| 1. |
- Nordmark, Per F., 1981-
(författare)
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Structural and functional changes in the brain after surgically repaired median nerve injury
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Despite the best available surgical repair, traumatic median nerve injury within the forearm typically causes lifelong impairment in hand function. This stems from an inadequate reinnervation of the nerves supporting sensory functions of the thumb, index and long finger, and of nerves supplying intrinsic hand muscles. This thesis examines whether median nerve injuries can cause structural and functional changes in the brain. Understanding such changes can help the development of new treatments for improved recovery of hand function.The first study introduces a novel apparatus and paradigm for examining tactile neural processing with fMRI under well-controlled behavioral conditions. The scientific issue challenged was whether, in healthy adults, different cortical areas could be involved in processing tactile stimuli depending on their temporal frequency content. In a threshold-tracking paradigm, the participants’ task was to detect oscillatory mechanical stimulations of various frequencies delivered to the tip of either left or right middle finger. Regardless of stimulated hand, tactile detection of audible frequencies (20 and 100 Hz) engaged the left auditory cortex while detection of slow object displacements (3 Hz) engaged visual cortex. These results corroborate and advance the metamodal theory of brain function, which posits that brain areas can contribute to sensory processing by performing specific computations – those for which they are specialized – regardless of input modality.The second and third studies concern structural and functional changes in the brain of adults with one reinnervated hand after an injury transecting the median nerve in the forearm. Healthy individuals matched for sex, handedness and age served as controls. Irrespective of side of injury (left or right), voxel-based morphometry applied on T1 MR-images revealed reductions of gray matter in the left ventral and right dorsal premotor cortex, and reductions of white matter in related commissural pathways. We interpreted these as activity-dependent structural adaptations to reduced neural processing linked to restrictions in the diversity of the natural manual dexterity repertoire caused by a disturbed innervation of the hand. Conversely, increases in gray matter were observed bilaterally in a motion-processing visual cortical area. We interpreted this as a structural manifestation of increased neural processing linked to greater dependence on vision for controlling manual dexterity due to impaired tactile innervation of the affected hand.To reveal functional changes in tactile cortical processing after median nerve reinnervation, we recorded brain activity using fMRI when study participants performed perceptually demanding tactile threshold-tracking and oddball detection tasks with our novel apparatus. The hand representation of the contralesional primary somatosensory cortex (S1) showed greater activity compared to the controls when the reinnervated index finger was engaged in the tasks, but strikingly also when fingers of both hands innervated by uninjured nerves were engaged, i.e., little finger of the reinnervated hand and index and little finger of the other hand. The generally increased activity indicates a general disinhibition of contralateral S1, suggesting that increased functional reorganization is an ongoing process of chronic nerve injury. In addition, prefrontal areas implicated in processes that support decision-making and response selection showed increased activity, suggesting that such processes were more computationally demanding after nerve injury.Together, these results indicate that brain areas can undergo significant changes after peripheral nerve injury, even when followed by best available surgical repair and reinnervation conditions. These changes can include activity-dependent structural adaptations consisting of either regional decreases or increases in gray matter concentration, which likely depend on an area's functional specialization and on changes in its processing load due to behavioral constraints imposed by the injury. Moreover, the results also suggest that the affected hand's primary cortical projection area is still in a state of ongoing functional reorganization despite the fact that peripheral reinnervation of the hand should have been completed long ago, which should inspire the development of new therapeutic regimens for what today is considered a chronic impairment.
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| 2. |
- Galván, Ignacio Fdez., et al.
(författare)
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OpenMolcas : From Source Code to Insight
- 2019
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Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 15:11, s. 5925-5964
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Tidskriftsartikel (refereegranskat)abstract
- In this Article we describe the OpenMolcas environment and invite the computational chemistry community to collaborate. The open-source project already includes a large number of new developments realized during the transition from the commercial MOLCAS product to the open-source platform. The paper initially describes the technical details of the new software development platform. This is followed by brief presentations of many new methods, implementations, and features of the OpenMolcas program suite. These developments include novel wave function methods such as stochastic complete active space self-consistent field, density matrix renormalization group (DMRG) methods, and hybrid multiconfigurational wave function and density functional theory models. Some of these implementations include an array of additional options and functionalities. The paper proceeds and describes developments related to explorations of potential energy surfaces. Here we present methods for the optimization of conical intersections, the simulation of adiabatic and nonadiabatic molecular dynamics, and interfaces to tools for semiclassical and quantum mechanical nuclear dynamics. Furthermore, the Article describes features unique to simulations of spectroscopic and magnetic phenomena such as the exact semiclassical description of the interaction between light and matter, various X-ray processes, magnetic circular dichroism, and properties. Finally, the paper describes a number of built-in and add-on features to support the OpenMolcas platform with postcalculation analysis and visualization, a multiscale simulation option using frozen-density embedding theory, and new electronic and muonic basis sets.
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| 3. |
- Häger Ross, Charlotte, 1962-
(författare)
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To grip and not to slip : sensorimotor mechanisms in reactive control of grasp stability
- 1995
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The reactive control of fingertip forces maintaining grasp stability was examined in man during a prehensile task. Blindfolded subjects used the precision grip between the tips of index finger and thumb to restrain an object that was subjected to unpredictable load forces. These were delivered tangential to the parallel grip surfaces of the object. Load forces, grip forces (perpendicular to the grip surfaces) and position of the object were recorded.Subjects automatically adjusted the grip forces to loads of various amplitudes and rates. Thereby they maintained a reliable safety margin against frictional slips without using excessive grip forces. A rapid rise in grip force lasting about 0.2 s was triggered after a short delay following the onset of a sustained ramp load increase. This 'catch-up' response caused a quick restoration of an adequate grip:load force ratio that prevented frictional slips. If the ramp load continued to increase after the catchup response, the grip force also increased in parallel with the load change in a 'tracking' manner. Consequently, during the hold phases of 'ramp-and-hold' loads, the employed grip forces were approximately proportional to the load amplitude. Sensory information about the rate of change of the load force parametrically scaled the 'catchup' and 'tracking' responses.Following anesthetic block of sensory input from the digits, the grip responses were both delayed and attenuated or even abolished. To compensate for these impairments, subjects had to voluntarily maintain exceedingly high grip forces to prevent the object from slipping. The grip control improved slightly during hand and forearm support conditions that allowed marked wrist movements to occur in response to the loading. This indicates that signals from receptors in muscles, joints or skin areas proximal to the digits can to some extent be used to adjust grip forces during impaired digital sensibility. In contrast, these signals had only minor influence on the control during normal digital sensibility.Grip responses to loads delivered in various directions revealed that the load direction, in relation to gravity and to the hand's geometry, represents intrinsic task variables in the automatic processes that maintain a stable grasp. The load direction influenced both the response latencies and the magnitudes of the grip responses. The response latencies were shortest for loads in directions that were the most critical with regard to the consequences of frictional slippage, i.e., loads directed away from the palm or in the direction of gravity. Recordings of signals in cutaneous afferents innervating the finger tips demonstrated that these effects on the response latencies depended on differences in the time needed by the central nervous system to implement the motor responses. The short latencies in the most ‘criticar load directions may reflect the preparation of a default response, while additional central processing would be needed to execute the response to loads in other directions. Adjustments to local frictional anisotropies at the digit-object interface largely explained the magnitude effects.In conclusion, grip responses are automatically adjusted to the current loading condition during unpredictable loading of a hand held object. Subjects call up a previously acquired sensorimotor transform that supports grasp stability by preventing both object slippage and excessive grip forces. Cutaneous sensory information about tangential forces and frictional conditions at the digit-object interface is used to initiate and scale the grip responses to the current loading conditions, largely in a predictive manner.
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