Tractography Study of Deep Brain Stimulation of the Anterior Cingulate Cortex in Chronic Pain: Key to Improve the Targeting.

BACKGROUND: Deep brain stimulation (DBS) of the anterior cingulate cortex (ACC) is a new treatment for alleviating intractable neuropathic pain. However, it fails to help some patients. The large size of the ACC and the intersubject variability make it difficult to determine the optimal site to position DBS electrodes. The aim of this work was therefore to compare the ACC connectivity of patients with successful versus unsuccessful DBS outcomes to help guide future electrode placement. METHODS: Diffusion magnetic resonance imaging (dMRI) and probabilistic tractography were performed preoperatively in 8 chronic pain patients (age 53.4 ± 6.1 years, 2 females) with ACC DBS, of whom 6 had successful (SO) and 2 unsuccessful outcomes (UOs) during a period of trialing. RESULTS: The number of patients was too small to demonstrate any statistically significant differences. Nevertheless, we observed differences between patients with successful and unsuccessful outcomes in the fiber tract projections emanating from the volume of activated tissue around the electrodes. A strong connectivity to the precuneus area seems to predict unsuccessful outcomes in our patients (UO: 160n/SO: 27n), with (n), the number of streamlines per nonzero voxel. On the other hand, connectivity to the thalamus and brainstem through the medial forebrain bundle (MFB) was only observed in SO patients. CONCLUSIONS: These findings could help improve presurgical planning by optimizing electrode placement, to selectively target the tracts that help to relieve patients' pain and to avoid those leading to unwanted effects.

Thalamo-Cortical Disruption Contributes to Short-Term Memory Deficits in Patients with Medial Temporal Lobe Damage.

Short-term (STM) and long-term memory (LTM) have largely been considered as separate brain systems reflecting fronto-parietal and medial temporal lobe (MTL) functions, respectively. This functional dichotomy has been called into question by evidence of deficits on aspects of working memory in patients with MTL damage, suggesting a potentially direct hippocampal contribution to STM. As the hippocampus has direct anatomical connections with the thalamus, we tested the hypothesis that damage to thalamic nuclei regulating cortico-cortical interactions may contribute to STM deficits in patients with hippocampal dysfunction. We used diffusion-weighted magnetic resonance imaging-based tractography to identify anatomical subdivisions in patients with MTL epilepsy. From these, we measured resting-state functional connectivity with detailed cortical divisions of the frontal, temporal, and parietal lobes. Whereas thalamo-temporal functional connectivity reflected LTM performance, thalamo-prefrontal functional connectivity specifically predicted STM performance. Notably, patients with hippocampal volume loss showed thalamic volume loss, most prominent in the pulvinar region, not detected in patients with normal hippocampal volumes. Aberrant thalamo-cortical connectivity in the epileptic hemisphere was mirrored in a loss of behavioral association with STM performance specifically in patients with hippocampal atrophy. These findings identify thalamo-cortical disruption as a potential mechanism contributing to STM deficits in the context of MTL damage.

Slow-wave activity saturation and thalamocortical isolation during propofol anesthesia in humans.

The altered state of consciousness produced by general anesthetics is associated with a variety of changes in the brain's electrical activity. Under hyperpolarizing influences such as anesthetic drugs, cortical neurons oscillate at ~1 Hz, which is measurable as slow waves in the electroencephalogram (EEG). We have administered propofol anesthesia to 16 subjects and found that, after they had lost behavioral responsiveness (response to standard sensory stimuli), each individual's EEG slow-wave activity (SWA) rose to saturation and then remained constant despite increasing drug concentrations. We then simultaneously collected functional magnetic resonance imaging and EEG data in 12 of these subjects during propofol administration and sensory stimulation. During the transition to SWA saturation, the thalamocortical system became isolated from sensory stimuli, whereas internal thalamocortical exchange persisted. Rather, an alternative and more fundamental cortical network (which includes the precuneus) responded to all sensory stimulation. We conclude that SWA saturation is a potential individualized indicator of perception loss that could prove useful for monitoring depth of anesthesia and studying altered states of consciousness.

Human and monkey ventral prefrontal fibers use the same organizational principles to reach their targets: tracing versus tractography.

This article is a comparative study of white matter projections from ventral prefrontal cortex (vPFC) between human and macaque brains. We test whether the organizational rules that vPFC connections follow in macaques are preserved in humans. These rules concern the trajectories of some of the white matter projections from vPFC and how the position of regions in the vPFC dictate the trajectories of their projections in the white matter. To address this question, we present a novel approach that combines direct tracer measurements of entire white matter trajectories in macaque monkeys with diffusion MRI tractography of both macaques and humans. The approach allows us to provide explicit validation of diffusion tractography and transfer tractography strategies across species to test the extent to which inferences from macaques can be applied to human neuroanatomy. Apart from one exception, we found a remarkable overlap between the two techniques in the macaque. Furthermore, the organizational principles followed by vPFC tracts in macaques are preserved in humans.

Cortical and subcortical connectivity changes during decreasing levels of consciousness in humans: a functional magnetic resonance imaging study using propofol.

While ubiquitous, pharmacological manipulation of consciousness remains poorly defined and incompletely understood (Prys-Roberts, 1987). This retards anesthetic drug development, confounds interpretation of animal studies conducted under anesthesia, and limits the sensitivity of clinical monitors of cerebral function to intact perception. Animal and human studies propose a functional "switch" at the level of the thalamus, with inhibition of thalamo-cortical transmission characterizing loss of consciousness (Alkire et al., 2000; Mashour, 2006). We investigated the effects of propofol, widely used for anesthesia and sedation, on spontaneous and evoked cerebral activity using functional magnetic resonance imaging (fMRI). A series of auditory and noxious stimuli was presented to eight healthy volunteers at three behavioral states: awake, "sedated" and "unresponsive." Performance in a verbal task and the absence of a response to verbal stimulation, rather than propofol concentrations, were used to define these states clinically. Analysis of stimulus-related blood oxygenation level-dependent signal changes identified reductions in cortical and subcortical responses to auditory and noxious stimuli in sedated and unresponsive states. A specific reduction in activity within the putamen was noted and further investigated with functional connectivity analysis. Progressive failure to perceive or respond to auditory or noxious stimuli was associated with a reduction in the functional connectivity between the putamen and other brain regions, while thalamo-cortical connectivity was relatively preserved. This result has not been previously described and suggests that disruption of subcortical thalamo-regulatory systems may occur before, or even precipitate, failure of thalamo-cortical transmission with the induction of unconsciousness.

Determination of the human brainstem respiratory control network and its cortical connections in vivo using functional and structural imaging.

This study combined functional and structural magnetic resonance imaging techniques, optimized for the human brainstem, to investigate activity in brainstem respiratory control centres in a group of 12 healthy human volunteers. We stimulated respiration with carbon dioxide (CO(2)), and utilized novel methodology to separate its vascular from its neuronal effects upon the blood oxygen level dependent (BOLD) signal. In the brainstem we observed activity in the dorsal rostral pons (representing the Kölliker-Fuse/parabrachial (KF/PB) nuclei and locus coeruleus), the inferior ventral pons and the dorsal and lateral medulla. These areas of activation correspond to respiratory nuclei identified in recent rodent studies. Our results also reveal functional participation of the anteroventral (AV), ventral posterolateral (VPL) ventrolateral thalamic nuclei, and the posterior putamen in the response to CO(2) stimulation, suggesting that these centres may play a role in gating respiratory information to the cortex. As the functional imaging plane was limited to the brainstem and adjacent subcortical areas, we employed diffusion tractography to further investigate cortical connectivity of the thalamic activations. This revealed distinct connectivity profiles of these thalamic activations suggesting subdivision of the thalamus with regards to respiratory control. From these results we speculate that the thalamus plays an important role in integrating respiratory signals to and from the brainstem respiratory centres.