Do Epilepsy Patients with Cognitive Impairment Have Alzheimer's Disease-like Brain Metabolism?

Although not classically considered together, there is emerging evidence that Alzheimer's disease (AD) and epilepsy share a number of features and that each disease predisposes patients to developing the other. Using machine learning, we have previously developed an automated fluorodeoxyglucose positron emission tomography (FDG-PET) reading program (i.e., MAD), and demonstrated good sensitivity (84%) and specificity (95%) for differentiating AD patients versus healthy controls. In this retrospective chart review study, we investigated if epilepsy patients with/without mild cognitive symptoms also show AD-like metabolic patterns determined by the MAD algorithm. Scans from a total of 20 patients with epilepsy were included in this study. Because AD diagnoses are made late in life, only patients aged ≥40 years were considered. For the cognitively impaired patients, four of six were identified as MAD+ (i.e., the FDG-PET image is classified as AD-like by the MAD algorithm), while none of the five cognitively normal patients was identified as MAD+ (χ2 = 8.148, p = 0.017). These results potentially suggest the usability of FDG-PET in prognosticating later dementia development in non-demented epilepsy patients, especially when combined with machine learning algorithms. A longitudinal follow-up study is warranted to assess the effectiveness of this approach.

Tingles down the spinal cord: A spinal functional magnetic resonance imaging investigation of the autonomous sensory meridian response.

Autonomous sensory meridian response (ASMR) is a perceptual and emotional phenomenon in which specific sensory stimuli elicit a feeling of calm as well as tingling sensations on the scalp, neck, and shoulders. In the current study, we use fMRI to examine whether the motoric and sensory regions of the spinal cord segments associated with these body parts show increased activity during ASMR experiences. Nine individuals with ASMR completed six spinal functional magnetic resonance imaging runs while passively viewing videos. Three of the videos were shown (through pre-testing) to elicit ASMR tingles and three videos did not (i.e., control videos). The results demonstrated that ASMR-related stimuli elicited activity in dorsal (sensory) regions of spinal cord segments C1, C5, and C6; activity was observed in ventral (motoric) regions of segments C2-C8. Similar activity was not detected in response to control videos.

Alzheimer's Disease-Related Metabolic Pattern in Diverse Forms of Neurodegenerative Diseases.

Dementia is broadly characterized by cognitive and psychological dysfunction that significantly impairs daily functioning. Dementia has many causes including Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration (FTLD). Detection and differential diagnosis in the early stages of dementia remains challenging. Fueled by AD Neuroimaging Initiatives (ADNI) (Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. As such, the investigators within ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report.), a number of neuroimaging biomarkers for AD have been proposed, yet it remains to be seen whether these markers are also sensitive to other types of dementia. We assessed AD-related metabolic patterns in 27 patients with diverse forms of dementia (five had probable/possible AD while others had atypical cases) and 20 non-demented individuals. All participants had positron emission tomography (PET) scans on file. We used a pre-trained machine learning-based AD designation (MAD) framework to investigate the AD-related metabolic pattern among the participants under study. The MAD algorithm showed a sensitivity of 0.67 and specificity of 0.90 for distinguishing dementia patients from non-dementia participants. A total of 18/27 dementia patients and 2/20 non-dementia patients were identified as having AD-like patterns of metabolism. These results highlight that many underlying causes of dementia have similar hypometabolic pattern as AD and this similarity is an interesting avenue for future research.

Computerized Dual-Task Testing of Gait Visuomotor and Cognitive Functions in Parkinson's Disease: Test-Retest Reliability and Validity.

BACKGROUND: Mobility and cognitive impairments in Parkinson's disease (PD) often coexist and are prognostic of adverse health events. Consequently, assessment and training that simultaneously address both gait function and cognition are important to consider in rehabilitation and promotion of healthy aging. For this purpose, a computer game-based rehabilitation treadmill platform (GRP) was developed for dual-task (DT) assessment and training. OBJECTIVE: The first objective was to establish the test-retest reliability of the GRP assessment protocol for DT gait, visuomotor and executive cognitive function in PD patients. The second objective was to examine the effect of task condition [single task (ST) vs. DT] and disease severity (stage 2 vs. stage 3) on gait, visuomotor and cognitive function. METHODS: Thirty individuals aged 55 to 70 years, diagnosed with PD; 15 each at Hoehn and Yahr scale stage 2 (PD-2) and 3 (PD-3) performed a series of computerized visuomotor and cognitive game tasks while sitting (ST) and during treadmill walking (DT). A treadmill instrumented with a pressure mat was used to record center of foot pressure and compute the average and coefficient of variation (COV) of step time, step length, and drift during 1-min, speed-controlled intervals. Visuomotor and cognitive game performance measures were quantified using custom software. Testing was conducted on two occasions, 1 week apart. RESULTS: With few exceptions, the assessment protocol showed moderate to high intraclass correlation coefficient (ICC) values under both ST and DT conditions for the spatio-temporal gait measures (average and COV), as well as the visuomotor tracking and cognitive game performance measures. A significant decline in gait, visuomotor, and cognitive game performance measures was observed during DT compared to ST conditions, and in the PD-3 compared to PD-2 groups. CONCLUSION: The high to moderate ICC values along with the lack of systematic errors in the measures indicate that this tool has the ability to repeatedly record reliable DT interference (DTI) effects over time. The use of interactive digital media provides a flexible method to produce and evaluate DTI for a wide range of executive cognitive activities. This also proves to be a sensitive tool for tracking disease progression. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT03232996.

Changes in Metabolic Activity and Gait Function by Dual-Task Cognitive Game-Based Treadmill System in Parkinson's Disease: Protocol of a Randomized Controlled Trial.

Balance and gait impairments, and consequently, mobility restrictions and falls are common in Parkinson's disease (PD). Various cognitive deficits are also common in PD and are associated with increased fall risk. These mobility and cognitive deficits are limiting factors in a person's health, ability to perform activities of daily living, and overall quality of life. Community ambulation involves many dual-task (DT) conditions that require processing of several cognitive tasks while managing or reacting to sudden or unexpected balance challenges. DT training programs that can simultaneously target balance, gait, visuomotor, and cognitive functions are important to consider in rehabilitation and promotion of healthy active lives. In the proposed multi-center, randomized controlled trial (RCT), novel behavioral positron emission tomography (PET) brain imaging methods are used to evaluate the molecular basis and neural underpinnings of: (a) the decline of mobility function in PD, specifically, balance, gait, visuomotor, and cognitive function, and (b) the effects of an engaging, game-based DT treadmill walking program on mobility and cognitive functions. Both the interactive cognitive game tasks and treadmill walking require continuous visual attention, and share spatial processing functions, notably to minimize any balance disturbance or gait deviation/stumble. The ability to "walk and talk" normally includes activation of specific regions of the prefrontal cortex (PFC) and the basal ganglia (site of degeneration in PD). The PET imaging analysis and comparison with healthy age-matched controls will allow us to identify areas of abnormal, reduced activity levels, as well as areas of excessive activity (increased attentional resources) during DT-walking. We will then be able to identify areas of brain plasticity associated with improvements in mobility functions (balance, gait, and cognition) after intervention. We expect the gait-cognitive training effect to involve re-organization of PFC activity among other, yet to be identified brain regions. The DT mobility-training platform and behavioral PET brain imaging methods are directly applicable to other diseases that affect gait and cognition, e.g., cognitive vascular impairment, Alzheimer's disease, as well as in aging.

Systematic review and meta-analyses of neural structural and functional differences in generalized anxiety disorder and healthy controls using magnetic resonance imaging.

OBJECTIVE: To compare structure, functional connectivity (FC) and task-based neural differences in subjects with generalized anxiety disorder (GAD) compared to healthy controls (HC). METHODS: The Embase, Ovid Medline, PsycINFO, Scopus, and Web of Science databases were searched from inception until March 12, 2018. Two reviewers independently screened titles, abstracts, and full-text articles. Data were extracted from records directly contrasting GAD and HC that included structure (connectivity and local indices such as volume, etc.), FC, or task-based magnetic resonance imaging data. Meta-analyses were conducted, as applicable, using AES-SDM software. RESULTS: The literature search produced 4,645 total records, of which 85 met the inclusion criteria for the systematic review. Records included structural (n = 35), FC (n = 33), and task-based (n = 42) findings. Meta-analyses were conducted on voxel-based morphometry and task-based results. DISCUSSION: The systematic review confirms and extends findings from previous reviews. Although few whole-brain resting state studies were conducted, key nodes of resting state networks have altered physiology: the hippocampus (default network), ACC and amygdala (salience network), have reduced volume, and the dlPFC (central executive network) and ACC have reduced FC with the amygdala in GAD. Nodes in the sensorimotor network are also altered with greater pre- and postcentral volume, reduced supplementary motor area volume, and reduced FC in anterior and increased FC in posterior cerebellum. CONCLUSIONS: Despite limitations due to sample size, the meta-analyses highly agree with the systematic review and provide evidence of widely distributed neural differences in subjects with GAD, compared to HC. Further research optimized for meta-analyses would greatly improve large-scale comparisons.

Lateralized Brainstem and Cervical Spinal Cord Responses to Aversive Sounds: A Spinal fMRI Study.

Previous research has delineated the networks of brain structures involved in the perception of emotional auditory stimuli. These include the amygdala, insula, and auditory cortices, as well as frontal-lobe, basal ganglia, and cerebellar structures involved in the planning and execution of motoric behaviors. The aim of the current research was to examine whether emotional sounds also influence activity in the brainstem and cervical spinal cord. Seventeen undergraduate participants completed a spinal functional magnetic resonance imaging (fMRI) study consisting of two fMRI runs. One run consisted of three one-minute blocks of aversive sounds taken from the International Affective Digitized Sounds (IADS) stimulus set; these blocks were interleaved by 40-s rest periods. The other block consisted of emotionally neutral stimuli also drawn from the IADS. The results indicated a stark pattern of lateralization. Aversive sounds elicited greater activity than neutral sounds in the right midbrain and brainstem, and in right dorsal and ventral regions of the cervical spinal cord. Neutral stimuli, on the other hand, elicited less neural activity than aversive sounds overall; these responses were left lateralized and were found in the medial midbrain and the dorsal sensory regions of the cervical spinal cord. Together, these results demonstrate that aversive auditory stimuli elicit increased sensorimotor responses in brainstem and cervical spinal cord structures.

Neural Responses to Consciously and Unconsciously Perceived Emotional Faces: A Spinal fMRI Study.

Emotional stimuli modulate activity in brain areas related to attention, perception, and movement. Similar increases in neural activity have been detected in the spinal cord, suggesting that this understudied component of the central nervous system is an important part of our emotional responses. To date, previous studies of emotion-dependent spinal cord activity have utilized long presentations of complex emotional scenes. The current study differs from this research by (1) examining whether emotional faces will lead to enhanced spinal cord activity and (2) testing whether these stimuli require conscious perception to influence neural responses. Fifteen healthy undergraduate participants completed six spinal functional magnetic resonance imaging (fMRI) runs in which three one-minute blocks of fearful, angry, or neutral faces were interleaved with 40-s rest periods. In half of the runs, the faces were clearly visible while in the other half, the faces were displayed for only 17 ms. Spinal fMRI consisted of half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequences targeting the cervical spinal cord. The results indicated that consciously perceived faces expressing anger elicited significantly more activity than fearful or neutral faces in ventral (motoric) regions of the cervical spinal cord. When stimuli were presented below the threshold of conscious awareness, neutral faces elicited significantly more activity than angry or fearful faces. Together, these data suggest that the emotional modulation of spinal cord activity is most impactful when the stimuli are consciously perceived and imply a potential threat toward the observer.

Trait Emotional Empathy and Resting State Functional Connectivity in Default Mode, Salience, and Central Executive Networks.

Emotional empathy is the ability to experience and/or share another person’s emotional states and responses. Although some research has examined the neural correlates of emotional empathy, there has been little research investigating whether this component of empathy is related to the functional connectivity of resting state networks in the brain. In the current study, 32 participants answered a trait emotional empathy questionnaire in a session previous to their functional magnetic resonance imaging scan. Results indicate that emotional empathy scores were correlated with different patterns of functional connectivity in the default mode network (DMN), salience network (SN), and left and right central executive networks. For example, within the DMN, emotional empathy scores positively correlated with connectivity in the premotor cortex. Within the SN, empathy scores were positively correlated with the fusiform gyrus and cuneus. These findings demonstrate that emotional empathy is associated with unique patterns of functional connectivity in four of the brain’s resting state networks.

Salience, central executive, and sensorimotor network functional connectivity alterations in failed back surgery syndrome.

OBJECTIVE: This study examined the altered patterns of functional connectivity in task-positive resting state networks in failed back surgery syndrome (FBSS) patients compared to healthy controls using functional magnetic resonance imaging (fMRI). This work stems from a previous study in which alterations in the task-negative default mode network were investigated. DESIGN: Participants underwent a 7-minute resting state fMRI scan in which they lay still, with eyes closed, in the absence of a task. SETTING: Scanning took place at the National Research Council's 3Tesla MRI magnet in Winnipeg, Canada. SUBJECTS: Fourteen patients with FBSS and age- and gender-matched controls participated in this study. Three patients were removed from the analyses due to image artefact (n=1) and effective pain treatment (n=2). Eleven patients (5 female, mean age 52.7 years) and their matched controls were included in the final analyses. METHODS: Resting state fMRI data were analyzed using an independent component analysis, yielding three resting state networks of interest: the salience network (SN), involved in detection of external stimuli, central executive network (CEN), involved in cognitions, and sensorimotor network (SeN), involved in sensory and motor integration. Analysis of Variance contrasts were performed for each network, comparing functional connectivity differences between FBSS patients and healthy controls. RESULTS: Alterations were observed in all three resting state networks, primarily relating to pain and its processing in the FBSS group. Specifically, compared to healthy controls, FBSS patients demonstrated increased functional connectivity in the anterior cingulate cortex within the SN, medial frontal gyrus in the CEN, and precentral gyrus within the SeN. FBSS patients also demonstrated decreased functional connectivity in the medial frontal gyrus in the SeN compared to healthy controls. Interestingly, we also observed internetwork functional connectivity in the SN and SeN. CONCLUSIONS: FBSS is associated with altered patterns of functional connectivity in the SN, CEN, and SeN. Taken together with our previous work, this reveals that a chronic pain condition can have a dramatic effect on the connectivity of multiple resting state networks. IMPLICATIONS: These data suggest that a chronic pain condition-FBSS-is associated with disruptions to networks of functional connectivity in brain areas that are involved in numerous functions, including pain processing, sensation, and movement. It is possible that the alterations in these networks may contribute to other common chronic pain comorbidities, such as disrupted cognitions or anxiety. Previous research shows that during experimentally-induced pain, these networks can return to initial levels of functioning, indicating that these functional alterations are likely not permanent.

Separating neural activity associated with emotion and implied motion: An fMRI study.

Previous research provides evidence for an emo-motoric neural network allowing emotion to modulate activity in regions of the nervous system related to movement. However, recent research suggests that these results may be due to the movement depicted in the stimuli. The purpose of the current study was to differentiate the unique neural activity of emotion and implied motion using functional MRI. Thirteen healthy participants viewed 4 sets of images: (a) negative stimuli implying movement, (b) negative stimuli not implying movement, (c) neutral stimuli implying movement, and (d) neutral stimuli not implying movement. A main effect for implied motion was found, primarily in regions associated with multimodal integration (bilateral insula and cingulate), and visual areas that process motion (bilateral middle temporal gyrus). A main effect for emotion was found primarily in occipital and parietal regions, indicating that emotion enhances visual perception. Surprisingly, emotion also activated the left precentral gyrus, a motor region. These results demonstrate that emotion elicits activity above and beyond that evoked by the perception of implied movement, but that the neural representations of these characteristics overlap. (PsycINFO Database Record

Altered Neural Activity Associated with Mindfulness during Nociception: A Systematic Review of Functional MRI.

OBJECTIVE: To assess the neural activity associated with mindfulness-based alterations of pain perception. METHODS: The Cochrane Central, EMBASE, Ovid Medline, PsycINFO, Scopus, and Web of Science databases were searched on 2 February 2016. Titles, abstracts, and full-text articles were independently screened by two reviewers. Data were independently extracted from records that included topics of functional neuroimaging, pain, and mindfulness interventions. RESULTS: The literature search produced 946 total records, of which five met the inclusion criteria. Records reported pain in terms of anticipation (n = 2), unpleasantness (n = 5), and intensity (n = 5), and how mindfulness conditions altered the neural activity during noxious stimulation accordingly. CONCLUSIONS: Although the studies were inconsistent in relating pain components to neural activity, in general, mindfulness was able to reduce pain anticipation and unpleasantness ratings, as well as alter the corresponding neural activity. The major neural underpinnings of mindfulness-based pain reduction consisted of altered activity in the anterior cingulate cortex, insula, and dorsolateral prefrontal cortex.

Assessing Nociception by fMRI of the Human Spinal Cord: A Systematic Review.

OBJECTIVE: To assess the use of fMRI of the spinal cord in measuring noxious stimulation. METHODS: The Scopus, Medline, EMBASE, and Web of Science databases were searched, along with the reference lists of included articles. Two independent reviewers screened abstracts, full-text articles, and extracted data. Original research was included if fMRI of the human spinal cord was used to measure responses to noxious stimulation. RESULTS: Of the 192 abstracts screened, 19 met the search criteria and were divided according to their focus: investigating pain responses (n = 6), methodology (n = 6), spinal cord injury (n = 2), or cognition-pain interactions (n = 5). All but one study appear to have observed activity in ipsilateral and dorsal gray matter regions in response to noxious stimuli, although contralateral or ventral activity was also widely observed. CONCLUSIONS: Although nociception can be investigated using spinal fMRI, establishing reliability, standardizing methodology, and reporting of results will greatly advance this field.