Disparate connectivity for structural and functional networks is revealed when physical location of the connected nodes is considered

Macroscopic brain networks have been widely described with the manifold of metrics available using graph theory. However, most analyses do not incorporate information about the physical position of network nodes. Here, we provide a multimodal macroscopic network characterization while considering the physical positions of nodes. To do so, we examined anatomical and functional macroscopic brain networks in a sample of twenty healthy subjects. Anatomical networks are obtained with a graph based tractography algorithm from diffusion-weighted magnetic resonance images (DW-MRI). Anatomical con- nections identified via DW-MRI provided probabilistic constraints for determining the connectedness of 90 dif- ferent brain areas. Functional networks are derived from temporal linear correlations between blood-oxygenation level-dependent signals derived from the same brain areas. Rentian Scaling analysis, a technique adapted from very- large-scale integration circuits analyses, shows that func- tional networks are more random and less optimized than the anatomical networks. We also provide a new metric that allows quantifying the global connectivity arrange- ments for both structural and functional networks. While the functional networks show a higher contribution of inter-hemispheric connections, the anatomical networks highest connections are identified in a dorsal?ventral arrangement. These results indicate that anatomical and functional networks present different connectivity organi- zations that can only be identified when the physical locations of the nodes are included in the analysis.

Towards Closed-loop Deep Brain Stimulation: Behavior Recognition from Human STN

Deep brain stimulation (DBS) provides significant therapeutic benefit for movement disorders such as Parkinson’s disease (PD). Current DBS devices lack real-time feedback (thus are open loop) and stimulation parameters are adjusted during scheduled visits with a clinician. A closed-loop DBS system may reduce power consumption and side effects by adjusting stimulation parameters based on patient’s behavior. Thus behavior detection is a major step in designing such systems. Various physiological signals can be used to recognize the behaviors. Subthalamic Nucleus (STN) Local field Potential (LFP) is a great candidate signal for the neural feedback, because it can be recorded from the stimulation lead and does not require additional sensors. This thesis proposes novel detection and classification techniques for behavior recognition based on deep brain LFP. Behavior detection from such signals is the vital step in developing the next generation of closed-loop DBS devices. LFP recordings from 13 subjects are utilized in this study to design and evaluate our method. Recordings were performed during the surgery and the subjects were asked to perform various behavioral tasks. Various techniques are used understand how the behaviors modulate the STN. One method studies the time-frequency patterns in the STN LFP during the tasks. Another method measures the temporal inter-hemispheric connectivity of the STN as well as the connectivity between STN and Pre-frontal Cortex (PFC). Experimental results demonstrate that different behaviors create different m odulation patterns in STN and it’s connectivity. We use these patterns as features to classify behaviors. A method for single trial recognition of the patient’s current task is proposed. This method uses wavelet coefficients as features and support vector machine (SVM) as the classifier for recognition of a selection of behaviors: speech, motor, and random. The proposed method is 82.4% accurate for the binary classification and 73.2% for classifying three tasks. As the next step, a practical behavior detection method which asynchronously detects behaviors is proposed. This method does not use any priori knowledge of behavior onsets and is capable of asynchronously detect the finger movements of PD patients. Our study indicates that there is a motor-modulated inter-hemispheric connectivity between LFP signals recorded bilaterally from STN. We utilize a non-linear regression method to measure this inter-hemispheric connectivity and to detect the finger movements. Our experimental results using STN LFP recorded from eight patients with PD demonstrate this is a promising approach for behavior detection and developing novel closed-loop DBS systems.

Benthic and planktic foraminiferal stable isotope record and coccolith abundance spanning the last 500,000 years of ODP Hole 121-758C

The Indian Summer Monsoon (ISM) is an inter-hemispheric and highly variable ocean-atmosphere-land interaction that directly affects the densely populated Indian subcontinent. Here, we present new records of palaeoceanographic variability that span the last 500,000 years from the eastern equatorial Indian Ocean, a relatively under-sampled area of ISM influence. We have generated carbon and oxygen stable isotope records from three foraminiferal species from Ocean Drilling Program Site 758 (5°N, 90°E) to investigate the oceanographic history of this region. We interpret our resultant Dd18O (surface-thermocline) record of upper water-column stratification in the context of past ISM variability, and compare orbital phase relationships in our Site 758 data to other climate and monsoon proxies in the region. Results suggest that upper water-column stratification at Site 758, which is dominated by variance at precession and half-precession frequencies (23, 19 and 11 ka), is forced by both local (5°N) insolation and ISM winds. In the precession (23 ka) band, stratification minima at Site 758 lag northern hemisphere summer insolation maxima (precession minima) by 9 ka, which is consistent with Arabian Sea ISM phase estimates and suggests a common wind forcing in both regions. This phase implicates a strong sensitivity to both ice volume and southern hemisphere insolation forcing via latent heat export from the southern subtropical Indian Ocean. Additionally, we find evidence of possible overprinting of millennial-scale events during glacial terminations in our stratification record, which suggests an influence of remote abrupt climate events on ISM dynamics.

Tropical climate and vegetation simulations during the Heinrich event 1 using an Earth System Model of Intermediate Complexity (EMIC) - the University of Victoria Earth System-Climate Model (UVic ESCM)

Abrupt climate changes from 18 to 15 thousand years before present (kyr BP) associated with Heinrich Event 1 (HE1) had a strong impact on vegetation patterns not only at high latitudes of the Northern Hemisphere, but also in the tropical regions around the Atlantic Ocean. To gain a better understanding of the linkage between high and low latitudes, we used the University of Victoria (UVic) Earth System-Climate Model (ESCM) with dynamical vegetation and land surface components to simulate four scenarios of climate-vegetation interaction: the pre-industrial era, the Last Glacial Maximum (LGM), and a Heinrich-like event with two different climate backgrounds (interglacial and glacial). We calculated mega-biomes from the plant-functional types (PFTs) generated by the model to allow for a direct comparison between model results and palynological vegetation reconstructions. Our calculated mega-biomes for the pre-industrial period and the LGM corresponded well with biome reconstructions of the modern and LGM time slices, respectively, except that our pre-industrial simulation predicted the dominance of grassland in southern Europe and our LGM simulation resulted in more forest cover in tropical and sub-tropical South America. The HE1-like simulation with a glacial climate background produced sea-surface temperature patterns and enhanced inter-hemispheric thermal gradients in accordance with the "bipolar seesaw" hypothesis. We found that the cooling of the Northern Hemisphere caused a southward shift of those PFTs that are indicative of an increased desertification and a retreat of broadleaf forests in West Africa and northern South America. The mega-biomes from our HE1 simulation agreed well with paleovegetation data from tropical Africa and northern South America. Thus, according to our model-data comparison, the reconstructed vegetation changes for the tropical regions around the Atlantic Ocean were physically consistent with the remote effects of a Heinrich event under a glacial climate background.

Stable carbon isotopes of Planulina wuellerstorfi of sediment core MD01-2444

The observation that Greenland and Antarctic temperatures have followed a specific 'asymmetrical' pattern on millennial time-scales sets rigid constraints on any viable theory of abrupt climate change. The further observation that the very same asymmetry is also reflected in planktonic and benthic d18O measurements from the Northeast Atlantic has extended this constraint to include a specific response in the ocean. Here we present records of deep-water temperature, d18O and d13C variability from the Northeast Atlantic that help to shed light on the links between overturning circulation perturbations, sea-level variability and inter-hemispheric climate change on millennial time-scales. Results indicate that while deep-water temperatures in the Northeast Atlantic have tracked Greenland climate, the d18O signature of local deepwater (d18Odw) has varied in a manner more reminiscent of Antarctic temperature variability. The previously identified correspondence of Antarctic warm events with benthic d18O minima in the Northeast Atlantic is thus found to apply specifically to d18Odw minima, and to extend beyond Marine Isotope Stage 3 to the entirety of the last 50 ka. It is impossible to reconcile completely the Iberian Margin d18Odw record with existing reconstructions of millennial sea-level variability, leading to the conclusion that a significant portion of the d18Odw record must represent local hydrographic change. This is supported by benthic d13C measurements, which suggest the incursion during Greenland stadials of a colder, low-d18O and low-d13C water-mass, of presumed Antarctic origin. These observations confirm a one-to-one coupling of inter-hemispheric climate events with changes in the Atlantic overturning circulation, but fail to rule in or out a unique mechanism by which they were triggered.

Radiocarbon variations from the southern hemisphere, 10,350-9700 cal BP

We have made AMS measurements on a series of 10-ring samples from a subfossil Huon pine log found in western Tasmania (42degreesS, 145degreesE). The results show a pronounced rise in Delta(14)C over the first 200 years, and a decrease over the following 160 years. Tree-ring width measurements indicate that this log (catalogue SRT-447) can be cross-dated with another subfossil log (SRT-416) for which a series of high-precision radiometric C-14 measurements have previously been made. When the two tree-ring series are thus aligned, SRT-447 is the older of the two logs, and there is a 139-year overlap. We then have a Huon pine floating chronology spanning 680 years, with C-14 measurements attached. The C-14 data sets agree well within the period of overlap indicated by the tree-rings. The C-14 variations from Huon pine show excellent agreement with those from German oak and pine for the period 10,350-9670 cal BP. Aligning the Huon pine C-14 Series with that from German oak and pine allows us to examine the inter-hemispheric offset in C-14 dates in the early Holocene. (C) 2004 Elsevier B.V. All rights reserved.

Left-right information flow in the brain during EEG arousals

In disorders such as sleep apnea, sleep is fragmented with frequent EEG-arousal (EEGA) as determined via changes in the sleep-electroencephalogram. EEGA is a poorly understood, complicated phenomenon which is critically important in studying the mysteries of sleep. In this paper we study the information flow between the left and right hemispheres of the brain during the EEGA as manifested through inter-hemispheric asynchrony (IHA) of the surface EEG. EEG data (using electrodes A1/C4 and A2/C3 of international 10-20 system) was collected from 5 subjects undergoing routine polysomnography (PSG). Spectral correlation coefficient (R) was computed between EEG data from two hemispheres for delta-delta(0.5-4 Hz), theta-thetas(4.1-8 Hz), alpha-alpha(8.1-12 Hz) & beta-beta(12.1-25 Hz) frequency bands, during EEGA events. EEGA were graded in 3 levels as (i) micro arousals (3-6 s), (ii) short arousals (6.1-10 s), & (iii) long arousals (10.1-15 s). Our results revealed that in beta band, IHA increases above the baseline after the onset of EEGA and returns to the baseline after the conclusion of event. Results indicated that the duration of EEGA events has a direct influence on the onset of IHA. The latency (L) between the onset of arousals and IHA were found to be L=2plusmn0.5 s (for micro arousals), 4plusmn2.2 s (short arousals) and 6.5plusmn3.6 s (long arousals)

A novel method for studying the cortical processing of human swallowing using Synthetic Aperture Magnetometry(SAM)

Background/Aims: Positron emission tomography has been applied to study cortical activation during human swallowing, but employs radio-isotopes precluding repeated experiments and has to be performed supine, making the task of swallowing difficult. Here we now describe Synthetic Aperture Magnetometry (SAM) as a novel method of localising and imaging the brain's neuronal activity from magnetoencephalographic (MEG) signals to study the cortical processing of human volitional swallowing in the more physiological prone position. Methods: In 3 healthy male volunteers (age 28–36), 151-channel whole cortex MEG (Omega-151, CTF Systems Inc.) was recorded whilst seated during the conditions of repeated volitional wet swallowing (5mls boluses at 0.2Hz) or rest. SAM analysis was then performed using varying spatial filters (5–60Hz) before co-registration with individual MRI brain images. Activation areas were then identified using standard sterotactic space neuro-anatomical maps. In one subject repeat studies were performed to confirm the initial study findings. Results: In all subjects, cortical activation maps for swallowing could be generated using SAM, the strongest activations being seen with 10–20Hz filter settings. The main cortical activations associated with swallowing were in: sensorimotor cortex (BA 3,4), insular cortex and lateral premotor cortex (BA 6,8). Of relevance, each cortical region displayed consistent inter-hemispheric asymmetry, to one or other hemisphere, this being different for each region and for each subject. Intra-subject comparisons of activation localisation and asymmetry showed impressive reproducibility. Conclusion: SAM analysis using MEG is an accurate, repeatable, and reproducible method for studying the brain processing of human swallowing in a more physiological manner and provides novel opportunities for future studies of the brain-gut axis in health and disease.

Mobility changes in older age: neuropsychological, neurophysiological and cognitive predictors of successful adaptation in a real world scenario

The aims of this thesis were to investigate the neuropsychological, neurophysiological, and cognitive contributors to mobility changes with increasing age. In a series of studies with adults aged 45-88 years, unsafe pedestrian behaviour and falls were investigated in relation to i) cognitive functions (including response time variability, executive function, and visual attention tests), ii) mobility assessments (including gait and balance and using motion capture cameras), iii) motor initiation and pedestrian road crossing behavior (using a simulated pedestrian road scene), iv) neuronal and functional brain changes (using a computer based crossing task with magnetoencephalography), and v) quality of life questionnaires (including fear of falling and restricted range of travel). Older adults are more likely to be fatally injured at the far-side of the road compared to the near-side of the road, however, the underlying mobility and cognitive processes related to lane-specific (i.e. near-side or far-side) pedestrian crossing errors in older adults is currently unknown. The first study explored cognitive, motor initiation, and mobility predictors of unsafe pedestrian crossing behaviours. The purpose of the first study (Chapter 2) was to determine whether collisions at the near-side and far-side would be differentially predicted by mobility indices (such as walking speed and postural sway), motor initiation, and cognitive function (including spatial planning, visual attention, and within participant variability) with increasing age. The results suggest that near-side unsafe pedestrian crossing errors are related to processing speed, whereas far-side errors are related to spatial planning difficulties. Both near-side and far-side crossing errors were related to walking speed and motor initiation measures (specifically motor initiation variability). The salient mobility predictors of unsafe pedestrian crossings determined in the above study were examined in Chapter 3 in conjunction with the presence of a history of falls. The purpose of this study was to determine the extent to which walking speed (indicated as a salient predictor of unsafe crossings and start-up delay in Chapter 2), and previous falls can be predicted and explained by age-related changes in mobility and cognitive function changes (specifically within participant variability and spatial ability). 53.2% of walking speed variance was found to be predicted by self-rated mobility score, sit-to-stand time, motor initiation, and within participant variability. Although a significant model was not found to predict fall history variance, postural sway and attentional set shifting ability was found to be strongly related to the occurrence of falls within the last year. Next in Chapter 4, unsafe pedestrian crossing behaviour and pedestrian predictors (both mobility and cognitive measures) from Chapter 2 were explored in terms of increasing hemispheric laterality of attentional functions and inter-hemispheric oscillatory beta power changes associated with increasing age. Elevated beta (15-35 Hz) power in the motor cortex prior to movement, and reduced beta power post-movement has been linked to age-related changes in mobility. In addition, increasing recruitment of both hemispheres has been shown to occur and be beneficial to perform similarly to younger adults in cognitive tasks (Cabeza, Anderson, Locantore, & McIntosh, 2002). It has been hypothesised that changes in hemispheric neural beta power may explain the presence of more pedestrian errors at the farside of the road in older adults. The purpose of the study was to determine whether changes in age-related cortical oscillatory beta power and hemispheric laterality are linked to unsafe pedestrian behaviour in older adults. Results indicated that pedestrian errors at the near-side are linked to hemispheric bilateralisation, and neural overcompensation post-movement, 4 whereas far-side unsafe errors are linked to not employing neural compensation methods (hemispheric bilateralisation). Finally, in Chapter 5, fear of falling, life space mobility, and quality of life in old age were examined to determine their relationships with cognition, mobility (including fall history and pedestrian behaviour), and motor initiation. In addition to death and injury, mobility decline (such as pedestrian errors in Chapter 2, and falls in Chapter 3) and cognition can negatively affect quality of life and result in activity avoidance. Further, number of falls in Chapter 3 was not significantly linked to mobility and cognition alone, and may be further explained by a fear of falling. The objective of the above study (Study 2, Chapter 3) was to determine the role of mobility and cognition on fear of falling and life space mobility, and the impact on quality of life measures. Results indicated that missing safe pedestrian crossing gaps (potentially indicating crossing anxiety) and mobility decline were consistent predictors of fear of falling, reduced life space mobility, and quality of life variance. Social community (total number of close family and friends) was also linked to life space mobility and quality of life. Lower cognitive functions (particularly processing speed and reaction time) were found to predict variance in fear of falling and quality of life in old age. Overall, the findings indicated that mobility decline (particularly walking speed or walking difficulty), processing speed, and intra-individual variability in attention (including motor initiation variability) are salient predictors of participant safety (mainly pedestrian crossing errors) and wellbeing with increasing age. More research is required to produce a significant model to explain the number of falls.

The influence of interhemispheric connections on ongoing and evoked orientation preference maps and spiking activity in the cat primary visual cortex

In the primary visual cortex, neurons with similar physiological features are clustered together in columns extending through all six cortical layers. These columns form modular orientation preference maps. Long-range lateral fibers are associated to the structure of orientation maps since they do not connect columns randomly; they rather cluster in regular intervals and interconnect predominantly columns of neurons responding to similar stimulus features. Single orientation preference maps – the joint activation of domains preferring the same orientation - were observed to emerge spontaneously and it was speculated whether this structured ongoing activation could be caused by the underlying patchy lateral connectivity. Since long-range lateral connections share many features, i.e. clustering, orientation selectivity, with visual inter-hemispheric connections (VIC) through the corpus callosum we used the latter as a model for long-range lateral connectivity. In order to address the question of how the lateral connectivity contributes to spontaneously generated maps of one hemisphere we investigated how these maps react to the deactivation of VICs originating from the contralateral hemisphere. To this end, we performed experiments in eight adult cats. We recorded voltage-sensitive dye (VSD) imaging and electrophysiological spiking activity in one brain hemisphere while reversible deactivating the other hemisphere with a cooling technique. In order to compare ongoing activity with evoked activity patterns we first presented oriented gratings as visual stimuli. Gratings had 8 different orientations distributed equally between 0º and 180º. VSD imaged frames obtained during ongoing activity conditions were then compared to the averaged evoked single orientation maps in three different states: baseline, cooling and recovery. Kohonen self-organizing maps were also used as a means of analysis without prior assumption (like the averaged single condition maps) on ongoing activity. We also evaluated if cooling had a differential effect on evoked and ongoing spiking activity of single units. We found that deactivating VICs caused no spatial disruption on the structure of either evoked or ongoing activity maps. The frequency with which a cardinally preferring (0º or 90º) map would emerge, however, decreased significantly for ongoing but not for evoked activity. The same result was found by training self-organizing maps with recorded data as input. Spiking activity of cardinally preferring units also decreased significantly for ongoing when compared to evoked activity. Based on our results we came to the following conclusions: 1) VICs are not a determinant factor of ongoing map structure. Maps continued to be spontaneously generated with the same quality, probably by a combination of ongoing activity from local recurrent connections, thalamocortical loop and feedback connections. 2) VICs account for a cardinal bias in the temporal sequence of ongoing activity patterns, i.e. deactivating VIC decreases the probability of cardinal maps to emerge spontaneously. 3) Inter- and intrahemispheric long-range connections might serve as a grid preparing primary visual cortex for likely junctions in a larger visual environment encompassing the two hemifields.