Wendy Ringe

Magnetic resonance imaging of cerebellar–prefrontal and cerebellar–parietal functional connectivity

Recent studies of the cerebellum indicated its involvement in a diverse array of functions, and analyses of non-human primate neuroanatomy have revealed connections between cerebellum and cerebral cortex that might support cerebellar contributions to a wider range of functions than traditionally thought. These include cortico-ponto-cerebellar projections originating throughout cerebral cortex, in addition to projections from the dentate nucleus of the cerebellum to prefrontal and posterior parietal cortices via the thalamus. Such projections likely serve as important substrates for cerebellar involvement in human cognition, assuming their analogues are prominent in the human brain. These connections can be examined from a functional perspective through the use of functional connectivity MRI (FCMRI), a technique that allows the in vivo examination of coherence in MR signal among functionally related brain regions. Using this approach, low-frequency fluctuations in MR signal in the dentate nucleus correlated with signal fluctuations in cerebellar, thalamic, limbic, striatal, and cerebrocortical regions including parietal and frontal sites, with prominent coherence in dorsolateral prefrontal cortex. These findings indicate that FCMRI is a useful tool for examining functional relationships between the cerebellum and other brain regions, and they support the findings from non-human primate studies showing anatomic projections from cerebellum to regions of cerebral cortex with known involvement in higher cognitive functions. To our knowledge, this represents the first demonstration of functional coherence between the dentate nucleus and parietal and prefrontal cortices in the human brain, suggesting the presence of cerebellar-parietal and cerebellar-prefrontal functional connectivity.

Dyadic short forms of the Wechsler Adult Intelligence Scale-III.

Various short forms of the Wechsler Adult Intelligence Scale (WAIS)/WAIS-R have been developed to obtain estimates of overall intellectual level, although little research of WAIS-III short forms has been published to date. Full Scale IQ (FSIQ) estimates from four WAIS-III dyadic short forms were obtained by entering selected subtest scores from a mixed neurologic/psychiatric sample (n = 196) into regression equations. Results were cross validated on a second sample (n = 57). Within both samples, WAIS-III FSIQ scores were highly correlated (r = .90-.92, p < .001) with estimated FSIQ scores. Estimated FSIQ fell within 5 points of actual FSIQ in 49% to 74% of cross-validation cases and within 10 points of actual FSIQ in 81% to 93% of the sample. Comparable to findings from previous short-form investigations, actual and estimated FSIQ classification levels agreed in 46% to 67% of cases in the cross-validation sample. These dyadic WAIS-III forms appear appropriate for obtaining gross estimates of FSIQ in similar populations, although caution is recommended in interpreting estimated IQ scores.

Striatal functional connectivity networks are modulated by fMRI resting state conditions.

Resting state fluctuations in blood oxygenation level dependent functional connectivity magnetic resonance imaging (BOLD fcMRI) time-series have been increasingly employed to study functional connectivity networks in healthy and diseased brain. FcMRI studies have been conducted under a number of different conditions, including resting eyes open, visual fixation and finger tapping. BOLD fcMRI networks are believed to reflect both anatomically constrained spontaneous fluctuations and state-dependent activity. In this study, state-dependence of functional connectivity to dorsal and ventral striatum was assessed with fcMRI during an eyes open resting state condition (REST) and during continuous 3 Hz transcutaneous electrical nerve stimulation (TENS), with the a priori hypotheses: (1) dorsal striatum connectivity with sensorimotor/attention networks will be stronger during TENS compared to REST, (2) ventral striatum connectivity with limbic system emotion-processing network will be weaker during TENS compared to REST and (3) ventral striatum connectivity with sensorimotor/attention networks will be stronger during TENS compared to REST. These hypotheses were confirmed by the results obtained, indicating that resting state BOLD fMRI networks reflect, in substantial measure, state-dependent activity.

Validation of Non-Rigid Registration Between Functional and Anatomical Magnetic Resonance Brain Images

This paper presents a set of validation procedures for nonrigid registration of functional EPI to anatomical MRI brain images. Although various registration techniques have been developed and validated for high-resolution anatomical MRI images, due to a lack of quantitative and qualitative validation procedures, the use of nonrigid registration between functional EPI and anatomical MRI images has not yet been deployed in neuroimaging studies. In this paper, the performance of a robust formulation of a nonrigid registration technique is evaluated in a quantitative manner based on simulated data and is further evaluated in a quantitative and qualitative manner based on in vivo data as compared to the commonly used rigid and affine registration techniques in the neuroimaging software packages. The nonrigid registration technique is formulated as a second-order constrained optimization problem using a free-form deformation model and mutual information similarity measure. Bound constraints, resolution level and cross-validation issues have been discussed to show the degree of accuracy and effectiveness of the nonrigid registration technique. The analyses performed reveal that the nonrigid approach provides a more accurate registration, in particular when the functional regions of interest lie in regions distorted by susceptibility artifacts.

Pharmacological Enhancement of Aural Habilitation in Adult Cochlear Implant Users

Objective: The purpose of this report was to examine the preliminary data collected under a larger on-going feasibility study conducted with cochlear implant patients exploring the potential benefit of pharmacologically-enhanced aural rehabilitation therapy as a means of increasing speech tracking skills. Design: Eight adult cochlear implant participants participated in a randomized, double-blind study and received either 10 mg d-amphetamine (Treatment group, N = 4) or a placebo (Placebo group, N = 4) 60 minutes prior to a 1.5 hour intensive aural rehabilitation session occurring twice a week for two months. Treatment consisted of a multi-step rehabilitation program individualized for each participant to develop auditory-only speech tracking skills. Prior to and at the conclusion of the therapy sessions, SPECT rCBF imaging and speech tracking assessments were conducted. Results: Speech tracking scores of the placebo and treatment groups were similar before the aural habilitation intervention. In the placebo group, speech tracking performance increased 13.5% for visual plus auditory and auditory only presentations as a function of aural habilitation alone. The 10 mg d-amphetamine-facilitated program resulted in minimal increases in visual plus auditory tracking scores (2%) but led to a 43% increase for auditory-only speech tracking. Regional cerebral blood flow measures indicated no substantial improvement of brain activation in the placebo group while both the extent and magnitude of primary and associative auditory cortex activations increased significantly with the pharmacologically enhanced treatment program. Conclusions: These data support previous studies indicating an accelerated acquisition of speech and language abilities in stroke patients receiving traditional speech therapy in combination with d-amphetamine. Data, however, are preliminary and further study is warranted.

FMRI reveals abnormal central processing of sensory and pain stimuli in ill Gulf War veterans.

Many veterans chronically ill from the 1991 Gulf War exhibit symptoms of altered sensation, including chronic pain. In this study of 55 veterans of a Construction Battalion previously examined in 1995-1996 and 1997-1998, brain activation to innocuous and noxious heat stimuli was assessed in 2008-2009 with a quantitative sensory testing fMRI protocol in control veterans and groups representing three syndrome variants. Testing outside the scanner revealed no significant differences in warm detection or heat pain threshold among the four groups. In the fMRI study, Syndrome 1 and Syndrome 2, but not Syndrome 3, exhibited hypo-activation to innocuous heat and hyper-activation to noxious heat stimuli compared to controls. The results indicate abnormal central processing of sensory and painful stimuli in 2 of 3 variants of Gulf War illness and call for a more comprehensive study with a larger, representative sample of veterans.

Neural bases of the foreign accent syndrome: a functional magnetic resonance imaging case study.

Foreign accent syndrome (FAS) is a rare disorder characterized by the emergence of a perceived foreign accent following brain damage. Despite decades of study, little is known about the neural substrates involved in this disorder. In this case study, MRI images of the brain were obtained during a speech task for an American English-speaking monolingual female who presented with FAS of unknown etiology and was thought to sound ‘Swedish’ or ‘Eastern European’. On the basis of MR structural imaging, the patient was noted to have frontal lobe atrophy. An fMRI picture-naming task designed to broadly engage the speech motor network revealed predominantly left-hemisphere involvement, including activation of the (1) left superior temporal and medial frontal structures, (2) bilateral subcortical structures and thalamus, and (3) left cerebellum. The results suggest an instance of substantial brain reorganization for speech motor control.

Single Neuropsychological Test Scores Associated With Rate of Cognitive Decline in Early Alzheimer Disease

Alzheimer disease (AD) characteristically begins with episodic memory impairment followed by other cognitive deficits; however, the course of illness varies, with substantial differences in the rate of cognitive decline. For research and clinical purposes it would be useful to distinguish between persons who will progress slowly from persons who will progress at an average or faster rate. Our objective was to use neurocognitive performance features and disease-specific and health information to determine a predictive model for the rate of cognitive decline in participants with mild AD. We reviewed the records of a series of 96 consecutive participants with mild AD from 1995 to 2011 who had been administered selected neurocognitive tests and clinical measures. Based on Clinical Dementia Rating (CDR) of functional and cognitive decline over 2 years, participants were classified as Faster (n = 45) or Slower (n = 51) Progressors. Stepwise logistic regression analyses using neurocognitive performance features, disease-specific, health, and demographic variables were performed. Neuropsychological scores that distinguished Faster from Slower Progressors included Trail Making Test - A, Digit Symbol, and California Verbal Learning Test (CVLT) Total Learned and Primacy Recall. No disease-specific, health, or demographic variable predicted rate of progression; however, history of heart disease showed a trend. Among the neuropsychological variables, Trail Making Test - A best distinguished Faster from Slower Progressors, with an overall accuracy of 68%. In an omnibus model including neuropsychological, disease-specific, health, and demographic variables, only Trail Making Test - A distinguished between groups. Several neuropsychological performance features were associated with the rate of cognitive decline in mild AD, with baseline Trail Making Test - A performance best separating those who declined at an average or faster rate from those who showed slower progression.

Differential activation on fMRI of monozygotic twins discordant for AD

This is the first report of fMRI in monozygotic twins discordant for AD. FMRI brain activation patterns were examined during visuospatial and verbal working memory tasks. The affected twin had greater parietal involvement bilaterally during both working memory tasks and reduced left dorsolateral prefrontal cortex activity on the visuospatial memory task. Thus, fMRI may identify additional brain regions recruited in patients with AD to perform a given cognitive task.

Dyadic Short Forms of the Wechsler Adult Intelligence Scale-IV

Full Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) administration can be time-consuming and may not be necessary when intelligence quotient estimates will suffice. Estimated Full Scale Intelligence Quotient (FSIQ) and General Ability Index (GAI) scores were derived from nine dyadic short forms using individual regression equations based on data from a clinical sample (n = 113) that was then cross validated in a separate clinical sample (n = 50). Derived scores accounted for 70%-83% of the variance in FSIQ and 77%-88% of the variance in GAI. Predicted FSIQs were strongly associated with actual FSIQ (rs = .73-.88), as were predicted and actual GAIs (rs = .80-.93). Each of the nine dyadic short forms of the WAIS-IV was a good predictor of FSIQ and GAI in the validation sample. These data support the validity of WAIS-IV short forms when time is limited or lengthier batteries cannot be tolerated by patients.