the underlying technique targeted for the novice neuroimager are sparse in the literature. Articles that investigate various "neural gradients" (for example based on region studied "cortical gradients," "cerebellar gradients," "hippocampal gradients" etc … or feature of interest "functional gradients," "cytoarchitectural gradients," "myeloarchitectural gradients" etc …) have increased in popularity. Thus, we believe that it is opportune to discuss what is generally meant by "gradient analysis". We introduce basics concepts in graph theory, such as graphs themselves, the degree matrix, and the adjacency matrix. We discuss how one can think about gradients of feature similarity (the similarity between timeseries in fMRI, or streamline in tractography) using graph theory and we extend this to explore such gradients across the whole MRI scale; from the voxel level to the whole brain level. We proceed to introduce a measure for quantifying the level of similarity in regions of interest. We propose the term "the Vogt-Bailey index" for such quantification to pay homage to our history as a brain mapping community. We run through the techniques on sample datasets including a brain MRI as an example of the application of the techniques on real data and we provide several appendices that expand upon details. To maximise intuition, the appendices contain a didactic example describing how one could use these techniques to solve a particularly pernicious problem that one may encounter at a wedding. Accompanying the article is a tool, available in both MATLAB and Python, that enables readers to perform the analysis described in this article on their own data. We refer readers to the graphical abstract as an overview of the analysis pipeline presented in this work.

The Graded Change in Connectivity across the Ventromedial Prefrontal Cortex Reveals Distinct Subregions.

The functional heterogeneity of the ventromedial prefrontal cortex (vmPFC) suggests it may include distinct functional subregions. To date these have not been well elucidated. Regions with differentiable connectivity (and as a result likely dissociable functions) may be identified using emergent data-driven approaches. However, prior parcellations of the vmPFC have only considered hard splits between distinct regions, although both hard and graded connectivity changes may exist. Here we determine the full pattern of change in structural and functional connectivity across the vmPFC for the first time and extract core distinct regions. Both structural and functional connectivity varied along a dorsomedial to ventrolateral axis from relatively dorsal medial wall regions to relatively lateral basal orbitofrontal cortex. The pattern of connectivity shifted from default mode network to sensorimotor and multimodal semantic connections. This finding extends the classical distinction between primate medial and orbital regions by demonstrating a similar gradient in humans for the first time. Additionally, core distinct regions in the medial wall and orbitofrontal cortex were identified that may show greater correspondence to functional differences than prior hard parcellations. The possible functional roles of the orbitofrontal cortex and medial wall are discussed.

A structural connectivity convergence zone in the ventral and anterior temporal lobes: Data-driven evidence from structural imaging.

The hub-and-spoke model of semantic cognition seeks to reconcile embodied views of a fully distributed semantic network with patient evidence, primarily from semantic dementia, who demonstrate modality-independent conceptual deficits associated with atrophy centred on the ventrolateral anterior temporal lobe. The proponents of this model have recently suggested that the temporal cortex is a graded representational space where concepts become less linked to a specific modality as they are processed farther away from primary and secondary sensory cortices and towards the ventral anterior temporal lobe. To explore whether there is evidence that the connectivity patterns of the temporal lobe converge in its ventral anterior end the current study uses three dimensional Laplacian eigenmapping, a technique that allows visualisation of similarity in a low dimensional space. In this space similarity is encoded in terms of distances between data points. We found that the ventral and anterior temporal lobe is in a unique position of being at the centre of mass of the data points within the connective similarity space. This can be interpreted as the area where the connectivity profiles of all other temporal cortex voxels converge. This study is the first to explicitly investigate the pattern of connectivity and thus provides the missing link in the evidence that the ventral anterior temporal lobe can be considered a multi-modal graded hub.

Exploring distinct default mode and semantic networks using a systematic ICA approach.

Resting-state networks (RSNs; groups of regions consistently co-activated without an explicit task) are hugely influential in modern brain research. Despite this popularity, the link between specific RSNs and their functions remains elusive, limiting the impact on cognitive neuroscience (where the goal is to link cognition to neural systems). Here we present a series of logical steps to formally test the relationship between a coherent RSN with a cognitive domain. This approach is applied to a challenging and significant test-case; extracting a recently-proposed semantic RSN, determining its relation with a well-known RSN, the default mode network (DMN), and assessing their roles in semantic cognition. Results showed the DMN and semantic network are two distinct coherent RSNs. Assessing the cognitive signature of these spatiotemporally coherent networks directly (and therefore accounting for overlapping networks) showed involvement of the proposed semantic network, but not the DMN, in task-based semantic cognition. Following the steps presented here, researchers could formally test specific hypotheses regarding the function of RSNs, including other possible functions of the DMN.

An emergent functional parcellation of the temporal cortex.

The temporal lobe has been associated with various cognitive functions which include memory, auditory cognition and semantics. However, at a higher level of conceptualisation, all of the functions associated with the temporal lobe can be considered as lying along one major axis; from modality-specific to modality-general processing. This paper used a spectral reordering technique on resting-state and task-based functional data to extract the major organisational axis of the temporal lobe in a bottom-up, data-driven fashion. Independent parcellations were performed on resting-state scans from 71 participants and active semantic task scans from 23 participants acquired using dual echo gradient echo planar imaging in order to preserve signal in inferior temporal cortex. The resulting organisational axis was consistent (over dataset and hemisphere) and progressed from superior temporal gyrus and posterior inferior temporal cortex to ventrolateral anterior temporal cortex. A hard parcellation separated a posterior (superior temporal and posterior fusiform and inferior temporal gyri) and an anterior cluster (ventrolateral anterior temporal lobe). The functional connectivity of the hard clusters supported the hypothesis that the connectivity gradient separated modality-specific and modality-general regions. This hypothesis was then directly tested by performing a VOI analysis upon an independent semantic task-based data set including auditory and visually presented stimuli. This confirmed that the ventrolateral anterior aspects of the temporal lobe are associated with modality-general processes whilst posterior and superior aspects are specific to certain modalities, with the posterior inferior subregions involved in visual processes and superior regions involved in audition.

A graded tractographic parcellation of the temporal lobe.

The temporal lobe has been implicated in multiple cognitive domains through lesion studies as well as cognitive neuroimaging research. There has been a recent increased interest in the structural and connective architecture that underlies these functions. However there has not yet been a comprehensive exploration of the patterns of connectivity that appear across the temporal lobe. This article uses a data driven, spectral reordering approach in order to understand the general axes of structural connectivity within the temporal lobe. Two important findings emerge from the study. Firstly, the temporal lobe's overarching patterns of connectivity are organised along two key structural axes: medial to lateral and anteroventral to posterodorsal, mirroring findings in the functional literature. Secondly, the connective organisation of the temporal lobe is graded and transitional; this is reminiscent of the original work of 19th Century neuroanatomists, who posited the existence of some regions which transitioned between one another in a graded fashion. While regions with unique connectivity exist, the boundaries between these are not always sharp. Instead there are zones of graded connectivity reflecting the influence and overlap of shared connectivity.

The structural connectivity of higher order association cortices reflects human functional brain networks.

Human higher cognition arises from the main tertiary association cortices including the frontal, temporal and parietal lobes. Many studies have suggested that cortical functions must be shaped or emerge from the pattern of underlying physical (white matter) connectivity. Despite the importance of this hypothesis, there has not been a large-scale analysis of the white-matter connectivity within and between these associative cortices. Thus, we explored the pattern of intra- and inter-lobe white matter connectivity between multiple areas defined in each lobe. We defined 43 regions of interest on the lateral associative cortex cytoarchitectonically (6 regions of interest - ROIs in the frontal lobe and 17 ROIs in the parietal lobe) and anatomically (20 ROIs in the temporal lobe) on individuals' native space. The results demonstrated that intra-region connectivity for all 3 lobes was dense and graded generally. In contrary, the inter-lobe connectivity was relatively discrete and regionally specific such that only small sub-regions exhibited long-range connections to another lobe. The long-range connectivity was mediated by 6 major associative white matter tracts, consistent with the notion that these higher cognitive functions arises from brain-wide distributed connectivity. Using graph-theory network analysis we revealed five physically-connected sub-networks, which correspond directly to five known functional networks. This study provides strong and direct evidence that core functional brain networks mirror the brain's structural connectivity.

The tract terminations in the temporal lobe: Their location and associated functions.

Temporal lobe networks are associated with multiple cognitive domains. Despite an upsurge of interest in connectional neuroanatomy, the terminations of the main fibre tracts in the human brain are yet to be mapped. This information is essential given that neurological, neuroanatomical and computational accounts expect neural functions to be strongly shaped by the pattern of white-matter connections. This paper uses a probabilistic tractography approach to identify the main cortical areas that contribute to the major temporal lobe tracts. In order to associate the tract terminations to known functional domains of the temporal lobe, eight automated meta-analyses were performed using the Neurosynth database. Overlaps between the functional regions highlighted by the meta-analyses and the termination maps were identified in order to investigate the functional importance of the tracts of the temporal lobe. The termination maps are made available in the Supplementary Materials of this article for use by researchers in the field.

Taking Sides: An Integrative Review of the Impact of Laterality and Polarity on Efficacy of Therapeutic Transcranial Direct Current Stimulation for Anomia in Chronic Poststroke Aphasia.

Anomia is a frequent and persistent symptom of poststroke aphasia, resulting from damage to areas of the brain involved in language production. Cortical neuroplasticity plays a significant role in language recovery following stroke and can be facilitated by behavioral speech and language therapy. Recent research suggests that complementing therapy with neurostimulation techniques may enhance functional gains, even amongst those with chronic aphasia. The current review focuses on the use of transcranial Direct Current Stimulation (tDCS) as an adjunct to naming therapy for individuals with chronic poststroke aphasia. Our survey of the literature indicates that combining therapy with anodal (excitatory) stimulation to the left hemisphere and/or cathodal (inhibitory) stimulation to the right hemisphere can increase both naming accuracy and speed when compared to the effects of therapy alone. However, the benefits of tDCS as a complement to therapy have not been yet systematically investigated with respect to site and polarity of stimulation. Recommendations for future research to help determine optimal protocols for combined therapy and tDCS are outlined.

Transport for language south of the Sylvian fissure: The routes and history of the main tracts and stations in the ventral language network.

It is now ten years since a 'ventral language pathway' was demonstrated in vivo in the human brain. In the intervening decade, this result has been replicated and expanded to include multiple possible pathways and functions. Despite this considerable level of research interest, age-old debates regarding the origin, course, termination and, indeed, the very existence of the tracts identified still remain. The current review examines four major tracts associated with the ventral 'semantic' language network, with the aim of elucidating and clarifying their structural and functional roles. Historical and modern conceptualisations of the tracts' neuroanatomical origins and terminations will be discussed, and key discrepancies and debates examined. It is argued that much of the controversy regarding the language pathways has resulted from inconsistencies in terminology, and the lack of a white matter 'lingua franca'.

Mismatch negativity (MMN) reveals inefficient auditory ventral stream function in chronic auditory comprehension impairments.

BACKGROUND: Auditory discrimination is significantly impaired in Wernicke's aphasia (WA) and thought to be causatively related to the language comprehension impairment which characterises the condition. This study used mismatch negativity (MMN) to investigate the neural responses corresponding to successful and impaired auditory discrimination in WA. METHODS: Behavioural auditory discrimination thresholds of consonant-vowel-consonant (CVC) syllables and pure tones (PTs) were measured in WA (n = 7) and control (n = 7) participants. Threshold results were used to develop multiple deviant MMN oddball paradigms containing deviants which were either perceptibly or non-perceptibly different from the standard stimuli. MMN analysis investigated differences associated with group, condition and perceptibility as well as the relationship between MMN responses and comprehension (within which behavioural auditory discrimination profiles were examined). RESULTS: MMN waveforms were observable to both perceptible and non-perceptible auditory changes. Perceptibility was only distinguished by MMN amplitude in the PT condition. The WA group could be distinguished from controls by an increase in MMN response latency to CVC stimuli change. Correlation analyses displayed a relationship between behavioural CVC discrimination and MMN amplitude in the control group, where greater amplitude corresponded to better discrimination. The WA group displayed the inverse effect; both discrimination accuracy and auditory comprehension scores were reduced with increased MMN amplitude. In the WA group, a further correlation was observed between the lateralisation of MMN response and CVC discrimination accuracy; the greater the bilateral involvement the better the discrimination accuracy. CONCLUSIONS: The results from this study provide further evidence for the nature of auditory comprehension impairment in WA and indicate that the auditory discrimination deficit is grounded in a reduced ability to engage in efficient hierarchical processing and the construction of invariant auditory objects. Correlation results suggest that people with chronic WA may rely on an inefficient, noisy right hemisphere auditory stream when attempting to process speech stimuli.

Using in vivo probabilistic tractography to reveal two segregated dorsal 'language-cognitive' pathways in the human brain.

Primate studies have recently identified the dorsal stream as constituting multiple dissociable pathways associated with a range of specialized cognitive functions. To elucidate the nature and number of dorsal pathways in the human brain, the current study utilized in vivo probabilistic tractography to map the structural connectivity associated with subdivisions of the left supramarginal gyrus (SMG). The left SMG is a prominent region within the dorsal stream, which has recently been parcellated into five structurally-distinct regions which possess a dorsal-ventral (and rostral-caudal) organisation, postulated to reflect areas of functional specialisation. The connectivity patterns reveal a dissociation of the arcuate fasciculus into at least two segregated pathways connecting frontal-parietal-temporal regions. Specifically, the connectivity of the inferior SMG, implicated as an acoustic-motor speech interface, is carried by an inner/ventro-dorsal arc of fibres, whilst the pathways of the posterior superior SMG, implicated in object use and cognitive control, forms a parallel outer/dorso-dorsal crescent.

Interaction between dorsal and ventral processing streams: where, when and how?

The execution of complex visual, auditory, and linguistic behaviors requires a dynamic interplay between spatial ('where/how') and non-spatial ('what') information processed along the dorsal and ventral processing streams. However, while it is acknowledged that there must be some degree of interaction between the two processing networks, how they interact, both anatomically and functionally, is a question which remains little explored. The current review examines the anatomical, temporal, and behavioral evidence regarding three potential models of dual stream interaction: (1) computations along the two pathways proceed independently and in parallel, reintegrating within shared target brain regions; (2) processing along the separate pathways is modulated by the existence of recurrent feedback loops; and (3) information is transferred directly between the two pathways at multiple stages and locations along their trajectories.

Connectivity-based structural and functional parcellation of the human cortex using diffusion imaging and tractography.

The parcellation of the cortex via its anatomical properties has been an important research endeavor for over a century. To date, however, a universally accepted parcellation scheme for the human brain still remains elusive. In the current review, we explore the use of in vivo diffusion imaging and white matter tractography as a non-invasive method for the structural and functional parcellation of the human cerebral cortex, discussing the strengths and limitations of the current approaches. Cortical parcellation via white matter connectivity is based on the premise that, as connectional anatomy determines functional organization, it should be possible to segregate functionally-distinct cortical regions by identifying similarities and differences in connectivity profiles. Recent studies have provided initial evidence in support of the efficacy of this connectional parcellation methodology. Such investigations have identified distinct cortical subregions which correlate strongly with functional regions identified via fMRI and meta-analyses. Furthermore, a strong parallel between the cortical regions defined via tractographic and more traditional cytoarchitectonic parcellation methods has been observed. However, the degree of correspondence and relative functional importance of cytoarchitectonic- versus connectivity-derived parcellations still remains unclear. Diffusion tractography remains one of the only methods capable of visualizing the structural networks of the brain in vivo. As such, it is of vital importance to continue to improve the accuracy of the methodology and to extend its potential applications in the study of cognition in neurological health and disease.

The variation of function across the human insula mirrors its patterns of structural connectivity: evidence from in vivo probabilistic tractography.

The human insula is a functionally complex yet poorly understood region of the cortex, implicated in a wide range of cognitive, motor, emotion and somatosensory activity. To elucidate the functional role of the insula, the current study used in vivo probabilistic tractography to map the structural connectivity of seven anatomically-defined insular subregions. The connectivity patterns identified reveal two complementary insular networks connected via a dual route architecture, and provide key insights about the neural basis of the numerous functions ascribed to this area. Specifically, anterior-most insular regions were associated with a ventrally-based network involving orbital/inferior frontal and anterior/polar temporal regions, forming part of a key emotional salience and cognitive control network associated with the implementation of goal-directed behavior. The posterior and dorsal-middle insular regions were associated with a network focused on posterior and (to a lesser extent) anterior temporal regions via both dorsal and ventral pathways. This is consistent with the involvement of the insula in sound-to-speech transformations, with an implicated role in the temporal resolution, sequencing, and feedback processes crucial for auditory and motor processing, and the monitoring and adjustment of expressive performance.

Asyntactic comprehension, working memory, and acute ischemia in Broca's area versus angular gyrus.

We evaluated sentence comprehension of variety of sentence constructions and components of short-term memory (STM) in 53 individuals with acute ischemic stroke, to test some current hypotheses about the role of Broca's area in these tasks. We found that some patients show structure-specific, task-independent deficits in sentence comprehension, with chance level of accuracy on passive reversible sentences, more impaired comprehension of object-cleft than subject-cleft sentences, and more impaired comprehension of reversible than irreversible sentences in both sentence-picture matching and enactment tasks. In a dichotomous analysis, this pattern of "asyntactic comprehension" was associated with dysfunctional tissue in left angular gyrus, rather than dysfunctional tissue in Broca's area as previously proposed. Tissue dysfunction in left Brodmann area (BA) 44, part of Broca's area, was associated with phonological STM impairment defined by forward digit span≤4. Verbal working memory (VWM) defined by backward digit span≤2 was associated with tissue dysfunction left premotor cortex (BA 6). In a continuous analysis, patients with acute ischemia in left BA 44 were impaired in phonological STM. Patients with ischemia in left BA 45 and BA 6 were impaired in passive, reversible sentences, STM, and VWM. Patients with ischemia in left BA 39 were impaired in passive reversible sentences, object-cleft sentences, STM, and VWM. Therefore, various components of working memory seem to depend on a network of brain regions that include left angular gyrus and posterior frontal cortex (BA 6, 44, 45); left BA 45 and angular gyrus (BA 39) may have additional roles in comprehension of syntax such as thematic role checking.