Sule Tinaz

Compromised fronto-striatal functioning in HIV: an fMRI investigation of semantic event sequencing.

The human immunodeficiency virus (HIV) damages fronto-striatal regions, and is associated with deficits in executive functioning. We recently developed a semantic event sequencing task based on the Picture Arrangement subtest of the Wechsler Adult Intelligence Scale-III for use with functional magnetic resonance imaging (fMRI) and found recruitment of dorsolateral prefrontal cortex and basal ganglia in healthy participants. To assess the impact of HIV on the functioning of the basal ganglia and prefrontal cortex, we administered this task to 11 HIV+ and 11 Control participants matched for age and education. Neuropsychological evaluation demonstrated that the HIV+ group had mild impairment in memory retrieval and motor functioning, but was not demented. Morphometric measurements suggested no atrophy in basal ganglia regions. The results of the fMRI analysis revealed hypoactivation of the left caudate, left dorsolateral prefrontal cortex, and bilateral ventral prefrontal cortex in the HIV+ group. Functional connectivity analysis demonstrated less functional connectivity between the caudate and prefrontal cortex and basal ganglia regions in the HIV+ group. In contrast, the HIV+ group demonstrated increased activation of right postcentral/supramarginal gyrus, and greater connectivity between the caudate and this same anterior parietal region. The results of this study extend previous investigations by demonstrating compromised function of the caudate and connected prefrontal regions in HIV during cognition. This disruption of fronto-striatal circuitry likely precedes the development of cognitive impairment in HIV.

Focal Cortical and Subcortical Atrophy in Early Parkinson’s Disease

Neurodegeneration in clinically manifest Parkinsons disease affects the substantia nigra pars compacta, and gradually spreads to the limbic cortices and the neocortex. We used MRI imaging coupled with automated surface reconstruction and segmentation methods to examine cortical thickness and subcortical volumes in nondemented, early‐stage Parkinsons disease patients compared to matched healthy control participants. These methods, which have been previously used to document cortical thickness changes in patients with Alzheimers disease and Huntingtons disease but not Parkinsons disease, use MR signal intensity information and the geometric constraints of the cortical and subcortical structures for an accurate tissue classification. Parkinsons disease patients were matched to the control group in psychomotor processing speed and executive functioning, but showed higher anxiety state scores. Our results demonstrated focal cortical thinning in the Parkinsons disease group in the orbitofrontal cortex, ventrolateral prefrontal cortex, and occipito‐parietal areas. Subcortically, striatal volume loss was noted. These results demonstrate that both cortical and subcortical structural changes occur at relatively early stages of the disease, and are discussed in terms of the emotional dysregulation that occurs early on in patients with Parkinsons disease.

Risk factors for Alzheimer disease: a population-based case-control study in Istanbul, Turkey.

The objective is to study risk factors for Alzheimer disease (AD) in Istanbul, Turkey. This is a population-based case-control study. We screened people over age 70 in the community for cognitive impairment. The screen positives and a proportion of screen negatives underwent neurologic examination in the second phase. Cases were 57 “probable” AD patients and controls were 127 cognitively normal individuals identified by neurologic examination. Odds ratios (OR) were calculated using multivariate logistic regression analysis. Having a university/college degree had a protective effect on AD risk (OR = 0.10, 95% confidence interval [CI] = 0.02–0.50). Exposure to occupational electromagnetic field had an OR of 4.02 (95% CI = 1.02–15.78). Use of electricity for residential heating also showed elevated risk (OR = 2.77, 95% CI = 1.12–6.85). Our results suggest that having a higher education is protective from AD and that electromagnetic field exposure at work or at home is a significant risk factor.

Delayed match to object or place: An event-related fMRI study of short-term stimulus maintenance and the role of stimulus pre-exposure

Recent delayed matching studies have demonstrated that maintaining trial-unique stimuli in working memory modulates activity in temporal lobe structures. In contrast, most previous studies that focused on the role of the prefrontal cortex (PFC) used familiar stimuli. We combined fMRI with a delayed-match-to-sample (DMS) task in humans that allowed us to manipulate stimulus pre-exposure (trial-unique vs. familiar objects) and stimulus domain (object vs. location). A visually guided saccade task was used to localize the frontal eye fields (FEF). We addressed two questions: First, we examined whether delay-period activity within PFC regions was more strongly engaged when stimuli were familiar (pre-exposed) than when they were not seen previously (trial-unique). Second, we examined the role of regions within the PFC in object vs. location working memory. Subjects were instructed to remember one stimulus domain while ignoring the other over an 8-s delay period. Object-specific delay-period activity was greatest in the posterior orbitofrontal cortex (OFC) bilaterally, and was stronger for familiar than trial-unique objects. In addition, consistent with previous findings, right posterior superior frontal sulcus, and the FEF were specifically active during the delay period of the location DMS task. These activations outside FEF were not related to saccadic eye movements. In contrast to previous reports, object-specific delay activity was more prominent in the posterior OFC than in the ventrolateral PFC, and was found to be greater for familiar than for trial-unique objects. These results suggest a critical role for the orbitofrontal cortex for maintaining object information in working memory.

Evidence for the importance of basal ganglia output nuclei in semantic event sequencing: an fMRI study.

Semantic event sequencing is the ability to plan ahead and order meaningful events chronologically. To investigate the neural systems supporting this ability, an fMRI picture sequencing task was developed. Participants sequenced a series of four pictures presented in random order based on the temporal relationship among them. A control object discrimination task was designed to be comparable to the sequencing task regarding semantic, visuospatial, and motor processing requirements but without sequencing demands. fMRI revealed significant activation in the dorsolateral prefrontal cortex and globus pallidus internal part in the picture sequencing task compared with the control task. The findings suggest that circuits involving the frontal lobe and basal ganglia output nuclei are important for picture sequencing and more generally for the sequential ordering of events. This is consistent with the idea that the basal ganglia output nuclei are critical not only for motor but also for high-level cognitive function, including behaviors involving meaningful information. We suggest that the interaction between the frontal lobes and basal ganglia output nuclei in semantic event sequencing can be generalized to include the sequential ordering of behaviors in which the selective updating of neural representations is the key computation.

Role of the sensorimotor cortex in tourette syndrome using multimodal imaging

Tourette syndrome (TS) is a neuropsychiatric disorder characterized by motor and vocal tics. Most patients describe uncomfortable premonitory sensations preceding the tics and a subjective experience of increased sensitivity to tactile stimuli. These reports indicate that a sensory processing disturbance is an important component of TS together with motor phenomena. Thus, we focused our investigation on the role of the sensorimotor cortex (SMC) in TS using multimodal neuroimaging techniques. We measured the gamma‐aminobutyric acid (GABA)+/Creatine (Cre) ratio in the SMC using GABA 1H magnetic resonance spectroscopy. We recorded the baseline beta activity in the SMC using magnetoencephalography and correlated GABA+/Cre ratio with baseline beta band power. Finally, we examined the resting state functional connectivity (FC) pattern of the SMC using functional magnetic resonance imaging (fMRI). GABA+/Cre ratio in the SMC did not differ between patients and controls. Correlation between the baseline beta band power and GABA+/Cre ratio was abnormal in patients. The anterior insula showed increased FC with the SMC in patients. These findings suggest that altered limbic input to the SMC and abnormal GABA‐mediated beta oscillations in the SMC may underpin some of the sensorimotor processing disturbances in TS and contribute to tic generation. Hum Brain Mapp 35:5834–5846, 2014. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Role of the right dorsal anterior insula in the urge to tic in tourette syndrome

The mid‐posterior part of the insula is involved in processing bodily sensations and urges and is activated during tic generation in Tourette syndrome. The dorsal anterior part of the insula, however, integrates sensory and emotional information with cognitive valuation and is implicated in interoception. The right dorsal anterior insula also participates in urge suppression in healthy subjects. This study examined the role of the right dorsal anterior insula in the urge to tic in Tourette syndrome.

Repetitive Transcranial Magnetic Stimulation in Cervical Dystonia: Effect of Site and Repetition in a Randomized Pilot Trial

Dystonia is characterized by abnormal posturing due to sustained muscle contraction, which leads to pain and significant disability. New therapeutic targets are needed in this disorder. The objective of this randomized, sham-controlled, blinded exploratory study is to identify a specific motor system target for non-invasive neuromodulation and to evaluate this target in terms of safety and tolerability in the cervical dystonia (CD) population. Eight CD subjects were given 15-minute sessions of low-frequency (0.2 Hz) repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (MC), dorsal premotor cortex (dPM), supplementary motor area (SMA), anterior cingulate cortex (ACC) and a sham condition with each session separated by at least two days. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score was rated in a blinded fashion immediately pre- and post-intervention. Secondary outcomes included physiology and tolerability ratings. The mean change in TWSTRS severity score by site was 0.25 ± 1.7 (ACC), -2.9 ± 3.4 (dPM), -3.0 ± 4.8 (MC), -0.5 ± 1.1 (SHAM), and -1.5 ± 3.2 (SMA) with negative numbers indicating improvement in symptom control. TWSTRS scores decreased from Session 1 (15.1 ± 5.1) to Session 5 (11.0 ± 7.6). The treatment was tolerable and safe. Physiology data were acquired on 6 of 8 subjects and showed no change over time. These results suggest rTMS can modulate CD symptoms. Both dPM and MC are areas to be targeted in further rTMS studies. The improvement in TWSTRS scores over time with multiple rTMS sessions deserves further evaluation. Trial Registration ClinicalTrials.gov NCT01859247

Alcohol challenge and sensitivity to change of the essential tremor rating assessment scale

The ability of the Essential Tremor (ET) Rating Assessment Scale (TETRAS) to detect changes in tremor severity is unknown.

Changes in functional organization and white matter integrity in the connectome in Parkinson's disease.

Parkinsons disease (PD) leads to dysfunction in multiple cortico-striatal circuits. The neurodegeneration has also been associated with impaired white matter integrity. This structural and functional “disconnection” in PD needs further characterization. We investigated the structural and functional organization of the PD whole brain connectome consisting of 200 nodes using diffusion tensor imaging and resting-state functional MRI, respectively. Data from 20 non-demented PD patients on dopaminergic medication and 20 matched controls were analyzed using graph theory-based methods. We focused on node strength, clustering coefficient, and local efficiency as measures of local network properties; and network modularity as a measure of information flow. PD patients showed reduced white matter connectivity in frontoparietal-striatal nodes compared to controls, but no change in modular organization of the white matter tracts. PD group also showed reduction in functional local network metrics in many nodes distributed across the connectome. There was also decreased functional modularity in the core cognitive networks including the default mode and dorsal attention networks, and sensorimotor network, as well as a lack of modular distinction in the orbitofrontal and basal ganglia nodes in the PD group compared to controls. Our results suggest that despite subtle white matter connectivity changes, the overall structural organization of the PD connectome remains robust at relatively early disease stages. However, there is a breakdown in the functional modular organization of the PD connectome.