Cognitive Complaints in Motor Functional Neurological (Conversion) Disorders: A Focused Review and Clinical Perspective.

Functional neurological (conversion) disorder (FND) is a neuropsychiatric condition characterized by sensorimotor symptoms exhibiting features incompatible with other neurologic diseases. Individuals with motor FND (mFND) typically present with limb weakness, nonepileptic seizures, and/or abnormal movements. However, this population also frequently reports clouded thinking, inattention, and memory difficulties. Cognitive complaints in individuals with mFND are important to evaluate as they may negatively impact quality of life and impede treatment engagement. We provide a narrative review of the neuropsychological testing literature detailing neurocognitive profiles of individuals with mFND. We also present three illustrative clinical cases at the intersection of mFND and cognitive concerns. Several studies and our case examples highlight that generally normal cognitive performance can be observed concurrently with subjective cognitive complaints in some individuals with mFND; this mismatch may be a possible "rule-in" sign of functional cognitive symptoms. Other studies have reported impairments in attention, memory, language, visuospatial, and executive functioning in individuals with mFND. These impairments could be related to medical-psychiatric comorbidities, psychotropic medication side effects, and intrinsic disease mechanisms. When evaluating individuals with mFND and their cognitive complaints, clinicians can use performance validity test and psychopathology findings to help them interpret the neuropsychological test results. Perceptual mismatches between intact objective cognitive performance and subjective cognitive complaints may reflect a negative attentional bias for cognitive abilities that can be targeted with cognitive retraining and cognitive behavioral therapy. Neuropsychological evaluations may provide a useful adjunctive tool clinicians can use to help assess individuals with mFND and cognitive concerns.

Resting-State Functional MR Imaging for Determining Language Laterality in Intractable Epilepsy.

Purpose To measure the accuracy of resting-state functional magnetic resonance (MR) imaging in determining hemispheric language dominance in patients with medically intractable focal epilepsies against the results of an intracarotid amobarbital procedure (IAP). Materials and Methods This study was approved by the institutional review board, and all subjects gave signed informed consent. Data in 23 patients with medically intractable focal epilepsy were retrospectively analyzed. All 23 patients were candidates for epilepsy surgery and underwent both IAP and resting-state functional MR imaging as part of presurgical evaluation. Language dominance was determined from functional MR imaging data by calculating a laterality index (LI) after using independent component analysis. The accuracy of this method was assessed against that of IAP by using a variety of thresholds. Sensitivity and specificity were calculated by using leave-one-out cross validation. Spatial maps of language components were qualitatively compared among each hemispheric language dominance group. Results Measurement of hemispheric language dominance with resting-state functional MR imaging was highly concordant with IAP results, with up to 96% (22 of 23) accuracy, 96% (22 of 23) sensitivity, and 96% (22 of 23) specificity. Composite language component maps in patients with typical language laterality consistently included classic language areas such as the inferior frontal gyrus, the posterior superior temporal gyrus, and the inferior parietal lobule, while those of patients with atypical language laterality also included non-classical language areas such as the superior and middle frontal gyri, the insula, and the occipital cortex. Conclusion Resting-state functional MR imaging can be used to measure language laterality in patients with medically intractable focal epilepsy. (©) RSNA, 2016 Online supplemental material is available for this article.

Decoding information about cognitive health from the brainwaves of sleep.

Sleep electroencephalogram (EEG) signals likely encode brain health information that may identify individuals at high risk for age-related brain diseases. Here, we evaluate the correlation of a previously proposed brain age biomarker, the "brain age index" (BAI), with cognitive test scores and use machine learning to develop and validate a series of new sleep EEG-based indices, termed "sleep cognitive indices" (SCIs), that are directly optimized to correlate with specific cognitive scores. Three overarching cognitive processes were examined: total, fluid (a measure of cognitive processes involved in reasoning-based problem solving and susceptible to aging and neuropathology), and crystallized cognition (a measure of cognitive processes involved in applying acquired knowledge toward problem-solving). We show that SCI decoded information about total cognition (Pearson's r = 0.37) and fluid cognition (Pearson's r = 0.56), while BAI correlated only with crystallized cognition (Pearson's r = - 0.25). Overall, these sleep EEG-derived biomarkers may provide accessible and clinically meaningful indicators of neurocognitive health.

Neuropsychiatric symptoms in a occipito-temporal infarction with remarkable long-term functional recovery.

Posterior circulation infarctions (PCI) constitute 5-25% of ischemic strokes. PCI of the occipital lobe present with a panoply of symptoms including quadrantanopsia, topographical disorientation, and executive dysfunction. Long-term cognitive recovery after PCI is not well described. However, the adult brain is remarkably plastic, capable of adapting and remodeling. We describe a 43-year-old right-handed woman who complained of black spots in both eyes, headaches, photophobia, and a feeling she would faint. Initial neurological exam and a CT scan were normal; she was diagnosed with ocular migraine. A second neurological exam a week later showed left superior quadrantopsia; an MRI scan suggested right occipito-temporal infarct. In subsequent months, the patient complained of fatigue, quadrantanopsia, memory problems, and topographical disorientation. The patient participated in multi-modality treatment, and in self-directed arts projects and physical activities. Six years later, she reported noticeable improvements in cognition and daily functioning, which were documented on neurocognitive testing. Comparison between initial and subsequent MRIs using FreeSurfer 5.3 identified neuroplastic brain changes in areas serving similar functions to the areas injured from the stroke. The case illustrates the neuropsychiatric presentation after right occipito-temporal stroke, the value of formal and self-directed cognitive rehabilitation, the extended time to cognitive recovery, and the ability of the brain to undergo neuroplastic changes.

Does hippocampal FDG-PET asymmetry predict verbal memory dysfunction after left temporal lobectomy?

The primary aim of this study was to determine whether hippocampal asymmetries in fluorodeoxyglucose (FDG) uptake on preoperative PET scans would predict post-temporal lobectomy verbal memory (VM) decline in patients with left temporal lobe epilepsy. A quantitative asymmetry index (AI) of uptake values within a hippocampal region of interest (ROI) was defined by an automated technique. No statistically significant effect of the hippocampal AI on the outcome measure, the pre- to postsurgical change in Logical Memory Percent Retention, was evident. Post hoc analyses revealed that AIs of the superior and inferior temporal gyri approached significance, however, with relatively greater left-sided preoperative metabolism predicting better VM outcomes. This finding suggests reorganization of function and/or retained function of remaining tissue. Although hippocampal FDG-PET asymmetries did not significantly predict changes in VM, the predictive value of neocortical AIs should be further explored. Automated ROI parcellation provides a feasible tool for use in such investigations.

Medial temporal lobe activity for recognition of recent and remote famous names: an event-related fMRI study.

Previous neuroimaging studies examining recognition of famous faces have identified activation of an extensive bilateral neural network [Gorno Tempini, M. L., Price, C. J., Josephs, O., Vandenberghe, R., Cappa, S. F., Kapur, N. et al. (1998). The neural systems sustaining face and proper-name processing. Brain, 121, 2103-2118], including the medial temporal lobe (MTL) and specifically the hippocampal complex [Haist, F., Bowden, G. J., & Mao, H. (2001). Consolidation of human memory over decades revealed by functional magnetic resonance imaging. Nature Neuroscience, 4, 1139-1145; Leveroni, C. L., Seidenberg, M., Mayer, A. R., Mead, L. A., Binder, J. R., & Rao, S. M. (2000). Neural systems underlying the recognition of familiar and newly learned faces. Journal of Neuroscience, 20, 878-886]. One model of hippocampal functioning in autobiographical, episodic memory retrieval argues that the hippocampal complex remains active in retrieval tasks regardless of time or age of memory (multiple trace theory, MTT), whereas another proposal posits that the hippocampal complex plays a time-limited role in retrieval of autobiographical memories. The current event-related fMRI study focused on the medial temporal lobe and its response to recognition judgments of famous names from two distinct time epochs (1990s and 1950s) in 15 right-handed healthy older adults (mean age=70 years). A pilot study with an independent sample of young and older subjects ensured that the stimuli were representative of a recent and remote time period. Increased MR signal activity was observed on a bilateral basis for both the hippocampus and parahippocampal gyrus (PHG) during recognition of familiar names from both the recent and remote time periods when compared to non-famous names. However, the impulse response functions in the right hippocampus and right PHG demonstrated a differential response to stimuli from different time epochs, with the 1990s names showing the greatest MR signal intensity change, followed by the 1950s names, followed by foils. The finding that recognition of famous names produced significant bilateral MTL activation regardless of time epoch relative to foils provides support for the MTT model. However, the finding of a temporal gradient in the right MTL also provides support for the HC model, given the greater MTL response associated with recently famous names relative to remotely famous names.

Intra-stimulation discharges: an overlooked cortical electrographic entity triggered by direct electrical stimulation.

OBJECTIVE: Intra-stimulation discharges (IDs) can occur during language mapping, are largely unrecognized, and may precede the occurrence of after-discharges (ADs) and seizures. This study aimed to identify predictors of ID occurrence and determine whether IDs increase the probability of triggered ADs. METHODS: A total of 332 stimulation events performed during language mapping were analyzed in 3 patients who underwent intracranial EEG recordings during evaluations for epilepsy surgery. IDs were identified in 76 stimulation events. The relationships between IDs and the stimulus current intensity, stimulation duration, and proximity to regions of abnormal cortical excitability [characterized by the presence of baseline epileptiform discharges (BEDs)] were determined using regression analysis. RESULTS: The presence of BEDs in close proximity to stimulation, an increase in stimulus intensity by 1 mA, and an increase in stimulation duration by 1s independently increased the odds of triggering IDs by 7.40, 1.37, and 1.39 times, respectively. All IDs were triggered during stimulations in the temporal lobe. The occurrence of IDs increased the odds of triggering ADs 5-fold. CONCLUSIONS: Longer stimulations, higher currents, and the presence of BEDs at the stimulation site increase the probability of ID occurrence, which in turn increases the probability of triggering ADs. SIGNIFICANCE: Attention to IDs may improve the safety and precision of neurophysiologic mapping.

Loss of resting-state posterior cingulate flexibility is associated with memory disturbance in left temporal lobe epilepsy.

The association between cognition and resting-state fMRI (rs-fMRI) has been the focus of many recent studies, most of which use stationary connectivity. The dynamics or flexibility of connectivity, however, may be seminal for understanding cognitive functioning. In temporal lobe epilepsy (TLE), stationary connectomic correlates of impaired memory have been reported mainly for the hippocampus and posterior cingulate cortex (PCC). We therefore investigate resting-state and task-based hippocampal and PCC flexibility in addition to stationary connectivity in left TLE (LTLE) patients. Sixteen LTLE patients were analyzed with respect to rs-fMRI and task-based fMRI (t-fMRI), and underwent clinical neuropsychological testing. Flexibility of connectivity was calculated using a sliding-window approach by determining the standard deviation of Fisher-transformed Pearson correlation coefficients over all windows. Stationary connectivity was also calculated. Disturbed memory was operationalized as having at least one memory subtest score equal to or below the 5th percentile compared to normative data. Lower PCC flexibility, particularly in the contralateral (i.e. right) hemisphere, was found in memory-disturbed LTLE patients, who had up to 22% less flexible connectivity. No significant group differences were found with respect to hippocampal flexibility, stationary connectivity during both rs-fMRI and t-fMRI, or flexibility during t-fMRI. Contralateral resting-state PCC flexibility was able to classify all but one patient with respect to their memory status (94% accuracy). Flexibility of the PCC during rest relates to memory functioning in LTLE patients. Loss of flexible connectivity to the rest of the brain originating from the PCC, particularly contralateral to the seizure focus, is able to discern memory disturbed patients from their preserved counterparts. This study indicates that the dynamics of resting-state connectivity are associated with cognitive status of LTLE patients, rather than stationary connectivity.

fMRI biomarker of early neuronal dysfunction in presymptomatic Huntington's Disease.

BACKGROUND AND PURPOSE: Functional MR imaging (fMRI) has been used to probe basal ganglia function in people with presymptomatic Huntington's disease (pre-HD). A previous fMRI study in healthy individuals demonstrated activation of the basal ganglia during a time-discrimination task. The current study was designed to examine the relative sensitivity of fMRI compared with that of behavioral testing and morphometric measurements in detecting early neurodegenerative changes related to Huntington's disease (HD). METHODS: Pre-HD participants were assigned to two groups based on estimated years to diagnosis of manifest disease: close <12 years and far >or=12 years. Age at disease onset was estimated using a regression equation based on the number of trinucleotide CAG repeats. The time-discrimination task required participants to determine whether a specified interval was shorter or longer than a standard interval of 1200 milliseconds. RESULTS: Participants in the close group performed more poorly on the time-task discrimination than did control subjects; however, no differences were observed between far participants and control subjects. Similarly, close participants had reduced bilateral caudate volume relative to that of control subjects, whereas far participants did not. On functional imaging, close participants had significantly less activation in subcortical regions (caudate, thalamus) than control subjects; far participants had an intermediate degree of activation. In contrast, far participants had hyperactivation in medial hemispheric structures (anterior cingulate, pre-supplementary motor area) relative to close and control subjects. CONCLUSION: Hyperactivation of medial prefrontal regions compensated for reduced subcortical participation during time discrimination in pre-HD. This pattern of brain activation may represent an early neurobiologic marker of neuronal dysfunction.

The impact of neuropsychological functioning on adherence to HAART in HIV-infected substance abuse patients.

This study assessed the frequency of neuropsychological impairment and its relationship to adherence in a sample of HIV-infected injection drug users (IDUs) in treatment. One hundred eight participants recruited between September 2006 and October 2008 completed psychodiagnostic and neuropsychological assessments and monitored HAART adherence over a 2-week period via the use of Medication Event Monitoring System (MEMS) electronic pill caps and self-report. Assessment of concurrent functioning included clinician-rated scales of depression and substance use severity, and a battery of neuropsychological tests. Findings from individual neuropsychological tests were converted to Z scores relative to standard norms and averaged to form a composite score (NPZ). NPZ was generally poor (mean = -1.505, standard deviation = 1.120), with 76.9% of the sample being classified as highly impaired. Self-reported adherence was significantly higher than MEMS cap adherence. In contrast with previous studies, overall neuropsychological functioning was not a significant predictor of electronically monitored or self-reported adherence. However, examiner-rated current global severity of substance use and delayed word list recall emerged as significant predictors of self-reported adherence. Additionally, estimated premorbid verbal intelligence emerged as a significant predictor of the discrepancy between electronically monitored and self-reported adherence. Given the extent of neuropsychological impairment in this sample, future studies should examine the degree to which the impact of neuropsychological impairment may moderate interventions for this population, and the extent to which skills to cope with neuropsychological problems may boost the potential efficacy of such interventions.

Testing neuropsychological hypotheses for cognitive deficits in psychopathic criminals: a study of global-local processing.

Competing hypotheses about neuropsychological mechanisms underlying psychopathy are seldom examined in the same study. We tested the left hemisphere activation hypothesis and the response modulation hypothesis of psychopathy in 172 inmates completing a global-local processing task under local bias, global bias, and neutral conditions. Consistent with the left hemisphere activation hypothesis, planned comparisons showed that psychopathic inmates classified local targets more slowly than nonpsychopathic inmates in a local bias condition and exhibited a trend toward similar deficits for global targets in this condition. However, contrary to the response modulation hypothesis, psychopaths were no slower to respond to local targets in a global bias condition. Because psychopathic inmates were not generally slower to respond to local targets, results are also not consistent with a general left hemisphere dysfunction account. Correlational analyses also indicated deficits specific to conditions presenting most targets at the local level initially. Implications for neuropsychological conceptualizations of psychopathy are considered.