Anthony C. Ruocco

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).

The neuropsychology of borderline personality disorder: A meta-analysis and review

The neuropsychological profile of borderline personality disorder (BPD) is unclear. Past investigations have produced seemingly inconsistent results concerning precisely what neuropsychological deficits characterize the patient with BPD. A meta-analysis of 10 studies was conducted comparing BPD and healthy comparison groups on selected neuropsychological measures comprising six domains of functioning: attention, cognitive flexibility, learning and memory, planning, speeded processing, and visuospatial abilities. BPD participants performed more poorly than controls across all neuropsychological domains, with mean effect sizes (Cohens d) ranging from -0.29 for cognitive flexibility to -1.43 for planning. The results suggest that persons with BPD perform more poorly than healthy comparison groups in multiple neurocognitive domains and that these deficits may be more strongly lateralized to the right hemisphere. Although neuropsychological testing appears to be sensitive to the neurocognitive deficits of BPD, the clinical utility of these results is limited. Implications of these findings for future neurocognitive investigations of BPD are discussed.

Neural Correlates of Negative Emotionality in Borderline Personality Disorder: An Activation- Likelihood-Estimation Meta-Analysis

BACKGROUND Emotional vulnerabilities at the core of borderline personality disorder (BPD) involve a dysfunction of frontolimbic systems subserving negative emotionality. The specific regions identified in individual studies, however, vary widely and provide an incomplete understanding of the functional brain abnormalities that characterize this illness. A quantitative synthesis of functional neuroimaging studies might clarify the neural systems dysfunctions that underlie negative emotionality in BPD. METHODS An electronic search of Medline and PsycInfo databases from 2000 to 2012 identified 18 potential studies, of which 11 met inclusion criteria for the meta-analysis and comprised a pooled sample of 154 BPD patients and 150 healthy control subjects. Contrasts of negative versus neutral emotion conditions were analyzed with an activation-likelihood-estimation meta-analytic approach. Group comparisons were performed on study-reported between-subjects contrasts and independent subtraction analyses based on within-subjects contrasts. RESULTS Healthy control subjects activated a well-characterized network of brain regions associated with processing negative emotions that included the anterior cingulate cortex and amygdala. Compared with healthy control subjects, BPD patients demonstrated greater activation within the insula and posterior cingulate cortex. Conversely, they showed less activation than control subjects in a network of regions that extended from the amygdala to the subgenual anterior cingulate and dorsolateral prefrontal cortex. CONCLUSIONS Processing of negative emotions in BPD might be subserved by an abnormal reciprocal relationship between limbic structures representing the degree of subjectively experienced negative emotion and anterior brain regions that support the regulation of emotion. Contrary to early studies, BPD patients showed less activation than control subjects in the amygdala under conditions of negative emotionality.

Subthalamic nucleus deep brain stimulation for severe idiopathic dystonia: impact on severity, neuropsychological status, and quality of life

OBJECT Medically refractory dystonia has recently been treated using deep brain stimulation (DBS) targeting the globus pallidus internus (GPI). Outcomes have varied depending on the features of the dystonia. There has been limited literature regarding outcomes for refractory dystonia following DBS of the subthalamic nucleus (STN). METHODS Four patients with medically refractory, predominantly cervical dystonia underwent STN DBS. Intraoperative assessments with the patients in a state of general anesthesia were performed to determine the extent of fixed deformities that might predict outcome. Patients were rated using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) preoperatively and 3 and 12 months following surgery by a rater blinded to the study. Mean changes and standard errors of the mean in scores were calculated for each subscore of the two scales. Scores were also analyzed using analysis of variance and probability values were generated. Neuropsychological assessments and quality of life ratings using the 36-Item Short Form Health Survey (SF-36) were evaluated longitudinally. RESULTS Significant improvements were seen in motor (p = 0.04), disability (p = 0.02), and total TWSTRS scores (p = 0.03). Better outcomes were seen in those patients who did not have fixed deformities. There was marked improvement in the mental component score of the SF-36. Neuropsychological function was not definitively impacted as a result of the surgery. CONCLUSIONS Deep brain stimulation of the STN is a novel target for dystonia and may be an alternative to GPI DBS. Further studies need to be performed to confirm these conclusions and to determine optimal candidates and stimulation parameters.

Amygdala and hippocampal volume reductions as candidate endophenotypes for borderline personality disorder: A meta-analysis of magnetic resonance imaging studies

Borderline personality disorder (BPD) is a genetically influenced psychiatric illness with disruptions in neural systems supporting cognition and emotion regulation. Volumetric decreases of the hippocampus and amygdala may characterize BPD and serve as putative endophenotypes for the illness. The purpose of the present study was to evaluate whether the magnitude of these volume reductions and their associations with state-of-illness factors and psychiatric disorders which often co-occur with BPD warrant their consideration as potential endophenotypes. Volumetric magnetic resonance imaging results from 11 studies comprising 205 BPD patients and 222 healthy controls were quantitatively synthesized using meta-analytic techniques. Patients showed an average 11% and 13% decrease in the size of the hippocampus and amygdala, respectively. These volumetric differences were not attenuated in patients being treated with psychotropic medications. Comorbid depression, post-traumatic stress disorder, and substance use disorders were unrelated to volumetric decreases in either structure. These findings suggest modest volume reductions of the amygdala and hippocampus bilaterally in BPD which cannot be attributed to illness state or comorbid psychopathology. Decreased volumes of these key limbic structures may hold promise as candidate endophenotypes for BPD.

Dual-modality monitoring in a classification task: The effects of bilingualism and ageing

Two experiments are reported in which monolingual and bilingual participants who were younger (Experiment 1) or older (Experiment 2) adults performed in a dual-task classification paradigm. Visually (primary task) and auditorily (secondary task) presented stimuli were classified into two categories. The stimuli belonged to two domains, letters or numbers (LN) and animals or musical instruments (AM), and the two task modalities used stimuli from the same (related) or opposite (unrelated) domains. For both age groups, bilinguals were less disrupted than monolinguals in visual sorting in the LN domain, and relatedness affected performance only in the AM domain. The results indicate different processing demands for the two domains, with the simpler domain (LN) favouring bilinguals and the more semantically complex domain (AM) favouring related judgements for the two task modalities.

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.

Reduced Levels of Vasopressin and Reduced Behavioral Modulation of Oxytocin in Psychotic Disorders

Oxytocin (OT) and arginine vasopressin (AVP) exert robust influence on social affiliation and specific cognitive processes in healthy individuals. Abnormalities in these neuroendocrine systems have been observed in psychotic disorders, but their relation to impairments in behavioral domains that these endocrines modulate is not well understood. We compared abnormalities of OT and AVP serum concentrations in probands with schizophrenia (n = 57), schizoaffective disorder (n = 34), and psychotic bipolar disorder (n = 75); their first-degree relatives without a history of psychosis (n = 61, 43, 91, respectively); and healthy controls (n = 66) and examined their association with emotion processing and cognition. AVP levels were lower in schizophrenia (P = .002) and bipolar probands (P = .03) and in relatives of schizophrenia probands (P = .002) compared with controls. OT levels did not differ between groups. Familiality estimates were robust for OT (h(2) = 0.79, P = 3.97e-15) and AVP (h(2) = 0.78, P = 3.93e-11). Higher levels of OT were associated with better emotion recognition (β = 0.40, P < .001) and general neuropsychological function (β = 0.26, P = .04) in healthy controls as expected but not in any proband or relative group. In schizophrenia, higher OT levels were related to greater positive symptom severity. The dissociation of OT levels and behavioral function in all proband and relative groups suggests that risk and illness factors associated with psychotic disorders are not related to reduced OT levels but to a disruption in the ability of physiological levels of OT to modulate social cognition and neuropsychological function. Decreased AVP levels may be a marker of biological vulnerability in schizophrenia because alterations were seen in probands and relatives, and familiality was high.

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.