Mild traumatic brain injury (mTBI), also referred to as concussion, remains a controversial diagnosis because the brain often appears quite normal on conventional computed tomography (CT) and magnetic resonance imaging (MRI) scans. Such conventional tools, however, do not adequately depict brain injury in mTBI because they are not sensitive to detecting diffuse axonal injuries (DAI), also described as traumatic axonal injuries (TAI), the major brain injuries in mTBI. Furthermore, for the 15 to 30% of those diagnosed with mTBI on the basis of cognitive and clinical symptoms, i.e., the “miserable minority,” the cognitive and physical symptoms do not resolve following the first three months post-injury. Instead, they persist, and in some cases lead to long-term disability. The explanation given for these chronic symptoms, i.e., postconcussive syndrome, particularly in cases where there is no discernible radiological evidence for brain injury, has led some to posit a psychogenic origin. Such attributions are made all the easier since both post-traumatic stress disorder (PTSD) and depression are frequently co-morbid with mTBI. The challenge is thus to use neuroimaging tools that are sensitive to DAI/TAI, such as diffusion tensor imaging (DTI), in order to detect brain injuries in mTBI. Of note here, recent advances in neuroimaging techniques, such as DTI, make it possible to characterize better extant brain abnormalities in mTBI. These advances may lead to the development of biomarkers of injury, as well as to staging of reorganization and reversal of white matter changes following injury, and to the ability to track and to characterize changes in brain injury over time. Such tools will likely be used in future research to evaluate treatment efficacy, given their enhanced sensitivity to alterations in the brain. In this article we review the incidence of mTBI and the importance of characterizing this patient population using objective radiological measures. Evidence is presented for detecting brain abnormalities in mTBI based on studies that use advanced neuroimaging techniques. Taken together, these findings suggest that more sensitive neuroimaging tools improve the detection of brain abnormalities (i.e., diagnosis) in mTBI. These tools will likely also provide important information relevant to outcome (prognosis), as well as play an important role in longitudinal studies that are needed to understand the dynamic nature of brain injury in mTBI. Additionally, summary tables of MRI and DTI findings are included. We believe that the enhanced sensitivity of newer and more advanced neuroimaging techniques for identifying areas of brain damage in mTBI will be important for documenting the biological basis of postconcussive symptoms, which are likely associated with subtle brain alterations, alterations that have heretofore gone undetected due to the lack of sensitivity of earlier neuroimaging techniques. Nonetheless, it is noteworthy to point out that detecting brain abnormalities in mTBI does not mean that other disorders of a more psychogenic origin are not co-morbid with mTBI and equally important to treat. They arguably are. The controversy of psychogenic versus physiogenic, however, is not productive because the psychogenic view does not carefully consider the limitations of conventional neuroimaging techniques in detecting subtle brain injuries in mTBI, and the physiogenic view does not carefully consider the fact that PTSD and depression, and other co-morbid conditions, may be present in those suffering from mTBI. Finally, we end with a discussion of future directions in research that will lead to the improved care of patients diagnosed with mTBI.
Mild Traumatic Brain Injury; mTBI; TBI; Diffusion Tensor Imaging; DTI; Magnetic Resonance Imaging; MRI; Diffusion-Weighted Imaging; DWI; Susceptibility-Weighted Imaging; SWI; Signature Injury of War; Concussion; Postconcussive syndrome; Postconcussive Symptoms; Complicated mTBI; Uncomplicated mTBI; Physiogenesis; Psychogenesis; Miserable Minority
There is need for a valid and reliable biomarker for HIV Associated Neurocognitive Disorder (HAND). The purpose of the present study was to provide preliminary evidence of the potential utility of neuronal functional connectivity measures obtained using magnetoencephalography (MEG) to identify HIV-associated changes in brain function. Resting state, eyes closed, MEG data from 10 HIV-infected individuals and 8 seronegative controls were analyzed using mutual information (MI) between all pairs of MEG sensors to determine whether there were functional brain networks that distinguished between subject groups based on cognition (global and learning) or on serostatus.
Three networks were identified across all subjects, but after permutation testing (at α < .005) only the one related to HIV serostatus was significant. The network included MEG sensors (planar gradiometers) above the right anterior region connecting to sensors above the left posterior region. A mean MI value was calculated across all connections from the anterior to the posterior groupings; that score distinguished between the serostatus groups with only one error (sensitivity = 1.00, specificity = .88 (X2 = 15.4, df = 1, p < .01, Relative Risk = .11). There were no significant associations between the MI value and the neuropsychological Global Impairment rating, substance abuse, mood disorder, age, education, CD4+ cell counts or HIV viral load.
We conclude that using a measure of functional connectivity, it may be possible to distinguish between HIV-infected and uninfected individuals, suggesting that MEG may have the potential to serve as a sensitive, non-invasive biomarker for HAND.
HIV Disease; Cognition; Magnetoencephalography; Functional Connectivity
Complex skill learning at a joint initiates competition between its representation in the primary motor cortex (M1) and that of the neighboring untrained joint. This process of representational plasticity has been mapped by cortically-evoking simple movements. We investigated, following skill learning at a joint, 1) whether comparable processes of representational plasticity are observed when mapping is based on volitionally produced complex movements and 2) the consequence on the skill of the adjacent untrained joint. Twenty-four healthy subjects were assigned to either finger- or elbow-skill training or no-training control group. At pretest and posttest, subjects performed complex skill movements at finger, elbow and ankle concurrent with functional magnetic resonance imaging (fMRI) to define learning and allow mapping of corresponding activation-based representations in M1. Skill following both finger- and elbow- training transferred to the ankle (remote joint) (p=0.05 and 0.05); however, finger training did not transfer to the elbow and elbow training did not transfer to the finger. Following finger training, location of the trained finger representation showed a trend (p=0.08) for medial shift towards the representation of adjacent untrained elbow joint; the change in intensity of the latter representation was associated with elbow skill (Spearman's ρ=–0.71, p=0.07). Following elbow training, the trained elbow representation and the adjacent untrained finger representation increased their overlap (p=0.02), which was associated with finger skill (Spearman's ρ=–0.83, p=0.04). Thus, our pilot study reveals comparable processes of representational plasticity with fMRI mapping of complex skill movements as have been demonstrated with cortically-evoked methods. Importantly, these processes may limit the degree of transfer of skill between trained and adjacent untrained joints. These pilot findings that await confirmation in large-scale studies have significant implications for neuro-rehabilitation. For instance, techniques, such as motor cortical stimulation, that can potentially modulate processes of representational plasticity between trained and adjacent untrained representations, may optimize transfer of skill.
Motor cortex; Learning; Skill; Representation; Plasticity; functional Magnetic Resonance Imaging (fMRI)
Corpus callosum (CC) area abnormalities have been reported in magnetic resonance imaging (MRI) studies of adults and youths with bipolar disorder (BPD), suggesting interhemispheric communication may be abnormal in BPD and may be present early in the course of illness and affect normal neuromaturation of this structure throughout the lifecycle. Neuroimaging scans from 44 youths with DSM-IV BPD and 22 healthy controls (HC) were analyzed using cross-sectional area measurements and a novel method of volumetric parcellation. Univariate analyses of variance were conducted on CC subregions using both volume and traditional area measurements. Youths with BPD had smaller middle and posterior callosal regions, and reduced typical age-related increases in CC size. The cross-sectional area and novel volumetric methodologies resulted in similar findings. Future longitudinal assessments of CC development would track the evolution of callosal abnormalities in youths with BPD and allow exploration of the functional significance of these findings.
Bipolar disorder; Corpus callosum; Neuroimaging; Youths; MRI
Traumatic brain injury (TBI) and orthopedic injury (OI) patients are prone to anxiety and mood disorders. In the present study, we integrated anatomical and diffusion tensor neuroimaging to investigate structural properties of the amygdala and hippocampus, gray matter regions implicated in anxiety and mood disorders. Children and adolescents were evaluated during the late sub-acute phase of recovery following trauma resulting from either moderate to severe TBI or OI. Mean diffusivity (MD) of the amygdala and hippocampus was elevated following TBI. An interaction of hemisphere, structure, and group revealed that MD of the right amygdala was elevated in females with TBI. Self-reported anxiety scores were not related to either volume or microstructure of the hippocampus, or to volume or fractional anisotropy of the amygdala. Left amygdala MD in the TBI group accounted for 17.5% of variance in anxiety scores. Anxiety symptoms may be mediated by different mechanisms in patients with TBI or OI.
Anxiety; Amygdala; DTI; TBI; Children
Blood oxygenation level- dependent (BOLD) and cerebral blood flow (CBF)-based functional magnetic resonance imaging (fMRI) were used to measure primary visual cortex responses to photic stimulation in 23 children (12.4 ± 0.7 years old) with sickle cell anemia (SCA) and 21 clinical controls (11 ± 1.0 years old). The objectives were to investigate the effect of SCA on detection of brain activation with fMRI and to explore the relationship between fMRI responses and global cognitive function. The BOLD responses were diminished in children with SCA. Clinical indicators of disease severity were greatest in patients without detectable visual cortex activation, but blood hemoglobin concentration and resting CBF were not predictive of BOLD signal amplitude in the SCA patients. Unexpectedly, the BOLD signal amplitude was positively associated (rs≥0.8, p≤0.05) with Wechsler Abbreviated Scale of Intelligence scores, suggesting that fMRI may help clarify medical, hemodynamic, and neural factors that mediate adverse effects of SCA on neurocognitive function.
sickle cell anemia; functional magnetic resonance imaging; brain activation; cognitive function; blood oxygenation level- dependent; cerebral blood flow
The goal of the current study was to examine cognitive change in both healthy controls (n=229) and individuals with mild cognitive impairment (MCI) (n=397) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We applied latent growth modeling to examine baseline and longitudinal change over 36 months in five cognitive factors derived from the ADNI neuropsychological test battery (memory, executive function/processing speed, language, attention and visuospatial). At baseline, MCI patients demonstrated lower performance on all of the five cognitive factors when compared to controls. Both controls and MCI patients declined on memory over 36 months; however, the MCI patients declined at a significantly faster rate than controls. The MCI patients also declined over 36 months on the remaining four cognitive factors. In contrast, the controls did not exhibit significant change over 36 months on the non-memory cognitive factors. Within the MCI group, executive function declined faster than memory, while the other factor scores changed slower than memory over time. These findings suggest different patterns of cognitive change in healthy older adults and MCI patients. The findings also suggest that, when compared with memory, executive function declines faster than other cognitive factors in patients with MCI. Thus, decline in non-memory domains may be an important feature for distinguishing healthy older adults and persons with MCI.
ADNI; Neuropsychology; Cognition; Mild cognitive impairment; Cognitive change; Executive function
Children treated with cranial irradiation for brain tumors have reduced white matter volume and deficits in reading ability. This study prospectively examined the relationship between reading and white matter integrity within this patient group.
Patients (n=54) were treated with post-surgical radiation followed by 4 cycles of high-dose chemotherapy with stem cell support. At 12 months post-diagnosis, all patients completed a neuropsychology evaluation and a diffusion tensor imaging (DTI) exam. White matter integrity was determined through measures of fractional anisotropy (FA).
Significant group differences in FA were found between above average readers and below average readers within the left and right posterior limb of the internal capsule, and right knee of the internal capsule with a trend within the left temporal-occipital region.
The integrity of the white matter in these regions may affect communication among visual, auditory, and language cortical areas that are engaged during reading.
diffusion tensor imaging; reading; pediatric brain tumors
Cardiovascular disease (CVD) is associated with cognitive deficits even in the absence of stroke. We examined the relationship between cardiac performance, as measured by cardiac output (CO) and ejection fraction (EF), and brain activity during a verbal working memory (VWM) task in elderly CVD patients who tend to be at increased risk for vascular cognitive impairments. Seventeen patients were recruited from a cohort participating in an ongoing prospective study examining the effects of CVD on cognitive function in the elderly. Participants were diagnosed with CVD (age 68±8) and completed a 2-back VWM task in a 1.5T fMRI paradigm. CO and EF were calculated from echocardiogram measures. Task-related activation was averaged in a priori regions of interest. The relationship between CO, EF, and 2-back-related activity was modeled using partial correlations (two-tailed p<.05) controlling for age and 2-back accuracy. All participants were globally cognitively intact as indicated by Mini-Mental Status Exam and Dementia Rating Scale scores. Mean accuracy on the 2-back was 78±9% while reaction time averaged 1,027±192 ms. Mean CO and EF values showed a large range (CO: 3.55 to 6.31; EF: 0.36 to 0.76) but average values were within the normal range. After controlling for age and 2-back accuracy, lower EF was related to decrease in left insula activity (r=0.61, p=0.03). There were trends for EF to be related to accuracy (r=0.47, p=0.09) and reaction time (r=−0.48, p=0.09). CO was also related to insula activity (r=0.60, p=0.04) and activity in the supplementary motor area activity (r=0.66, p=0.01). Cardiac performance was related to decreased efficiency in task related brain areas and tended to be related to performance on a VWM task in elderly patients with CVD. Results have implications for a line of investigation indicating that cardiac and systemic vascular indices could be used as proxy measures to examine mechanisms of cerebrovascular dysfunction in the elderly.
Functional magnetic resonance imaging; FMRI; Functional neuroimaging; Verbal working memory; Cardiovascular disease; Heart disease; Ejection fraction; Cardiac output
Child and adolescent psychiatric neuroimaging research typically lags behind similar advances in adult disorders. While the pediatric depression imaging literature is less developed, a recent surge in interest has created the need for a synthetic review of this work. Major findings from pediatric volumetric and functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI) and resting state functional connectivity studies converge to implicate a corticolimbic network of key areas that work together to mediate the task of emotion regulation. Imaging the brain of children and adolescents with unipolar depression began with volumetric studies of isolated brain regions that served to identify key prefrontal, cingulate and limbic nodes of depression-related circuitry elucidated from more recent advances in DTI and functional connectivity imaging. Systematic review of these studies preliminarily suggests developmental differences between findings in youth and adults, including prodromal neurobiological features, along with some continuity across development.
pediatric depression; major depressive disorder; adolescents; neuroimaging; MRI brain imaging; fMRI
Although [18F]fluoro-L-dopa [FDOPA] positron emission tomography (PET) has been used as a surrogate outcome measure in Parkinson's disease therapeutic trials, this biomarker has not been proven to reflect clinical status longitudinally. We completed a retrospective analysis of relationships between computerized sampling of motor performance, FDOPA PET, and clinical outcome scales, repeated over 4 years, in 26 Parkinson's disease (PD) patients and 11 healthy controls. Mixed effects analyses showed that movement time and tongue strength best differentiated PD from control subjects. In the treated PD cohort, motor performance measures changed gradually in contrast to a steady decline in striatal FDOPA uptake. Prolonged reaction and movement time were related to lower caudate nucleus FDOPA uptake, and abnormalities in hand fine force control were related to mean striatal FDOPA uptake. These findings provide evidence that regional loss of nigrostriatal inputs to frontostriatal networks affects specific aspects of motor function.
Fluorodopa; motor control; Parkinson's disease; positron emission tomography; ageing; Tongue/*physiopathology; Facial Muscles/*physiopathology
Age has a multifaceted impact on neural measures which are not always directly related to alterations in clinical and cognitive measures. This partial protection from the deleterious effects of age in some individuals is referred to as cognitive reserve (CR) and although linked to variations in intelligence and life experiences, its mechanism is still unclear. Within the framework of a theoretical model we tested two potential mechanistic roles of CR to maintain task performance, neural reserve and neural compensation, in young and older adults using functional and structural MRI. Neural reserve refers to increased efficiency and/or capacity of existing functional neural resources. Neural compensation refers to the increased ability to recruit new, additional functional resources. Using structural and functional measures and task performance, the roles of CR were tested using path analysis. Results supported both mechanistic theories of CR and the use of our general theoretical model.
Aging; cognitive reserve; multi-modal neuroimaging; path analysis; function; structure
The purpose of this study was to determine the pattern and extent of caudate nucleus and putamen atrophy in HIV-infected men with well-controlled immune status and viral replication. 155 men underwent structural brain magnetic resonance imaging; 84 were HIV-infected and 71 were uninfected controls. MRI data were processed using the Fully Deformable Segmentation routine, producing volumes for the right and left caudate nucleus and putamen, and 3-D maps of spatial patterns of thickness. There was significant atrophy in the HIV-infected men in both the caudate and putamen, principally in the anterior regions. The volume of the basal ganglia was inversely associated with the time since first seropositivity, suggesting that either there is a chronic, subclinical process that continues in spite of therapy, or that the extent of the initial insult caused the extent of atrophy.
HIV; MRI; Gray matter; Basal ganglia
The present study examined the relationship between entorhinal cortex and hippocampal volume with fMRI activation during episodic memory function in elderly controls with no cognitive impairment and individuals with amnesic mild cognitive impairment (aMCI). Both groups displayed limited evidence for a relationship between hippocampal volume and fMRI activation. Smaller right entorhinal cortex volume was correlated with reduced activation in left and right medial frontal cortex (BA 8) during incidental encoding for both aMCI and elderly controls. However, during recognition, smaller left entorhinal cortex volume correlated with reduced activation in right BA 8 for the control group, but greater activation for the aMCI group. There was no significant relationship between entorhinal cortex volume and activation during intentional encoding in either group. The recognition-related dissociation in structure/function relationships in aMCI paralleled our behavioral findings, where individuals with aMCI displayed poorer performance relative to controls during recognition, but not encoding. Taken together, these results suggest that the relationship between entorhinal cortex volume and fMRI activation during episodic memory function is altered in individuals with aMCI.
recognition; medial temporal lobe; frontal cortex; intentional encoding; incidental encoding; fMRI
Postural instability occurs in HIV infection, but quantitative balance tests in conjunction with neuroimaging are lacking. We examined whether infratentorial brain tissue volume would be deficient in nondemented HIV-infected individuals and whether selective tissue deficits would be related to postural stability and psychomotor speed performance. The 123 participants included 28 men and 12 women with HIV infection without dementia or alcohol use disorders, and 40 men and 43 women without medical or psychiatric conditions. Participants completed quantitative balance testing, Digit Symbol test, and a test of finger movement speed and dexterity. An infratentorial brain region, supratentorial ventricular system, and corpus callosum were quantified with MRI-derived atlas-based parcellation, and together with archival DTI-derived fiber tracking of pontocerebellar and internal and external capsule fiber systems, brain measures were correlated with test performance. The tissue ratio of the infratentorium was ~3% smaller in the HIV than control group. The HIV group exhibited performance deficits in balancing on one foot, walking toe-to-heel, Digit Symbol substitution task, and time to complete all Digit Symbol grid boxes. Total infratentorial tissue ratio was a significant predictor of balance and Digit Symbol scores. Balance scores did not correlate significantly with ventricular volumes, callosal size, or internal or external capsule fiber integrity but did so with indices of pontocerebellar tract integrity. HIV-infected individuals specifically recruited to be without complications from alcohol use disorders had pontocerebellar tissue volume deficits with functional ramifications. Postural stability and psychomotor speed were impaired and attributable, at least in part, to compromised infratentorial brain systems.
MRI; DTI; Cerebellum; Pons; Vermis; Gait; Postural stability; HIV infection; Motor speed; Dexterity; Falling; Ataxia
Dementia with Lewy bodies (DLB) is often associated with occipital hypometabolism or hypoperfusion, as well as deficits in cholinergic neurotransmission. In this study, 11 mild DLB, 16 mild AD and 16 age-matched controls underwent arterial spin-labeled perfusion MRI (ASL-pMRI) and neuropsychological testing. Patterns of cerebral blood flow (CBF) and cognitive performance were compared. In addition, combined ASL-pMRI and ChEI drug challenge (pharmacologic MRI) was tested as a probe of cholinergic function in 4 of the DLB participants. Frontal and parieto-occipital hypoperfusion was observed in both DLB and AD but was more pronounced in DLB. Following ChEI treatment, perfusion increased in temporal and parieto-occipital cortex, and cognitive performance improved on a verbal fluency task. If confirmed in a larger study, these results provide further evidence for brain cholinergic dysfunction in DLB pathophysiology, and use of pharmacologic MRI as an in vivo measure of cholinergic function.
Arterial spin-labeled perfusion MRI; Pharmacologic MRI; Dementia with Lewy bodies; Cholinesterase inhibitors
Amyloid imaging with [11C]Pittsburgh Compound-B (PiB) provides in vivo data on plaque deposition in those with, or at risk for, Alzheimer’s disease (AD). We performed a gene-based association analysis of 15 quality-controlled amyloid-pathway associated candidate genes in 103 Alzheimer’s Disease Neuroimaging Initiative participants. The mean normalized PiB uptake value across four brain regions known to have amyloid deposition in AD was used as a quantitative phenotype. The minor allele of an intronic SNP within DHCR24 was identified and associated with a lower average PiB uptake. Further investigation at whole-brain voxel-wise level indicated that non-carriers of the minor allele had higher PiB uptake in frontal regions compared to carriers. DHCR24 has been previously shown to confer resistance against beta-amyloid and oxidative stress-induced apoptosis, thus our findings support a neuroprotective role. Pathway-based genetic analysis of targeted molecular imaging phenotypes appears promising to help elucidate disease pathophysiology and identify potential therapeutic targets.
Alzheimer’s disease; ADNI; Pathway-based gene analysis; PiB-PET; Endophenotype; Voxel-based analysis
The current study investigated the immediate neurophysiological effects of different types of massage in healthy adults using functional magnetic resonance imaging (fMRI). Much attention has been given to the default mode network, a set of brain regions showing greater activity in the resting state. These regions (i.e. insula, posterior and anterior cingulate, inferior parietal and medial prefrontal cortices) have been postulated to be involved in the neural correlates of consciousness, specifically in arousal and awareness. We posit that massage would modulate these same regions given the benefits and pleasant affective properties of touch. To this end, healthy participants were randomly assigned to one of four conditions: 1. Swedish massage, 2. reflexology, 3. massage with an object or 4. a resting control condition. The right foot was massaged while each participant performed a cognitive association task in the scanner. We found that the Swedish massage treatment activated the subgenual anterior and retrosplenial/posterior cingulate cortices. This increased blood oxygen level dependent (BOLD) signal was maintained only in the former brain region during performance of the cognitive task. Interestingly, the reflexology massage condition selectively affected the retrosplenial/posterior cingulate in the resting state, whereas massage with the object augmented the BOLD response in this region during the cognitive task performance. These findings should have implications for better understanding how alternative treatments might affect resting state neural activity and could ultimately be important for devising new targets in the management of mood disorders.
Electronic supplementary material
The online version of this article (doi:10.1007/s11682-011-9146-z) contains supplementary material, which is available to authorized users.
Touch; Tactile stimulation; fMRI; Default mode network; Interoception; Anterior cingulate; Posterior cingulate; Resting state
How and when the known genetic risk allele, apolipoprotein E-ε4 (APOEε4), confers risk to Alzheimer’s disease has yet to be determined. We studied older adults and found that APOEε4 carriers had greater neural activation in the medial frontal and parahippocampal gyrus during a memory task (cluster-corrected p<.01). When compared to a group of younger adults, interactive effects of age and APOEε4 were found in the inferior frontal—anterior temporal region, one of the first areas to develop amyloid plaques in patients with Alzheimer’s disease, and, in the posterior cingulate, one of the earliest areas to show decreased cerebral metabolism in Alzheimer’s disease. Thus, abnormally high activation in fronto-temporal areas are present in both younger and older APOEε4 carriers confronted with a working memory task when compared to non-APOEε4 carriers. This effect, however, appears to diminish with age.
fMRI; APOE; Alzheimer’s disease; Working memory; Compensation
Cocaine addiction involves an escalation in drug intake which alters many brain functions. The present study documented cocaine-induced changes in brain metabolic activity as a function of cocaine self-administration history. Experimentally naive rhesus monkeys (N=6) were given increasing access to cocaine under a fixed-ratio schedule of i.v. drug self-administration. PET imaging with F-18 labeled fluorodeoxyglucose (FDG) was used to measure acute i.m. cocaine-induced changes in brain metabolism in the cocaine-naïve state, following 60 sessions under limited-access conditions (1hr/day), following 60 sessions under extended-access conditions (4hr/day), and following 4 weeks of drug withdrawal. In the cocaine-naïve state, cocaine-induced increases in brain metabolism were restricted to the prefrontal cortex. As cocaine exposure increased from limited to extended access, metabolic effects expanded throughout the frontal cortex and were induced within the striatum. Conversely, cocaine-induced activation was far less robust following withdrawal. The results highlight a progressive expansion of the metabolic effects of cocaine to include previously unaffected dopamine innervated brain regions as a consequence of cocaine self-administration history. The identification of brain regions progressively influenced by drug exposure may be highly relevant toward efforts to develop treatments for cocaine addiction.
nonhuman primates; cocaine; self-administration; dopamine; fluorodeoxyglucose (FDG); positron emission tomography (PET)
This pilot study aimed to show that information-free stimulation of the tongue can improve behavioral measures and induce sustained neuromodulation of the balance-processing network in individuals with balance dysfunction. Twelve balance-impaired subjects received one week of cranial nerve non-invasive neuromodulation (CN-NINM). Before and after the week of stimulation, postural sway and fMRI activation were measured to monitor susceptibility to optic flow. Nine normal controls also underwent the postural sway and fMRI tests but did not receive CN-NINM. Results showed that before CN-NINM balance-impaired subjects swayed more than normal controls as expected (p≤0.05), and that overall sway and susceptibility to optic flow decreased after CN-NINM (p≤0.005 & p≤0.05). fMRI showed upregulation of visual sensitivity to optic flow in balance-impaired subjects that decreased after CN-NINM. A region of interest analysis indicated that CN-NINM may induce neuromodulation by increasing activity within the dorsal pons (p≤0.01).
fMRI; Optic flow; Neuromodulation; Balance disorders; Brainstem; Plasticity
Acute lymphoblastic leukemia (ALL) is associated with long-term, progressive cognitive deficits and white matter injury. We measured global and regional white and gray matter as well as cognitive function and examined relationships between these variables and cognitive reserve, as indicated by maternal education level, in 28 young survivors of ALL and 31 healthy controls. Results indicated significantly reduced white matter volumes and cognitive testing scores in the ALL group compared to controls. Maternal education was inversely related to both global and regional white matter and directly related to gray matter in ALL and was directly related to both gray and white matter in controls, consistent with the cognitive reserve hypothesis. Cognitive performance was associated with different brain regions in ALL compared to controls. Maternal education was significantly positively correlated with working and verbal memory in ALL as well as processing speed and verbal memory in controls, improving models of cognitive outcome over medical and/or demographic predictors. Our findings suggest that cognitive reserve may be an important factor in brain injury and cognitive outcome in ALL. Additionally, children with ALL may experience some neural reorganization related to cognitive outcome.
Leukemia; Neuroimaging; MRI; Brain volumetrics; Cognitive reserve; Maternal education
Modulation of speech conveys information that is decoded within audio-sensory structures. For example, the termination of an utterance with a rise in pitch distinguishes statements and questions. This study evaluated the sensitivity of early auditory structures to such linguistic prosodic distinctions using mismatch negativity (MMN). MMN is a preattentive auditory event-related potential (ERP) sensitive to stimulus deviance. High-density ERP to pitch contour stimuli were collected in a passive listening oddball paradigm from 11 healthy subjects. Voltage analysis revealed significant MMN responses to declarative and interrogative oddball stimuli. Further, MMN was significantly larger to interrogative, than declarative, deviants, indicating non-symmetric brain processing. These MMNs demonstrate that pitch contour abstractions reflecting interrogative/declarative distinctions can be represented in preattentive auditory sensory memory.
ERP; MMN; Pattern; speech; prosody
Amyloid imaging with [11 C]Pittsburgh Compound-B (PiB) provides in vivo data on plaque deposition in those with, or at risk for, Alzheimer’s disease (AD). We performed a gene-based association analysis of 15 quality-controlled amyloid-pathway associated candidate genes in 103 Alzheimer’s Disease Neuroimaging Initiative participants. The mean normalized PiB uptake value across four brain regions known to have amyloid deposition in AD was used as a quantitative phenotype. The minor allele of an intronic SNP within DHCR24 was identified and associated with a lower average PiB uptake. Further investigation at whole-brain voxel-wise level indicated that non-carriers of the minor allele had higher PiB uptake in frontal regions compared to carriers. DHCR24 has been previously shown to confer resistance against beta-amyloid and oxidative stress-induced apoptosis, thus our findings support a neuroprotective role. Pathway-based genetic analysis of targeted molecular imaging phenotypes appears promising to help elucidate disease pathophysiology and identify potential therapeutic targets.
Alzheimer’s disease; ADNI; Pathway-based gene analysis; PiB-PET; Endophenotype; Voxel-based analysis
The suppression of neural activity in the medial temporal lobe (MTL) has been suggested as a marker of successful recognition of familiarity in healthy subjects, but to be impaired in patients with Alzheimer’s disease (AD). In this study, we investigated whether the ability to suppress MTL activity during repeated exposure to face-name pairs was related to the ability to successfully encode novel associations in 90 individuals ranging from healthy young and older subjects to mildly impaired elderly and AD patients. Activity in the anterior MTL during Repeated stimuli was inversely related to performance in post-scan associative recognition for the Novel face-name pairs. In a subset (n=60) of subjects undergoing more detailed neuropsychological testing, greater MTL Repeated activity was correlated with worse word-list delayed recall performance. Failure of response suppression to familiar information may be a sensitive marker of MTL dysfunction and memory impairment in aging and prodromal AD.
Aging; Alzheimer’s disease; Functional magnetic resonance imaging; Medial temporal lobe; Memory; Repetition suppression