Cognitive processing slows with age. We sought to determine the importance of white matter integrity, assessed by diffusion tensor imaging (DTI), at influencing cognitive processing speed among ...normal older adults, assessed using a novel battery of computerized, non-verbal, choice reaction time tasks. We studied 131 cognitively normal adults aged 55-87 using a cross-sectional design. Each participant underwent our test battery, as well as MRI with DTI. We carried out cross-subject comparisons using tract-based spatial statistics. As expected, reaction time slowed significantly with age. In diffuse areas of frontal and parietal white matter, especially the anterior corpus callosum, fractional anisotropy values correlated negatively with reaction time. The genu and body of the corpus callosum, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus were among the areas most involved. This relationship was not explained by gray or white matter atrophy or by white matter lesion volume. In a statistical mediation analysis, loss of white matter integrity mediated the relationship between age and cognitive processing speed.
Neural recordings using invasive devices in humans can elucidate the circuits underlying brain disorders, but have so far been limited to short recordings from externalized brain leads in a hospital ...setting or from implanted sensing devices that provide only intermittent, brief streaming of time series data. Here, we report the use of an implantable two-way neural interface for wireless, multichannel streaming of field potentials in five individuals with Parkinson's disease (PD) for up to 15 months after implantation. Bilateral four-channel motor cortex and basal ganglia field potentials streamed at home for over 2,600 h were paired with behavioral data from wearable monitors for the neural decoding of states of inadequate or excessive movement. We validated individual-specific neurophysiological biomarkers during normal daily activities and used those patterns for adaptive deep brain stimulation (DBS). This technological approach may be widely applicable to brain disorders treatable by invasive neuromodulation.
Cognitive control impairments in healthy older adults may partly reflect disturbances in the ability to actively maintain goal-relevant information, a function that depends on the engagement of ...lateral prefrontal cortex (PFC). In 2 functional magnetic resonance imaging studies, healthy young and older adults performed versions of a task in which contextual cues provide goal-relevant information used to bias processing of subsequent ambiguous probes. In Study 1, a blocked design and manipulation of the cue–probe delay interval revealed a generalized pattern of enhanced task-related brain activity in older adults but combined with a specific delay-related reduction of activity in lateral PFC regions. In Study 2, a combined blocked/event-related design revealed enhanced sustained (i.e., across-trial) activity but a reduction in transient trial-related activation in lateral PFC among older adults. Further analyses of within-trial activity dynamics indicated that, within these and other lateral PFC regions, older adults showed reduced activation during the cue and delay period but increased activation at the time of the probe, particularly on high-interference trials. These results are consistent with the hypothesis that age-related impairments in goal maintenance abilities cause a compensatory shift in older adults from a proactive (seen in young adults) to a reactive cognitive control strategy.
The ClearPoint real-time interventional MRI-guided methodology for deep brain stimulation (DBS) lead placement may offer advantages to frame-based approaches and allow accurate implantation under ...general anesthesia. In this study, the authors assessed the safety and efficacy of DBS in Parkinson's disease (PD) using this surgical method.
This was a prospective single-center study of bilateral DBS therapy in patients with advanced PD and motor fluctuations. Symptom severity was evaluated at baseline and 12 months postimplantation using the change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III "off" medication score as the primary outcome variable.
Twenty-six PD patients (15 men and 11 women) were enrolled from 2010 to 2013. Twenty patients were followed for 12 months (16 with a subthalamic nucleus target and 4 with an internal globus pallidus target). The mean UPDRS Part III "off" medication score improved from 40.75 ± 10.9 to 24.35 ± 8.8 (p = 0.001). "On" medication time without troublesome dyskinesia increased 5.2 ± 2.6 hours per day (p = 0.0002). UPDRS Parts II and IV, total UPDRS score, and dyskinesia rating scale "on" medication scores also significantly improved (p < 0.01). The mean levodopa equivalent daily dose decreased from 1072.5 ± 392 mg to 828.25 ± 492 mg (p = 0.046). No significant cognitive or mood declines were observed. A single brain penetration was used for placement of all leads, and the mean targeting error was 0.6 ± 0.3 mm. There were 3 serious adverse events (1 DBS hardware-related infection, 1 lead fracture, and 1 unrelated death).
DBS leads placed using the ClearPoint interventional real-time MRI-guided method resulted in highly accurate lead placement and outcomes comparable to those seen with frame-based approaches.
To report long-term safety and efficacy outcomes of a large cohort of patients with medically refractory isolated dystonia treated with subthalamic nucleus (STN) deep brain stimulation (DBS).
Twenty ...patients (12 male, 8 female; mean age 49 ± 16.3 years) with medically refractory isolated dystonia were studied (14 were followed for 36 months). The primary endpoints were change in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor score and Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score at 36 months compared to preoperative baseline. Multiple secondary outcomes were also assessed (ClinicalTrials.gov NCT00773604).
Eighteen of 20 patients showed improvement 12 months after STN DBS with sustained benefit persisting for 3 years (n = 14). At 36 months, BFMDRS motor scores improved 70.4% from a mean 17.9 ± 8.5 to 5.3 ± 5.6 (p = 0.0002) and total TWSTRS scores improved 66.6% from a mean 41.0 ± 18.9 to 13.7 ± 17.9 (p = 0.0002). Improvement at 36 months was equivalent to that seen at 6 months. Disability and quality of life measures were also improved. Three hardware-related and 24 stimulation-related nonserious adverse events occurred between years 1 and 3 (including 4 patients with dyskinesia).
This study offers support for long-term tolerability and sustained effectiveness of STN DBS in the treatment of severe forms of isolated dystonia.
This study provides Class IV evidence that STN DBS decreases long-term dystonia severity in patients with medically refractory isolated dystonia.
Abstract
BACKGROUND:
Low-grade glioma (LGG) patients have increased life expectancy, so interest is high in the treatments that maximize cognition and quality of life.
OBJECTIVE:
To examine ...presurgical baseline cognitive deficits in a case series of LGG patients and determine cognitive effects of surgical resection with awake mapping.
METHODS:
We retrospectively assessed neurological deficits, subjective concerns from patient or caregiver, and cognitive deficits at baseline and postsurgery for 22 patients with newly diagnosed LGG who underwent baseline neuropsychological evaluation and magnetic resonance imaging before awake surgical resection with mapping. Twelve of the 22 patients returned for postoperative evaluation approximately 7 months after surgery.
RESULTS:
At baseline, 92% of patients/caregivers reported changes in cognition or mood. Neurological examinations and Montreal Cognitive Assessment Scale scores were largely normal; however, on many tests of memory and language, nearly half of individuals showed deficits. After surgery, 45% had no deficits on neurological examination, whereas 55% had only transient or mild difficulties. Follow-up neuropsychological testing found most performances stable to improved, particularly in language, although some patients showed declines on memory tasks.
CONCLUSION:
Most LGG patients in this series presented with normal neurological examinations and cognitive screening, but showed subjective cognitive and mood concerns and cognitive decline on neuropsychological testing, suggesting the importance of comprehensive evaluation. After awake mapping, language tended to be preserved, but memory demonstrated decline in some patients. These results highlight the importance of establishing a cognitive baseline before surgical resection and further suggest that awake mapping techniques provide reasonable language outcomes in individuals with LGG in eloquent regions.
OBJECT Diffusion MRI has uniquely enabled in vivo delineation of white matter tracts, which has been applied to the segmentation of eloquent pathways for intraoperative mapping. The last decade has ...also seen the development from earlier diffusion tensor models to higher-order models, which take advantage of high angular resolution diffusion-weighted imaging (HARDI) techniques. However, these advanced methods have not been widely implemented for routine preoperative and intraoperative mapping. The authors report on the application of residual bootstrap q-ball fiber tracking for routine mapping of potentially functional language pathways, the development of a system for rating tract injury to evaluate the impact on clinically assessed language function, and initial results predicting long-term language deficits following glioma resection. METHODS The authors have developed methods for the segmentation of 8 putative language pathways including dorsal phonological pathways and ventral semantic streams using residual bootstrap q-ball fiber tracking. Furthermore, they have implemented clinically feasible preoperative acquisition and processing of HARDI data to delineate these pathways for neurosurgical application. They have also developed a rating scale based on the altered fiber tract density to estimate the degree of pathway injury, applying these ratings to a subset of 35 patients with pre- and postoperative fiber tracking. The relationships between specific pathways and clinical language deficits were assessed to determine which pathways are predictive of long-term language deficits following surgery. RESULTS This tracking methodology has been routinely implemented for preoperative mapping in patients with brain gliomas who have undergone awake brain tumor resection at the University of California, San Francisco (more than 300 patients to date). In this particular study the authors investigated the white matter structure status and language correlation in a subcohort of 35 subjects both pre- and postsurgery. The rating scales developed for fiber pathway damage were found to be highly reproducible and provided significant correlations with language performance. Preservation of the left arcuate fasciculus (AF) and the temporoparietal component of the superior longitudinal fasciculus (SLF-tp) was consistent in all patients without language deficits (p < 0.001) at the long-term follow-up. Furthermore, in patients with short-term language deficits, the AF and/or SLF-tp were affected, and damage to these 2 pathways was predictive of a long-term language deficit (p = 0.005). CONCLUSIONS The authors demonstrated the successful application of q-ball tracking in presurgical planning for language pathways in brain tumor patients and in assessing white matter tract integrity postoperatively to predict long-term language dysfunction. These initial results predicting long-term language deficits following tumor resection indicate that postoperative injury to dorsal language pathways may be prognostic for long-term clinical language deficits. Study results suggest the importance of dorsal stream tract preservation to reduce language deficits in patients undergoing glioma resection, as well as the potential prognostic value of assessing postoperative injury to dorsal language pathways to predict long-term clinical language deficits.
Objective
Alzheimer's disease (AD) is found at autopsy in up to one third of patients with primary progressive aphasia (PPA), but clinical features that predict AD pathology in PPA are not well ...defined. We studied the relationships between language presentation, Aβ amyloidosis, and glucose metabolism in three PPA variants using 11C‐Pittsburgh compound B (11CPIB) and 18F‐labeled fluorodeoxyglucose positron emission tomography (18FFDG‐PET).
Methods
Patients meeting PPA criteria (N = 15) were classified as logopenic aphasia (LPA), progressive nonfluent aphasia (PNFA), or semantic dementia (SD) based on language testing. 11CPIB distribution volume ratios were calculated using Logan graphical analysis (cerebellar reference). 18FFDG images were normalized to pons. Partial volume correction was applied.
Results
Elevated cortical PIB (by visual inspection) was more common in LPA (4/4 patients) than in PNFA (1/6) and SD (1/5) (p < 0.02). In PIB‐positive PPA, PIB uptake was diffuse and indistinguishable from the pattern in matched AD patients (n = 10). FDG patterns were focal and varied by PPA subtype, with left temporoparietal hypometabolism in LPA, left frontal hypometabolism in PNFA, and left anterior temporal hypometabolism in SD. FDG uptake was significant asymmetric (favoring left hypometabolism) in PPA (p < 0.005) but not in AD.
Interpretation
LPA is associated with Aβ amyloidosis, suggesting that subclassification of PPA based on language features can help predict the likelihood of AD pathology. Language phenotype in PPA is closely related to metabolic changes that are focal and anatomically distinct between subtypes, but not to amyloid deposition patterns that are diffuse and similar to AD. Ann Neurol 2008
This study examined global resting‐state functional connectivity of neural oscillations in individuals with chronic tinnitus and normal and impaired hearing. We tested the hypothesis that distinct ...neural oscillatory networks are engaged in tinnitus with and without hearing loss. In both tinnitus groups, with and without hearing loss, we identified multiple frequency band‐dependent regions of increased and decreased global functional connectivity. We also found that the auditory domain of tinnitus severity, assayed by the Tinnitus Functional Index, was associated with global functional connectivity in both auditory and nonauditory regions. These findings provide candidate biomarkers to target and monitor treatments for tinnitus with and without hearing loss.
PDF
