T J van Hartevelt

Neural plasticity in human brain connectivity: the effects of long term deep brain stimulation of the subthalamic nucleus in Parkinson's disease

Background Positive clinical outcomes are now well established for deep brain stimulation, but little is known about the effects of long-term deep brain stimulation on brain structural and functional connectivity. Here, we used the rare opportunity to acquire pre- and postoperative diffusion tensor imaging in a patient undergoing deep brain stimulation in bilateral subthalamic nuclei for Parkinson’s Disease. This allowed us to analyse the differences in structural connectivity before and after deep brain stimulation. Further, a computational model of spontaneous brain activity was used to estimate the changes in functional connectivity arising from the specific changes in structural connectivity. Results We found significant localised structural changes as a result of long-term deep brain stimulation. These changes were found in sensory-motor, prefrontal/limbic, and olfactory brain regions which are known to be affected in Parkinson’s Disease. The nature of these changes was an increase of nodal efficiency in most areas and a decrease of nodal efficiency in the precentral sensory-motor area. Importantly, the computational model clearly shows the impact of deep brain stimulation-induced structural alterations on functional brain changes, which is to shift the neural dynamics back towards a healthy regime. The results demonstrate that deep brain stimulation in Parkinson’s Disease leads to a topological reorganisation towards healthy bifurcation of the functional networks measured in controls, which suggests a potential neural mechanism for the alleviation of symptoms. Conclusions The findings suggest that long-term deep brain stimulation has not only restorative effects on the structural connectivity, but also affects the functional connectivity at a global level. Overall, our results support causal changes in human neural plasticity after long-term deep brain stimulation and may help to identify the underlying mechanisms of deep brain stimulation.

Deep brain stimulation of the anterior cingulate cortex: targeting the affective component of chronic pain.

Deep brain stimulation (DBS) has shown promise for relieving nociceptive and neuropathic symptoms of refractory chronic pain. We assessed the efficacy of a new target for the affective component of pain, the anterior cingulate cortex (ACC). A 49-year-old man with neuropathic pain underwent bilateral ACC DBS. Patient-reported outcome measures were collected before and 2 years after surgery using a Visual Analogue Scale, Short-Form 36 quality of life survey, McGill pain questionnaire, EuroQol-5D questionnaires (EQ-5D; Health State) and neuropsychological assessments. The patient improved with DBS. Two years after surgery, the Visual Analogue Scale decreased from 6.7 to 3.0, McGill pain questionnaire improved by 42% and EQ-5D Health State increased by 150%. Stimulating the ACC at 130 Hz, 330 µs and 3 V facilitated neuropathic pain relief. The DBS remained efficacious during the 2-year follow-up period. Affective ACC DBS can relieve chronic neuropathic pain refractory to pharmacotherapy and restore quality of life.

Post-traumatic stress influences the brain even in the absence of symptoms: A systematic, quantitative meta-analysis of neuroimaging studies

Stress affects brain function, and may lead to post-traumatic stress disorder (PTSD). Considerable empirical data for the neurobiology of PTSD has been derived from neuroimaging studies, although findings have proven inconsistent. We used an activation likelihood estimation analysis to explore differences in brain activity between adults with and without PTSD in response to affective stimuli. We separated studies by type of control group: trauma-exposed and trauma-naïve. This revealed distinct patterns of differences in functional activity. Compared to trauma-exposed controls, regions of the basal ganglia were differentially active in PTSD; whereas the comparison with trauma-naïve controls revealed differential involvement in the right anterior insula, precuneus, cingulate and orbitofrontal cortices known to be involved in emotional regulation. Changes in activity in the amygdala and parahippocampal cortex distinguished PTSD from both control groups. Results suggest that trauma has a measurable, enduring effect upon the functional dynamics of the brain, even in individuals who experience trauma but do not develop PTSD. These findings contribute to the understanding of whole-brain network activity following trauma, and its transition to clinical PTSD.

How structure sculpts function: Unveiling the contribution of anatomical connectivity to the brain's spontaneous correlation structure

Intrinsic brain activity is characterized by highly organized co-activations between different regions, forming clustered spatial patterns referred to as resting-state networks. The observed co-activation patterns are sustained by the intricate fabric of millions of interconnected neurons constituting the brains wiring diagram. However, as for other real networks, the relationship between the connectional structure and the emergent collective dynamics still evades complete understanding. Here, we show that it is possible to estimate the expected pair-wise correlations that a network tends to generate thanks to the underlying path structure. We start from the assumption that in order for two nodes to exhibit correlated activity, they must be exposed to similar input patterns from the entire network. We then acknowledge that information rarely spreads only along a unique route but rather travels along all possible paths. In real networks, the strength of local perturbations tends to decay as they propagate away from the sources, leading to a progressive attenuation of the original information content and, thus, of their influence. Accordingly, we define a novel graph measure, topological similarity, which quantifies the propensity of two nodes to dynamically correlate as a function of the resemblance of the overall influences they are expected to receive due to the underlying structure of the network. Applied to the human brain, we find that the similarity of whole-network inputs, estimated from the topology of the anatomical connectome, plays an important role in sculpting the backbone pattern of time-average correlations observed at rest.

Evidence from a rare case study for Hebbian-like changes in structural connectivity induced by long-term deep brain stimulation

It is unclear whether Hebbian-like learning occurs at the level of long-range white matter connections in humans, i.e., where measurable changes in structural connectivity (SC) are correlated with changes in functional connectivity. However, the behavioral changes observed after deep brain stimulation (DBS) suggest the existence of such Hebbian-like mechanisms occurring at the structural level with functional consequences. In this rare case study, we obtained the full network of white matter connections of one patient with Parkinson’s disease (PD) before and after long-term DBS and combined it with a computational model of ongoing activity to investigate the effects of DBS-induced long-term structural changes. The results show that the long-term effects of DBS on resting-state functional connectivity is best obtained in the computational model by changing the structural weights from the subthalamic nucleus (STN) to the putamen and the thalamus in a Hebbian-like manner. Moreover, long-term DBS also significantly changed the SC towards normality in terms of model-based measures of segregation and integration of information processing, two key concepts of brain organization. This novel approach using computational models to model the effects of Hebbian-like changes in SC allowed us to causally identify the possible underlying neural mechanisms of long-term DBS using rare case study data. In time, this could help predict the efficacy of individual DBS targeting and identify novel DBS targets.

Uncovering the underlying mechanisms and whole-brain dynamics of deep brain stimulation for Parkinson's disease.

Deep brain stimulation (DBS) for Parkinson’s disease is a highly effective treatment in controlling otherwise debilitating symptoms. Yet the underlying brain mechanisms are currently not well understood. Whole-brain computational modeling was used to disclose the effects of DBS during resting-state functional Magnetic Resonance Imaging in ten patients with Parkinson’s disease. Specifically, we explored the local and global impact that DBS has in creating asynchronous, stable or critical oscillatory conditions using a supercritical bifurcation model. We found that DBS shifts global brain dynamics of patients towards a Healthy regime. This effect was more pronounced in very specific brain areas such as the thalamus, globus pallidus and orbitofrontal regions of the right hemisphere (with the left hemisphere not analyzed given artifacts arising from the electrode lead). Global aspects of integration and synchronization were also rebalanced. Empirically, we found higher communicability and coherence brain measures during DBS-ON compared to DBS-OFF. Finally, using our model as a framework, artificial in silico DBS was applied to find potential alternative target areas for stimulation and whole-brain rebalancing. These results offer important insights into the underlying large-scale effects of DBS as well as in finding novel stimulation targets, which may offer a route to more efficacious treatments.

Brain fingerprints of olfaction: a novel structural method for assessing olfactory cortical networks in health and disease

Olfactory deficits are a common (often prodromal) symptom of neurodegenerative or psychiatric disorders. As such, olfaction could have great potential as an early biomarker of disease, for example using neuroimaging to investigate the breakdown of structural connectivity profile of the primary olfactory networks. We investigated the suitability for this purpose in two existing neuroimaging maps of olfactory networks. We found problems with both existing neuroimaging maps in terms of their structural connectivity to known secondary olfactory networks. Based on these findings, we were able to merge the existing maps to a new template map of olfactory networks with connections to all key secondary olfactory networks. We introduce a new method that combines diffusion tensor imaging with probabilistic tractography and pattern recognition techniques. This method can obtain comprehensive and reliable fingerprints of the structural connectivity underlying the neural processing of olfactory stimuli in normosmic adults. Combining the novel proposed method for structural fingerprinting with the template map of olfactory networks has great potential to be used for future neuroimaging investigations of olfactory function in disease. With time, the proposed method may even come to serve as structural biomarker for early detection of disease.

Pleasure of Food in the Brain

The survival of individuals as well as species relies on a few fundamental necessities. In order to survive, we need food, procreation and social interactions. These are arguably also the most pleasurable activities and they all are known to stimulate an array of sensory systems. The multisensory perception of food is very complex and includes more than just smell and taste. Flavour perception relies also on visual and auditory input. Food can be highly pleasurable and the act of eating extremely satisfying. The eating process can be described as a cyclic process of hunger, consumption and satiation. These three stages can also be described as the wanting, liking and learning phases, though learning does occur throughout the entire eating process, it is strongest in the later satiation phase. The related hedonic processing takes place in the orbitofrontal cortex (a crucial area for smell) where other multimodal stimuli are processed as well as reward and pleasure.

Neural Plasticity in Human Brain Connectivity: The Effects of Deep Brain Stimulation

Abstract Neural plasticity in adult humans is no longer believed to be impossible. The adult brain shows neuronal regeneration and plasticity in a number of domains. We know that certain disorders or accidents can change the brain in a malicious way. However, in more recent years we have come to learn that formation of new neurons also occurs in adults and that, for example, learning tasks can affect the structure of the brain and reorganize the brain network. The best example of this happens on the microscale with task repetition leading to strengthened neural connections. This mechanism is often referred to as Hebbian learning although other mechanisms could also be at play. Recent studies have shown that these changes in the brain can occur on a macroscale following deep brain stimulation (DBS). Following constant DBS (analogous to repetition in learning), some connections between the brain areas are strengthened resulting in long-term structural changes in the brain on the macroscale.Neural plasticity in adult humans is no longer believed to be impossible. The adult brain shows neuronal regeneration and plasticity in a number of domains. We know that certain disorders or accidents can change the brain in a malicious way. However, in more recent years we have come to learn that formation of new neurons also occurs in adults and that, for example, learning tasks can affect the structure of the brain and reorganize the brain network. The best example of this happens on the microscale with task repetition leading to strengthened neural connections. This mechanism is often referred to as Hebbian learning although other mechanisms could also be at play. Recent studies have shown that these changes in the brain can occur on a macroscale following deep brain stimulation (DBS). Following constant DBS (analogous to repetition in learning), some connections between the brain areas are strengthened resulting in long-term structural changes in the brain on the macroscale.

The Olfactory Cortex

The olfactory system is a unique and important sense which has, however, been underrepresented in research. It plays a crucial role in food selection and reproduction, ensuring survival for both the individual and the species. The olfactory system is unique compared to the other senses in that, among other things, information is not relayed via the thalamus, but instead projected directly to cortical regions such as the orbitofrontal cortex. This article describes the information processing in the olfactory system from the olfactory epithelium to the cortical projection areas, based on translational research and imaging studies, and details the multimodal interactions between olfaction and gustation. Equally, we describe the breakdown of the sense of smell that can be devastating and is implicated in anhedonia, the lack of pleasure, a key feature of mental illness.