The human brain is a complex network. An important first step toward understanding the function of such a network is to map its elements and connections, to create a comprehensive structural description of the network architecture. This paper reviews current empirical efforts toward generating a network map of the human brain, the human connectome, and explores how the connectome can provide new insights into the organization of the brain's structural connections and their role in shaping functional dynamics. Network studies of structural connectivity obtained from noninvasive neuroimaging have revealed a number of highly nonrandom network attributes, including high clustering and modularity combined with high efficiency and short path length. The combination of these attributes simultaneously promotes high specialization and high integration within a modular small-world architecture. Structural and functional networks share some of the same characteristics, although their relationship is complex and nonlinear. Future studies of the human connectome will greatly expand our knowledge of network topology and dynamics in the healthy, developing, aging, and diseased brain.

The human connectome: a complex network

After a century of false hopes, recent studies have placed the concept of diaschisis at the centre of the understanding of brain function. Originally, the term 'diaschisis' was coined by von Monakow in 1914 to describe the neurophysiological changes that occur distant to a focal brain lesion. In the following decades, this concept triggered widespread clinical interest in an attempt to describe symptoms and signs that the lesion could not fully explain. However, the first imaging studies, in the late 1970s, only partially confirmed the clinical significance of diaschisis. Focal cortical areas of diaschisis (i.e. focal diaschisis) contributed to the clinical deficits after subcortical but only rarely after cortical lesions. For this reason, the concept of diaschisis progressively disappeared from the mainstream of research in clinical neurosciences. Recent evidence has unexpectedly revitalized the notion. The development of new imaging techniques allows a better understanding of the complexity of brain organization. It is now possible to reliably investigate a new type of diaschisis defined as the changes of structural and functional connectivity between brain areas distant to the lesion (i.e. connectional diaschisis). As opposed to focal diaschisis, connectional diaschisis, focusing on determined networks, seems to relate more consistently to the clinical findings. This is particularly true after stroke in the motor and attentional networks. Furthermore, normalization of remote connectivity changes in these networks relates to a better recovery. In the future, to investigate the clinical role of diaschisis, a systematic approach has to be considered. First, emerging imaging and electrophysiological techniques should be used to precisely map and selectively model brain lesions in human and animals studies. Second, the concept of diaschisis must be applied to determine the impact of a focal lesion on new representations of the complexity of brain organization. As an example, the evaluation of remote changes in the structure of the connectome has so far mainly been tested by modelization of focal brain lesions. These changes could now be assessed in patients suffering from focal brain lesions (i.e. connectomal diaschisis). Finally, and of major significance, focal and non-focal neurophysiological changes distant to the lesion should be the target of therapeutic strategies. Neuromodulation using transcranial magnetic stimulation is one of the most promising techniques. It is when this last step will be successful that the concept of diaschisis will gain all the clinical respectability that could not be obtained in decades of research.

Diaschisis: past, present, future.

Parkinson’s disease is a chronic progressive neurodegenerative disorder characterized by resting tremor, slowness of movements, rigidity, gait disturbance and postural instability. Most investigations on Parkinson’s disease focused on the basal ganglia, whereas the cerebellum has often been overlooked. However, increasing evidence suggests that the cerebellum may have certain roles in the pathophysiology of Parkinson’s disease. Anatomical studies identified reciprocal connections between the basal ganglia and cerebellum. There are Parkinson’s disease–related pathological changes in the cerebellum. Functional or morphological modulations in the cerebellum were detected related to akinesia/rigidity, tremor, gait disturbance, dyskinesia and some non-motor symptoms. It is likely that the major roles of the cerebellum in Parkinson’s disease include pathological and compensatory effects. Pathological changes in the cerebellum might be induced by dopaminergic degeneration, abnormal drives from the basal ganglia and dopaminergic treatment, and may account for some clinical symptoms in Parkinson’s disease. The compensatory effect may help maintain better motor and non-motor functions. The cerebellum is also a potential target for some parkinsonian symptoms. Our knowledge about the roles of the cerebellum in Parkinson’s disease remains limited, and further attention to the cerebellum is warranted.

The cerebellum in Parkinson’s disease

Deficits following stroke are classically attributed to focal damage, but recent evidence suggests a key role of distributed brain network disruption. We measured resting functional connectivity (FC), lesion topography, and behavior in multiple domains (attention, visual memory, verbal memory, language, motor, and visual) in a cohort of 132 stroke patients, and used machine-learning models to predict neurological impairment in individual subjects. We found that visual memory and verbal memory were better predicted by FC, whereas visual and motor impairments were better predicted by lesion topography. Attention and language deficits were well predicted by both. Next, we identified a general pattern of physiological network dysfunction consisting of decrease of interhemispheric integration and intrahemispheric segregation, which strongly related to behavioral impairment in multiple domains. Network-specific patterns of dysfunction predicted specific behavioral deficits, and loss of interhemispheric communication across a set of regions was associated with impairment across multiple behavioral domains. These results link key organizational features of brain networks to brain–behavior relationships in stroke.

https://www.pnas.org/content/pnas/113/30/E4367.full.pdf

Disruptions of network connectivity predict impairment in multiple behavioral domains after stroke

The motor system comprises a network of cortical and subcortical areas interacting via excitatory and inhibitory circuits, thereby governing motor behaviour The balance within the motor network may be critically disturbed after stroke when the lesion either directly affects any of these areas or damages-related white matter tracts A growing body of evidence suggests that abnormal interactions among cortical regions remote from the ischaemic lesion might also contribute to the motor impairment after stroke Here, we review recent studies employing models of functional and effective connectivity on neuroimaging data to investigate how stroke influences the interaction between motor areas and how changes in connectivity relate to impaired motor behaviour and functional recovery Based on such data, we suggest that pathological intra- and inter-hemispheric interactions among key motor regions constitute an important pathophysiological aspect of motor impairment after subcortical stroke We also demonstrate that therapeutic interventions, such as repetitive transcranial magnetic stimulation, which aims to interfere with abnormal cortical activity, may correct pathological connectivity not only at the stimulation site but also among distant brain regions In summary, analyses of connectivity further our understanding of the pathophysiology underlying motor symptoms after stroke, and may thus help to design hypothesis-driven treatment strategies to promote recovery of motor function in patients

http://www.clinicaneurofocus.com.br/files/download/24

Reorganization of cerebral networks after stroke: new insights from neuroimaging with connectivity approaches

Numerous studies argue that cortical reorganization may contribute to the restoration of motor function following stroke. However, the evolution of changes during the post-stroke reorganization has been little studied. This study sought to identify dynamic changes in the functional organization, particularly topological characteristics, of the motor execution network during the stroke recovery process. Ten patients (nine male and one female) with subcortical infarctions were assessed by neurological examination and scanned with resting-state functional magnetic resonance imaging across five consecutive time points in a single year. The motor execution network of each subject was constructed using a functional connectivity matrix between 21 brain regions and subsequently analysed using graph theoretical approaches. Dynamic changes in topological configuration of the network during the process of recovery were evaluated by a mixed model. We found that the motor execution network gradually shifted towards a random mode during the recovery process, which suggests that a less optimized reorganization is involved in regaining function in the affected limbs. Significantly increased regional centralities within the network were observed in the ipsilesional primary motor area and contralesional cerebellum, whereas the ipsilesional cerebellum showed decreased regional centrality. Functional connectivity to these brain regions demonstrated consistent alterations over time. Notably, these measures correlated with different clinical variables, which provided support that the findings may reflect the adaptive reorganization of the motor execution network in stroke patients. In conclusion, the study expands our understanding of the spectrum of changes occurring in the brain after stroke and provides a new avenue for investigating lesion-induced network plasticity.

Dynamic functional reorganization of the motor execution network after stroke

A longitudinal diffusion tensor imaging study on Wallerian degeneration of corticospinal tract after motor pathway stroke.

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Dynamic functional reorganization of the motor execution network after stroke

A longitudinal diffusion tensor imaging study on Wallerian degeneration of corticospinal tract after motor pathway stroke.