| 1. |
- Awad, Amar, 1988-
(author)
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Functional brain imaging of sensorimotor dysfunction and restoration : investigations of discomplete spinal cord injury and deep brain stimulation for essential tremor
- 2022
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Doctoral thesis (other academic/artistic)abstract
- The nervous system exists to generate adaptive behaviour by processing sensory input from the body and the environment in order to produce appropriate motor output, and vice versa. Consequently, sensorimotor dysfunction is the basis of disability in most neurological pathologies. In the current thesis, I explore two conditions with different types and degrees of sensorimotor dysfunction by means of functional magnetic resonance imaging (fMRI). In part 1, I assess residual sensory connections to the brain in clinically complete spinal cord injury (SCI) with seemingly complete loss of sensorimotor function below the injury level. In part 2, fMRI is combined with deep brain stimulation (DBS) to investigate interventional mechanisms of restoring dysfunctional sensorimotor control in essential tremor (ET).Part 1: SCI disrupts the communication between the brain and below-injury body parts, but rarely results in complete anatomical transection of the spinal cord. In studies I and II, we demonstrate somatosensory cortex activation due to somatosensory (tactile and nociceptive) stimulation on below-level insensate body parts in clinically complete SCI. The results from studies I and II indicate preserved somatosensory conduction across the spinal lesion in some cases of clinically complete SCI, as classified according to international standards. This subgroup is referred to as sensory discomplete SCI, which represents a distinct injury phenotype with an intermediate degree of injury severity between clinically complete and incomplete SCI.Part 2: ET is effectively treated with DBS in the caudal zona incerta, but the neural mechanisms underlying the treatment effect are poorly understood. By exploring DBS mechanisms with fMRI, DBS was shown to cause modulation in the activity of the sensorimotor cerebello-cerebral regions during motor tasks (study III), but did not modulate the functional connectivity during resting-state (study IV).fMRI is a valuable tool to investigate sensorimotor dysfunction and restoration in SCI and DBS-treated ET. There is evidence for sensory discomplete SCI in about half of the patients with clinically complete SCI. DBS modulates DBS modulation of the activity in the sensorimotor cerebello-cerebral circuit during motor tasks, but not during resting-state, is action-dependent.
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| 2. |
- Awad, Amar, et al.
(author)
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Deep brain stimulation in the caudal zona incerta modulates the sensorimotor cerebello-cerebral circuit in essential tremor
- 2020
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In: NeuroImage. - : Elsevier. - 1053-8119 .- 1095-9572. ; 209
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Journal article (peer-reviewed)abstract
- Essential tremor is effectively treated with deep brain stimulation (DBS), but the neural mechanisms underlying the treatment effect are poorly understood. Essential tremor is driven by a dysfunctional cerebello-thalamo-cerebral circuit resulting in pathological tremor oscillations. DBS is hypothesised to interfere with these oscillations at the stimulated target level, but it is unknown whether the stimulation modulates the activity of the cerebello-thalamo-cerebral circuit during different task states (with and without tremor) in awake essential tremor patients. To address this issue, we used functional MRI in 16 essential tremor patients chronically implanted with DBS in the caudal zona incerta. During scanning, the patients performed unilateral tremor-inducing postural holding and pointing tasks as well as rest, with contralateral stimulation turned On and Off.We show that DBS exerts both task-dependent as well as task-independent modulation of the sensorimotor cerebello-cerebral regions (p ≤ 0.05, FWE cluster-corrected for multiple comparisons). Task-dependent modulation (DBS × task interaction) resulted in two patterns of stimulation effects. Firstly, activity decreases (blood oxygen level-dependent signal) during tremor-inducing postural holding in the primary sensorimotor cortex and cerebellar lobule VIII, and activity increases in the supplementary motor area and cerebellar lobule V during rest (p ≤ 0.05, post hoc two-tailed t-test). These effects represent differences at the effector level and may reflect DBS-induced tremor reduction since the primary sensorimotor cortex, cerebellum and supplementary motor area exhibit less motor task-activity as compared to the resting condition during On stimulation. Secondly, task-independent modulation (main effect of DBS) was observed as activity increase in the lateral premotor cortex during all motor tasks, and also during rest (p ≤ 0.05, post hoc two-tailed t-test). This task-independent effect may mediate the therapeutic effects of DBS through the facilitation of the premotor control over the sensorimotor circuit, making it less susceptible to tremor entrainment.Our findings support the notion that DBS in essential tremor is modulating the sensorimotor cerebello-cerebral circuit, distant to the stimulated target, and illustrate the complexity of stimulation mechanisms by demonstrating task-dependent as well as task-independent actions in cerebello-cerebral regions.
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| 3. |
- Karlsson, Fredrik, 1975-, et al.
(author)
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Control of phonatory onset and offset in Parkinson patients following deep brain stimulation of the subthalamic nucleus and caudal Zona Incerta
- 2012
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In: Parkinsonism & Related Disorders. - : Elsevier. - 1353-8020 .- 1873-5126. ; 18:7, s. 824-827
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Journal article (peer-reviewed)abstract
- Laryngeal hypokinesia is a common symptom in Parkinson’s disease (PD) that affects quality of life. Deep brain stimulation (DBS) is well recognized as a complementary method for treatment of motor symptoms in PD but the outcomes on patients’ control over phonatory alternation have yet not been clearly elucidated. The present study examined the effect of subthalamic nucleus STN-DBS (n=8, aged 51-72 yrs; median=63 yrs) and caudal Zona incerta cZi-DBS (n=8,aged 49-71 yrs; median=61 yrs) on control of onset and offset of phonation in connected speech. The patients were evaluated in a preoperatively (Med ON, 1.5 times the ordinary Levodopa dose) and 12 months postoperatively (Med ON, ordinary Levodopa dose). The results provided evidence of a progressive reduction in the ability to manifest alternations between voicing and voiceless states in a reading task. Mean proportion produced with inappropriate voicing increased from 47.6% to 55.3% and from 62.9% to 68.6% of the total duration for the two groups of patients between Pre-op and Post-op, Stim OFF evaluations. The medial and final parts of the fricative were more affected than the initial part, indicating an increased voicing lead into the following vowel. We propose that this reduction in phonatory control is be due to either progression of the disease, an effect of reduced Levodopa dosage or a microlesional effect. Patients’ proficiency in alternating between voiced and voiceless states in connected speech remained unaffected by both STN-DBS and cZi-DBS.
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| 4. |
- Karlsson, Fredrik, 1975-, et al.
(author)
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Pitch variability in patients with Parkinson’s disease : effects of deep brain stimulation of caudal zona incerta and subthalamic nucleus
- 2013
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In: Journal of Speech, Language and Hearing Research. - : American Speech-Language-Hearing Association. - 1092-4388 .- 1558-9102. ; 56:1, s. 150-158
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Journal article (peer-reviewed)abstract
- Objective The purpose of the present study was to examine the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) pitch characteristics of con- nected speech in patients with Parkinson’s disease (PD).Methods Sixteen patients were evaluated preoperatively and 12 months after DBS surgery. Eight pa- tients were implanted in the STN (aged 51-72 yrs; xC=63 yrs). Six received bilateral implanta- tion and two unilateral (left) implantation. Eight patients were bilaterally implanted in the cZi (aged 49-71 yrs; xC=60.8 yrs). Preoperative assessments were made after an L-Dopa challenge (approximately 1.5 times the ordinary dose). All postoperative examinations were made off and on stimulation, with a clinically optimized dose of L-dopa. Measurements of pitch range and var- iability were obtained from each utterance in a recorded read speech passage.Results Pitch range and coefficient of variation showed an increase in patients under STN-DBS. Patients under cZi-DBS showed no significant effects of treatment on investigated pitch properties.Conclusions STN-DBS was shown to increase pitch variation and range. The results provided no evidence of cZi-DBS having a beneficial effect on PD patients’ pitch variability.
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| 5. |
- Naesström, Matilda, et al.
(author)
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Distribution of electric field in patients with obsessive compulsive disorder treated with deep brain stimulation of the bed nucleus of stria terminalis
- 2022
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In: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 164, s. 193-202
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Journal article (peer-reviewed)abstract
- Background: Deep brain stimulation (DBS) is being investigated as a treatment for therapy-refractory obsessive-compulsive disorder (OCD). Many different brain targets are being trialled. Several of these targets such as the ventral striatum (including the nucleus accumbens (NAc)), the ventral capsule, the inferior thalamic peduncle and the bed nucleus of stria terminalis (BNST)) belong to the same network, are anatomically very close to one another, or even overlap. Data is still missing on how various stimulation parameters in a given target will affect surrounding anatomical areas and impact the clinical outcome of DBS.Methods: In a pilot study of eleven participants with DBS of the BNST, we investigate through patient-specific simulation of electric field, which anatomical areas are affected by the electric field, and if this can be related to the clinical results. Our study, combined individual patient’s stimulation parameters at 12 and 24-months follow-up with image data from the preoperative MRI and postoperative CT. These data were used to calculate the distribution of electric field and create individual anatomical models of the field of stimulation.Results: The individual electric stimulation fields by stimulation in the BNST were similar at both the 12 and 24-months follow up, involving mainly anterior limb of the internal capsule (ALIC), genu of the internal capsule (IC), BNST, fornix, anteromedial globus pallidus externa (GPe) and the anterior commissure. A statistical significant correlation (p < 0.05) between clinical effect measured by the Yale-Brown Obsessive Compulsive Scale and stimulation was found at the 12-month follow up in the ventral ALIC and anteromedial GPe.Conclusions: Many of the targets under investigation for OCD are in anatomical proximity. As seen in our study, off-target effects are overlapping. Therefore, DBS in the region of ALIC, NAc and BNST may perhaps be considered to be stimulation of the same target.
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| 6. |
- Sandström, Linda, et al.
(author)
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The effects of deep brain stimulation on speech intelligibility in persons with essential tremor
- 2020
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In: Journal of Speech, Language and Hearing Research. - : American Speech-Language-Hearing Association. - 1092-4388 .- 1558-9102. ; 63:2, s. 456-471
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Journal article (peer-reviewed)abstract
- Purpose: To investigate how deep brain stimulation (DBS) of the caudal zona incerta (cZi) affects speech intelligibility in persons with essential tremor (ET).Method: Thirty-five participants were evaluated: off stimulation, on chronic stimulation optimized to alleviate tremor, and during unilateral stimulation at increasing amplitude levels. At each stimulation condition, the participants read 10 unique nonsense sentences from the Swedish Test of Intelligibility. Two listeners, blinded to stimulation condition, transcribed all recorded sentences orthographically in a randomised procedure. A mean speech intelligibility score for each patient and stimulation condition was computed, and comparisons were made between scores off- and on stimulation.Results: Chronic cZi-DBS had no significant effect on speech intelligibility, and there was no difference in outcome between bilateral and unilateral treatments. During unilateral stimulation at increasing amplitudes, nine participants demonstrated deteriorating speech intelligibility. These nine participants were on average older and had more superior contacts activated during the evaluation compared with the participants without deterioration.Conclusions: Chronic cZi-DBS, optimized for tremor suppression, does not generally affect speech intelligibility in persons with ET. Furthermore, speech intelligibility may be preserved in many individuals, even when stimulated at high amplitudes. Adverse effects of high-amplitude unilateral stimulation observed in this study were associated with stimulation originating from a more superior location, as well as with the participants’ age. These results, highlighting age and stimulation location as contributing to speech intelligibility outcomes were, however, based on a limited number of individuals experiencing adverse effects with high-amplitude stimulation and should, therefore, be interpreted with caution.
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| 7. |
- Fytagoridis, Anders, et al.
(author)
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Deep Brain Stimulation of the Caudal Zona Incerta : Tremor Control in Relation to the Location of Stimulation Fields
- 2016
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In: Stereotactic and Functional Neurosurgery. - : S. Karger. - 1011-6125 .- 1423-0372. ; 94:6, s. 363-370
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Journal article (peer-reviewed)abstract
- Background: The caudal zona incerta (cZi) and posterior subthalamic area (PSA) are an emerging deep brain stimulation (DBS) target for essential tremor (ET). Objectives: To evaluate the efficacy of tremor control in relation to the anatomical locations of stimulation fields in 50 patients with ET and DBS of the cZi. Methods: A total of 240 contacts were evaluated separately with monopolar stimulation, and amplitudes were optimized for improvement of tremor and hand function. Stimulation fields, i.e., volumes of neural activation, were simulated for each optimized setting and assembled into probabilistic stimulation maps (PSMs). Results: There were differences in the anatomical distribution of PSMs associated with good versus poor tremor control. The location of PSMs which achieved good and excellent tremor control corresponded well with the PSM for the clinically used settings, and they were located within the superior part of the PSA. Conclusions: PSMs may serve as a useful tool for defining the most efficacious anatomical location of stimulation. The best tremor control in this series of cZi DBS was achieved with stimulation of the superior part of the PSA, which corresponds to the final part of the cerebellothalamic projections before they reach the ventral lateral thalamus.
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| 8. |
- Sundstedt, Stina, 1988-, et al.
(author)
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Swallowing function in Parkinson’s patients following Zona Incerta deep brain stimulation
- 2012
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In: Acta Neurologica Scandinavica. - : John Wiley & Sons. - 0001-6314 .- 1600-0404. ; 126:5, s. 350-356
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Journal article (peer-reviewed)abstract
- Objective The purpose of the present study was to examine if there was a negative effect of caudal Zona Incerta deep brain stimulation (cZI DBS) on pharyngeal swallowing function in Parkinson’s patients (PD). There are no former reports on swallowing and cZI DBS.Methods Eight patients (aged 49 to 71 years; median 62) were evaluated pre- and postoperatively, at six and 12 months after DBS surgery. Evaluation tools were Fiberoptic Endoscopic Evaluation of Swallowing examinations and patients’ self-assessments of the swallowing function including a visual analogue scale and quality of life related questions. The swallowing protocol included Rosenbeck’s Penetration-Aspiration Scale, Secretion Severity Scale and parameters for pre-swallow spillage, pharyngeal residue and pharyngeal clearance.Results There was no clear-cut effect of neurostimulation postoperatively at six and 12 months on any of the swallowing parameters except for pre-swallow spillage which was slightly worsened in the stimulation on condition 12m postoperatively. The answers to the self assessment questions did not vary significantly.Conclusions The effect of the stimulation on swallowing function varied among individuals but the overall outcome was that cZI DBS did not seem to have a negative influence on swallowing function in the eight patients studied.
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