An fNIRS Study of the Effects of Medication on Cognitive Functioning and Cerebral Hemodynamics in Adults with Attention-Deficit/Hyperactivity Disorder

Background: Current research indicates clear distinctions between the general population and individuals diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD), specifically in cognitive processes and physiological brain activity. Stimulant medications have been shown to improve and, in some cases, normalize dysfunction in both these areas. The majority of extant brain imaging literature has included functional magnetic resonance imaging (fMRI) in tandem with neuropsychological tests to explore these relationships. However, functional near-infrared spectroscopy (fNIRS) is a promising neuroimaging technology that offers some unique features including portability, ecological validity, and the ability to detect brain activity via concentrations of oxygenated and deoxygenated blood. Very few studies have used fNIRS as a tool to investigate the impact of medication on adults with ADHD, both in their cognitive functioning and brain hemodynamics. However, there is evidence that this technology may—in addition to providing novel information about cognitive and physiological functioning—actually be better suited to evaluating the ADHD population.Objectives: The present study sought to: 1) compare differences in cognition (using neuropsychological tests) and neurophysiology (using fNIRS) between adults withADHD (when unmedicated) and age-, gender-, and education-matched healthy control(HC) adults, and 2) compare differences in cognition and neurophysiology betweenmedicated and unmedicated states in adults with ADHD. Ultimately, the goal was to investigate the potential application of fNIRS as an assessment tool for both diagnostic(of the physiological underpinnings of the disorder) and monitoring (of the effectiveness of cognition-improving medications) purposes.Participants: Nine individuals aged 18-25 diagnosed with ADHD and nine age-, gender-, and education-matched healthy control participants (HCs).Method: All participants completed two testing sessions. HCs completed both sessions under normal conditions whereas ADHD participants completed one testing session while medicated and the other while unmedicated. Cognitive testing focused on working memory, a domain relevant to ADHD. Testing included 1) a two-subtest WAIS-IV; 2) a Sternberg delayed recognition task (a test of working memory); and 3) a visual n-back task (another working memory test). The latter two tasks were completed while participants were connected to a continuous wave fNIRS system to record cerebral hemodynamic activity during working memory performance. Demographic variables, confirmation of diagnosistic status, medications, and recent daily activities regarding caffeine, alcohol, tobacco, and other behaviors that could impact fNIRS data were recorded.Results: Cognitively, while healthy controls performed better on working memory tasks than ADHD participants, and ADHD participants generally performed better when medicated than unmedicated, neither comparison reached significance. Physiologically, there were no significant differences in PFC activation between the HC and ADHD groups, nor between medicated and unmedicated states within the ADHD group.Conclusions: The findings of this study mirror previous findings of the cognitive effects of medication in ADHD. Not surprisingly, individuals with ADHD performed working memory tasks less accurately and more slowly than controls and the intake of stimulant medication led to an improvement in performance that reached levels similar to healthy individuals. By contrast, the medication-induced working memory improvements among adults with ADHD were not reflected in corresponding physiological changes measured by fNIRS. The lack of significant findings in this study may be due to low statistical power, though alternative explanations are also explored. Nonetheless, before fNIRS can contribute to clinical diagnosis and treatment of ADHD, more research is needed to establish its clinical application.M.S., Psychology -- Drexel University, 201

Brain tissue- and region-specific abnormalities on volumetric MRI scans in 21 patients with Bardet-Biedl syndrome (BBS)

Abstract Background Bardet-Biedl syndrome (BBS) is a heterogeneous human disorder inherited in an autosomal recessive pattern, and characterized by the primary findings of obesity, polydactyly, hypogonadism, and learning and behavioural problems. BBS mouse models have a neuroanatomical phenotype consisting of third and lateral ventriculomegaly, thinning of the cerebral cortex, and reduction in the size of the corpus striatum and hippocampus. These abnormalities raise the question of whether humans with BBS have a characteristic morphologic brain phenotype. Further, although behavioral, developmental, neurological and motor defects have been noted in patients with BBS, to date, there are limited reports of brain findings in BBS. The present study represents the largest systematic evaluation for the presence of structural brain malformations and/or progressive changes, which may contribute to these functional problems. Methods A case-control study of 21 patients, most aged 13-35 years, except for 2 patients aged 4 and 8 years, who were diagnosed with BBS by clinical criteria and genetic analysis of known BBS genes, and were evaluated by qualitative and volumetric brain MRI scans. Healthy controls were matched 3:1 by age, sex and race. Statistical analysis was performed using SAS language with SAS STAT procedures. Results All 21 patients with BBS were found to have statistically significant region- and tissue-specific patterns of brain abnormalities. There was 1) normal intracranial volume; 2) reduced white matter in all regions of the brain, but most in the occipital region; 3) preserved gray matter volume, with increased cerebral cortex volume in only the occipital lobe; 4) reduced gray matter in the subcortical regions of the brain, including the caudate, putamen and thalamus, but not in the cerebellum; and 5) increased cerebrospinal fluid volume. Conclusions There are distinct and characteristic abnormalities in tissue- and region- specific volumes of the brain in patients with BBS, which parallel the findings, described in BBS mutant mouse models. Some of these brain abnormalities may be progressive and associated with the reported neurological and behavioral problems. Further future correlation of these MRI scan findings with detailed neurologic and neuropsychological exams together with genotype data will provide better understanding of the pathophysiology of BBS.</p

Distinct cortical responses to 2D figures defined by motion contrast

AbstractMotion contrast contributes to the segregation of a two-dimensional figure from its background, yet many questions remain about its neural mechanisms. We measured steady-state visual evoked potential (SSVEP) responses to moving dot displays in which figure regions emerged from and disappeared into the background at a specific temporal frequency (1.2Hz, F1), based on regional differences of dot direction and global direction coherence. The goal was to measure the cortical response function across a range of motion contrast magnitudes. In two experiments using both a low channel count electrode array (Experiment 1) and a high density array (Experiment 2), we observed two distinct phase-locked evoked responses that were similar across motion contrast type. A response at 1.2Hz (1F1) increased in amplitude with increasing magnitudes of direction or coherence contrast. A response at 2.4Hz (2F1) increased in amplitude, but saturated at low levels of direction or coherence contrast. The two components showed different scalp distributions – the 1F1 was strongest along medial occipital channels, while the 2F1 was bilaterally distributed. Taken together, the studies suggest that figures defined by different types of motion contrast are processed by cortical systems with similar dynamics, and that there are separable neural systems devoted to (i) signaling the absolute magnitude of motion contrast and (ii) detecting when a figure defined by motion contrast appears and disappears from view