Douglas L. Chute

Functional Near Infrared Spectroscopy (fNIRS): An Emerging Neuroimaging Technology with Important Applications for the Study of Brain Disorders

Functional near-infrared spectroscopy (fNIRS) is an emerging functional neuroimaging technology offering a relatively non-invasive, safe, portable, and low-cost method of indirect and direct monitoring of brain activity. Most exciting is its potential to allow more ecologically valid investigations that can translate laboratory work into more realistic everyday settings and clinical environments. Our aim is to acquaint clinicians and researchers with the unique and beneficial characteristics of fNIRS by reviewing its relative merits and limitations vis-à-vis other brain-imaging technologies such as functional magnetic resonance imaging (fMRI). We review cross-validation work between fMRI and fNIRS, and discuss possible reservations about its deployment in clinical research and practice. Finally, because there is no comprehensive review of applications of fNIRS to brain disorders, we also review findings from the few studies utilizing fNIRS to investigate neurocognitive processes associated with neurological (Alzheimers disease, Parkinsons disease, epilepsy, traumatic brain injury) and psychiatric disorders (schizophrenia, mood disorders, anxiety disorders).

Clock drawing errors in dementia: neuropsychological and neuroanatomical considerations.

Objectives:A clock drawing test scoring system is presented to explore the neuropsychological/neuroanatomic components underlying clock drawing in patients initially diagnosed with Alzheimer disease, ischemic vascular dementia associated with white matter alterations, and Parkinson disease. Methods:Fourteen clock drawing test errors were scored to create 4 clock drawing test subscales that assess different underlying cognitive operations. Results:In the command condition, errors on the Time subscale were correlated with impairment on executive control measures. In the copy condition, errors on the Perseveration/Pull to Stimulus subscale was also correlated with executive control measures. Patients presenting with mild (low) magnetic resonance imaging white matter alterations, significant (high) white matter alterations, and Parkinson disease were compared. In the command condition, the low white matter alterations group made fewer total errors than the Parkinson disease group. In the copy condition, the low white matter alterations group made fewer errors on the Time, Spatial Layout, and Perseveration/Pull to Stimulus clock drawing test subscales than the high white matter alterations or Parkinson disease groups. Few differences were noted between the high white matter alterations and Parkinson disease groups. Discussion:Our data suggest that heavy demands on executive control associated with the interruption of large-scale cortical–subcortical neural networks underlie impairment in clock drawing in mild dementia.

Retrograde State Dependent Learning

Sodium pentobarbital administered intravenously after acquisition in a one-trial passive avoidance task results in state dependent (drug dissociated) learning in male albino rats. Findings have methodological implications for drug-based research and theoretical implications for drug discrimination studies. Predictions based on a stimulus generalization hypothesis are not supported, whereas those based on an information storage hypothesis are supported.

Medial prefrontal cortex hyperactivation during social exclusion in borderline personality disorder

Frontal systems dysfunction and abandonment fears represent central features of borderline personality disorder (BPD). BPD subjects (n=10) and matched non-psychiatric comparison subjects (n=10) completed a social-cognitive task with two confederates instructed to either include or exclude subjects from a circumscribed interaction. Evoked cerebral blood oxygenation in frontal cortex was measured using 16-channel functional near infrared spectroscopy. BPD subjects showed left medial prefrontal cortex hyperactivation during social exclusion suggesting potential dysfunction of frontolimbic circuitry.

Distinguishing between Neuropsychological Malingering and Exaggerated Psychiatric Symptoms in a Neuropsychological Setting

It is unclear whether symptom validity test (SVT) failure in neuropsychological and psychiatric domains overlaps. Records of 105 patients referred for neuropsychological evaluation, who completed the Test of Memory Malingering (TOMM), Reliable Digit Span (RDS), and Millon Clinical Multiaxial Inventory–III (MCMI–III), were examined. TOMM and RDS scores were uncorrelated with MCMI–III symptom validity indices and factor analysis revealed two distinct factors for neuropsychological and psychiatric SVTs. Only 3.5% of the sample failed SVTs in both domains, 22.6% solely failed the neuropsychological SVT, and 6.1% solely failed the psychiatric SVT. The results support a dissociation between neuropsychological malingering and exaggeration of psychiatric symptoms in a neuropsychological setting.

Abnormal prefrontal cortical response during affective processing in borderline personality disorder.

Emotion dysregulation is a hallmark feature of borderline personality disorder (BPD) and is associated with a dysfunction of prefrontal (PFC)-limbic systems. The purpose of the present study was to examine PFC function in BPD during the experience and suppression of sadness. Subjects were females with BPD (N=9) and age-, gender-, and IQ-matched non-psychiatric comparison subjects (N=8). Evoked hemodynamic oxygenated hemoglobin (oxy-Hb) was examined in PFC using functional near-infrared spectroscopy while subjects viewed neutral or sad images and were instructed to either maintain or suppress their emotional reactions. No group differences in behavioral ratings of sadness suppression or mean levels of evoked oxy-Hb were observed. BPD and control subjects, however, recruited homologous regions of lateral PFC during emotional suppression, with right lateral PFC activation for BPD subjects associated with difficulty suppressing sadness, whereas an inverse relationship was observed in left lateral PFC for healthy controls. Exploratory analyses revealed that the slope of the rise in oxy-Hb in medial PFC during transient sadness was positive and steep for healthy controls. Conversely, BPD subjects showed a negative and shallow slope, which was associated with severity of clinical symptoms. These results suggest that BPD subjects may show abnormal evoked oxy-Hb in medial PFC during transient sadness, with recruitment of right lateral PFC in BPD associated with reported difficulty in suppressing emotion. This abnormal cortical response, possibly in tandem with subcortical-limbic regions, may underlie symptoms of emotion dysregulation in BPD.

Accurate millisecond timing on Apple’s Macintosh using Drexel’s MilliTimer

Many of the timed functions that concern psychologists, such as perceptual presentations and reaction time, are sensitive to a maximum variability in display timing caused by screen-refresh characteristics. For the Apple Macintosh, the screen operating speed is 60 Hz, which translates to an average of 8.33-msec variability. For microcomputers other than the Macintosh, a variety of hardware and software modifications to generate millisecond timing have become standard (e.g., Reed, 1979). Other than Reed College’s (1985) implementation in Rascal, which requires the Rascal development language, there has been no method of which we were aware to synchronize experimental timing with display presentation on the Macintosh. This limitation in the usefulness of the Macintosh as an otherwise excellent research tool can be overcome using Drexel University’s MilliTimer. The assembler code which follows should be considered in the public domain and can be readily adapted to any of the Macintosh-based languages.

How Does the Brain Support Script Comprehension? A Study of Executive Processes and Semantic Knowledge in Dementia

The neuropsychological substrate of scripts, routines which guide much of human behavior, is unclear. We propose a model of script comprehension characterized by the interaction of semantic knowledge for script content, and executive resources that organize this knowledge into goal directed behavior. We examined these neuropsychological components by asking participants with Alzheimers disease (AD) and frontotemporal dementia (behavioral disorder/dysexecutive syndrome (BDD) and semantic dementia (SD) subtypes), to judge the coherence of four-phrase scripts. The BDD group detected significantly fewer sequencing errors than semantic errors; the AD and SD groups detected these errors with equal frequency. Independent semantic measures predicted both semantic and sequencing script errors, while executive measures predicted sequencing errors only. Findings support a multi-component model of script comprehension.

Decreased phosphorylation of synaptic glycoproteins following hippocampal kindling

Rats with chronic electrode implants to region CA3 of the hippocampus were rapidly kindled by stimulation with a 10 s, 10 Hz train of biphasic square waves presented every 5 min, until generalized seizures developed (60-70 stimulations). The hippocampi were isolated from the brains of control animals (implanted but not stimulated), and experimental animals which had developed generalized seizures. Synaptic membranes (SM) were prepared. SM were incubated with [gamma-32P]ATP and the incorporation of 32P into proteins and glycoproteins isolated by affinity chromatography on concanavalin-A-agarose was investigated. There was no difference in the phosphorylation pattern of total SM proteins between groups. In contrast, the phosphorylation of a glycoprotein with an apparent molecular weight of 180,000 was decreased 20-40% in kindled animals. This result was replicated in three independent experiments. The results suggest that the phosphorylation of glycoprotein 180 may be related to neuroplastic events.

MacLaboratory for psychology: General experimental psychology with Apple’s Macintosh

Every student at Drexel University is required, on admission, to purchase a Macintosh computer. Consequently, there is an understandable demand to effectively utilize this resource in the undergraduate curriculum. We have developed what amounts to a series of “take-home” programs that convert the Macintosh into a number of “pieces” of experimental psychology equipment. Providing each student with a personal psychology “MacLaboratory” has apparent pedagogical and practical benefits, from creative hands-on experience to ease of independent research. This paper summarizes details of the program to date, its development process, supporting materials, and our experience when every student has a personal computer.