Linda Isaac

The psychophysiology of generalized anxiety disorder: 1. Pretreatment characteristics

Generalized anxiety disorder (GAD) patients have been reported to have more muscle tension than controls, which has provided a rationale for treating them with muscle relaxation therapies (MRT). We tested this rationale by comparing 49 GAD patients with 21 controls. Participants underwent 5-min relaxation tests, during which they either just sat quietly (QS) or sat quietly and tried to relax (R). GAD patients reported themselves to be more worried during the assessment than the controls, had higher heart rates and lower end-tidal pCO2, but not higher muscle tension as measured by multiple EMGs. QS and R did not differ on most psychological and physiological measures, indicating that intention to relax did not affect speed of relaxation. In the GAD group, self-reported anxiety was not associated with electromyographic or autonomic measures. We conclude that GAD is not necessarily characterized by chronic muscle tension, and that this rationale for MRT should be reconsidered.

The impact of depression on veterans with PTSD and traumatic brain injury: a diffusion tensor imaging study

A significant proportion of military personnel deployed in support of Operation Enduring Freedom and Operation Iraqi Freedom were exposed to war-zone events associated with traumatic brain injury (TBI), depression (DEP) and posttraumatic stress disorder (PTSD). The co-occurrence of TBI, PTSD and DEP in returning Veterans has recently increased research and clinical interest. This study tested the hypothesis that white matter abnormalities are further impacted by depression. Of particular relevance is the uncinate fasciculus (UF), which is a key fronto-temporal tract involved in mood regulation, and the cingulum; a tract that connects to the hippocampus involved in memory integration. Diffusion tensor imaging (DTI) was performed on 25 patients with a combination of PTSD, TBI and DEP and 20 patients with PTSD and TBI (no DEP). Microstructural changes of white matter were found in the cingulum and UF. Fractional anisotropy (FA) was lower in Veterans with DEP compared to those without DEP.

The psychophysiology of generalized anxiety disorder: 2. Effects of applied relaxation

Muscle relaxation therapy assumes that generalized anxiety disorder (GAD) patients lack the ability to relax but can learn this in therapy. We tested this by randomizing 49 GAD patients to 12 weeks of Applied Relaxation (AR) or waiting. Before, during, and after treatment participants underwent relaxation tests. Before treatment, GAD patients were more worried than healthy controls (n=21) and had higher heart rates and lower end-tidal pCO2, but not higher muscle tension (A. Conrad, L. Isaac, & W.T. Roth, 2008). AR resulted in greater symptomatic improvement than waiting. However, 28% of the AR group dropped out of treatment and some patients relapsed at the 6-week follow-up. There was little evidence that AR participants learned to relax in therapy or that a reduction in anxiety was associated with a decrease in activation. We conclude that the clinical effects of AR in improving GAD symptoms are moderate at most and cannot be attributed to reducing muscle tension or autonomic activation.

Coherence Between Attentional and Memory Biases in Sad and Formerly Depressed Individuals

Cognitive theories assume a uniform processing bias across different samples, but the empirical support for this claim is rather weak and inconsistent. Therefore, coherence between biases across different cognitive domains in a sample of 133 non-depressed (Study 1) and a sample of 266 formerly depressed individuals (Study 2) was examined. In both studies, individuals were selected after a successful sad mood induction procedure. A Dot Probe task, an Emotional Stroop task and a self-referential Incidental Learning and Free Recall task were administered to all participants. Principle component analyses indicated coherence between attentional and memory bias in non-depressed, while in formerly depressed individuals distinct components for attentional biases and for memory bias were uncovered. The data suggest that in formerly depressed individuals, self-referent processing during encoding may be related to memory bias, whereas in non-depressed individuals memory bias may be related to both attentional bias and self-referent processing.

Shorter gaze duration for happy faces in current but not remitted depression: Evidence from eye movements

Cognitive theories of depression propose that depressed individuals preferentially attend to negative information and that such cognitive biases constitute important vulnerability and maintenance factors for the disorder. Most studies examined this bias by registration of response latencies. The present study employed a direct and continuous measurement of attentional processing for emotional stimuli by recording eye movements. Currently depressed (CD), remitted depressed (RD) and healthy control (HC) participants viewed slides presenting sad, angry, happy and neutral facial expressions. For each expression, four components of visual attention were analyzed: first fixation, maintained fixation, relative fixation frequency and glance duration. Results showed that healthy controls were characterized by longer gaze duration for happy faces compared to currently depressed individuals but not compared to remitted depressed individuals. Both patient groups (CD, RD) demonstrated longer maintained fixation (dwelling time) on all emotional faces compared to healthy controls. The present findings are in line with the presumption that depression is associated with a loss of elaborative processing of positive stimuli that characterizes healthy controls. Importantly, successful remission of depression (RD group) may result in positive attentional processing as no group differences were found between healthy controls and remitted patients on glance duration for happy faces.

Challenges to be overcome using population-based sampling methods to recruit veterans for a study of post-traumatic stress disorder and traumatic brain injury

BackgroundMany investigators are interested in recruiting veterans from recent conflicts in Afghanistan and Iraq with Traumatic Brain Injury (TBI) and/or Post Traumatic Stress Disorder (PTSD). Researchers pursuing such studies may experience problems in recruiting sufficient numbers unless effective strategies are used. Currently, there is very little information on recruitment strategies for individuals with TBI and/or PTSD. It is known that groups of patients with medical conditions may be less likely to volunteer for clinical research. This study investigated the feasibility of recruiting veterans returning from recent military conflicts— Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) - using a population-based sampling method.MethodsIndividuals were sampled from a previous epidemiological study. Three study sites focused on recruiting survey respondents (n = 445) who lived within a 60 mile radius of one of the sites.ResultsOverall, the successful recruitment of veterans using a population-based sampling method was dependent on the ability to contact potential participants following mass mailing. Study enrollment of participants with probable TBI and/or PTSD had a recruitment yield (enrolled/total identified) of 5.4%. We were able to contact 146 individuals, representing a contact rate of 33%. Sixty-six of the individuals contacted were screened. The major reasons for not screening included a stated lack of interest in the study (n = 37), a failure to answer screening calls after initial contact (n = 30), and an unwillingness or inability to travel to a study site (n = 10). Based on the phone screening, 36 veterans were eligible for the study. Twenty-four veterans were enrolled, (recruitment yield = 5.4%) and twelve were not enrolled for a variety of reasons.ConclusionsOur experience with a population-based sampling method for recruitment of recent combat veterans illustrates the challenges encountered, particularly contacting and screening potential participants. The screening and enrollment data will help guide recruitment for future studies using population-based methods.

Depression in Men and Women One Year Following Traumatic Brain Injury (TBI): A TBI Model Systems Study

In the general population, females experience depression at significantly higher rates than males. Individuals with traumatic brain injury (TBI) are at substantially greater risk for depression compared to the overall population. Treatment of, and recovery from, TBI can be hindered by depression; comorbid TBI and depression can lead to adverse outcomes and negatively affect multiple aspects of individuals’ lives. Gender differences in depression following TBI are not well understood, and relevant empirical findings have been mixed. Utilizing the Patient Health Questionnaire-9 (PHQ-9) 1 year after TBI, we examined whether women would experience more severe depressive symptoms, and would endorse higher levels of depression within each category of depression severity, than would men. Interestingly, and contrary to our hypothesis, men and women reported mild depression at equal rates; PHQ-9 total scores were slightly lower in women than in men. Men and women did not differ significantly in any PHQ-9 depression severity category. Item analyses, yielded significant gender differences on the following items: greater concentration difficulties (cognitive problems) in men and more sleep disturbances (psychosomatic issues) in women per uncorrected two-sample Z-test for proportions analyses; however, these results were not significant after the family-wise Bonferroni correction. Our results indicate that, in contrast to the general population, mild depression in persons with moderate to severe TBI may not be gender-specific. These findings underscore the need for early identification, active screening, and depression treatment equally for men and women to improve emotional well-being, promote recovery, and enhance quality of life following TBI.

Eeg Coherence between Prefrontal and Posterior Cortical Regions is Related to Negative Personality Traits

Despite the high prevalence of mood disorders, their underlying psychopathology remains poorly understood. A recent publication by Reiser et al. (2012) in Brain and Cognition describes a possible mechanism underlying the development and maintenance of attentional bias in depression and anxiety. Their findings regarding decoupling of prefrontal–posterior brain regions adds to the existing evidence that fronto-limbic interactions facilitate the generation of task-relevant responses while inhibiting interference from emotionally distracting information. The authors employed electroencephalogram (EEG) and three mood induction methods (sad, anxious, and neutral moods) in healthy controls to explore state-dependent coherence between prefrontal and posterior cortical regions as a mechanism for modulating the impact that social-emotional information has on an individual. The findings suggest that prefrontal–posterior decoupling is related to individual differences in the behavioral traits of absorption and in the propensity to ruminate. Higher scores in these traits were related to loosened coupling between prefrontal cortex (PFC) and posterior cortex. Conversely, healthy controls with lower scores on absorption and rumination showed stronger prefrontal–posterior coupling. Results were interpreted as showing that less prefrontal–posterior coupling may be related to loosening of control by the PFC over incoming social-emotional information, and consequently to deeper emotional involvement and absorption. Conversely, increased prefrontal–posterior coupling may be related to strong control, with a consequent dampening of emotional experience and a lack of emotional engagement. When considering the neural substrates of emotional control, the limbic system has been suggested to play a key role. This set of brain regions includes frontal and medial temporal lobe structures. Although there is no universally accepted definition of what constitutes the limbic system, the anterior cingulate cortex (ACC) is thought to play an important role in emotional regulation. Numerous other functions have been ascribed to the ACC but here we focus on the specific role of the ACC on regulating emotion through attentional control. The ACC can be divided into dorsal (cognitive), and ventral (emotional) components. The dorsal ACC is thought to monitor for errors or processing conflicts that could disrupt performance and to recruit the dorsolateral PFC (DLPFC) to reallocate attentional resources as needed (Allman, et al., 2001). Specifically, cognitive reallocation by the ACC is thought to be activated by demanding tasks that involve stimulus-response selection in the face of competing streams of information such as emotionally valenced distractions. The authors did not include a task that forced the engagement of this reallocation system to better account for the relationship between mood and inhibitory deficits. This could have been accomplished for example by employing a classic EEG paradigm (Go/NoGo). Moreover, while methods such as high-density EEG, independent component analysis and surface Laplacian estimation afford the opportunity for greater spatial resolution of cognitive tasks, it is the temporal precision of EEG compared to other imaging methods which leads to its superiority in such experiments. As a result, this technique could have been utilized to understand “when” (not just where) the decoupling occurs and whether time-course differences could provide additional explanatory power to differentiate between individual differences in absorption or rumination. Similar questions could also be asked of patient groups. For example, does decreased prefrontal–posterior EEG coherence in patients with anxiety disorders occur earlier (vigilant orientation) compared to those with depression (disengagement deficits or perseverative errors) during affective challenges? A neurophysiological index of prefrontal inhibitory control was detected with a negative-going deflection peaking between 250 and 350  ms after the onset of NoGo distractors. This phasic negativity often peaks in midfrontal scalp regions and has been considered to be the electrophysiological correlate of ACC function involved in sustained attention, error detection, and response control. Thus, the N2 component of the event-related potential, an evoked response presumably generated within the ACC, is significantly enhanced when individuals successfully inhibit a response, and therefore provides an excellent neurophysiologic metric of frontal inhibitory function (Nieuwenhuis et al., 2003). Importantly, recent research has demonstrated inhibitory dysfunction in depression and anxiety, and this deficit is likely to be valence-specific. It is often referred to as attentional bias, broadly defined as the preferential processing of mood-congruent stimuli over neutral stimuli. Attentional bias is perhaps the clearest example of when the ACC-DLPFC relationship is unsuccessful through a failure to ward off emotional distracters. We propose that stimulus control is essential in defining models of inhibitory deficits for both depression and anxiety. For instance, one can imagine there may be differences in prefrontal–posterior EEG coherence when comparing an angry face with an averted vs. a direct gaze because the latter signals impending threat toward the observer. We also argue that the process of experimental mood induction is not always straightforward. For instance, observing a sad person does not necessarily induce a sad mood in a participant as this bears no direct relevance or importance to them. In fact, an angry face may be more salient to a sad or depressed observer than a control participant due to the message of rejection or disapproval (Isaac et al., 2012). The authors accordingly note that mood induction is transient, and, as we have found in our own research, manipulation checks in mood induction designs are especially important because moods can occur concomitantly (sad and anxious) or change from sad to anxious during the experiment. Interestingly, the authors also asked participants in the three mood states to rate additional emotions, including disgust. This more complex emotion recruits different brain regions such as the orbito-frontal and insular cortices commonly affected in neurological disorders. Specifically, disgust has been observed to be compromised in neurodegenerative diseases, such as the behavioral variant of fronto-temporal dementia (Sturm et al., 2006), rather than affective disorders. Excitingly, the decoupling hypothesis, sometimes referred to as “hypofrontality,” is applicable to a host of psychological disorders apart from depression and anxiety, and thus holds high explanatory value for what could be a common causal mechanism for the development and maintenance of psychopathology in general. For instance, several strands of functional neuroimaging evidence have shown PFC dysfunction in schizophrenia, with specific evidence for reduced attentional control relative to controls during emotional distraction and deactivation failure during cognitive tasks (Dichter et al., 2010). In depressed subjects, increased limbic activity has been shown in response to emotional stimuli, and decreased DLPFC activity during cognitive tasks (Siegle et al., 2007). This may indicate an inability to effectively recruit the DLPFC, leading to a failure to inhibit limbic activity, especially in the presence of task-irrelevant and novel valenced stimuli. Interestingly, lower DLPFC and ACC activation levels also characterize high-risk groups, such as formerly depressed participants (Hooley et al., 2009), suggesting that an altered cortico-limbic relationship is not necessarily reversed by successful treatment of such disorders. This observation has ignited debates about whether hypofrontality is a cause or consequence of disease and if disease can be ameliorated by identifying hypofrontality in subclinical groups (e.g., dysthymic patients). Future studies are required to determine whether alterations in frontal activation correlate with disease symptoms and therefore constitute a risk factor for psychiatric illness. Importantly, the study by Hooley et al. (2009) suggests that self-report measures and clinical status are not sufficient for detecting what may be subtle deficiencies in the reciprocal relationship between the DLPFC and ACC. It argues for the use of neuroimaging techniques that are sensitive enough to detect such subtleties. The elucidation of the neural circuitry underlying the control of emotional experience contributes significantly to our comprehension of the symptoms of depression and anxiety, such as rumination and hypervigilance, respectively. For example, depressed patients may succeed at conflict detection in the form of hypersensitivity to negative cues evidenced by the engagement of a key emotional processing structure (amygdala) but fail on tasks requiring conflict resolution that involve cognitive control (DLPFC-ACC). We suggest that closing the loop between the emotional and the cognitive brain is central to progress in the treatment of emotional disorders. These reciprocal regulatory mechanisms constitute a critical property of human adaption that facilitates the balance between processing task-relevant information and emotionally salient but task-irrelevant information. Successful goal directed behavior appears to be mediated by direct feedback connections between the DLPFC and the ACC especially when emotional distracters are present.

SCiPad: Effective Implementation of Telemedicine Using iPads with Individuals with Spinal Cord Injuries, a Case Series

Background Individuals with spinal cord injury (SCI) must often travel long distances to see a rehabilitation specialist. While telemedicine (TM) for pressure ulcer management has been used in this population, real-time video telecommunication using iPad has never been described. Objective The objective of this study was to provide specialized care for persons with SCI through TM consultation expediently in order to address medical needs, manage secondary complications, and to improve quality of life (QoL) of individuals with SCI. Methods Ten individuals with SCI participated in the TM program using iPads for 6 months as a feasibility study at a single-center, county hospital. The participants contacted the project staff for SCI-related conditions and were then connected to an SCI-trained health-care provider within 24 hours via FaceTime. Main outcome measures included health-care utilization; QoL and psychosocial measures collected at baseline and at 6 months: Reintegration to Normal Living Index (RNLI), Life Satisfaction Index A (LSI-A), and Patient Health Questionnaire 9 (PHQ-9); and a Program Satisfaction Survey. Results Ten patients (seven with tetraplegia, three with paraplegia; eight males and two females) with an average age of 34.4 (18–54) years were enrolled. The average baseline and 6-month follow-up scores were RNLI—70.1 ± 19.7 and 74.7 ± 21.8, respectively; LSI-A—25.4 ± 7.4 and 26.4 ± 8.2, respectively; and PHQ-9 were 6.8 ± 7.2 and 8.6 ± 6.1, respectively. TM encounters included topics such as pain, bladder and skin management, medication changes, and lab results. The Program Satisfaction Survey yielded positive results with 100% of program completers stating they would recommend the program and would like to continue having TM. Conclusion This is the first known successful project using iPad to provide TM in the SCI population. This study discusses the implementation of such a TM program in a health system including limitations. It describes the clinical viability of TM using iPads in the SCI population for care beyond that of just pressure ulcer management. This project provides evidence for using a tablet device like an iPad as an effective and efficient patient management tool.

The Effect of Vitamin D Supplementation on Pain, Mood, Depression, and Strength in Patients with Spinal Cord Injury

Setting: Tertiary care pediatric hospital. Participants: A total of 134 children (61% male and 39% female) received botulin toxin type A injections for treatment of refractory CMT between 2004 and 2013. Interventions: Each infant was injected with 15 to 30 units of botulinum toxin type A following standard clinical procedure into each of the following muscles: the sternocleidomastoid, upper trapezius, and scalene muscles. Main Outcome Measures: Key outcome measures analyzed for each subject included age at time of diagnosis, age at time of initiation of physical therapy, age at time of injection, total number of injection series utilized, muscles injected, and degrees of active and passive cervical rotation and lateral flexion preand post-injection. A successful outcome was documented if a child could achieve 45 of active lateral flexion and 80 of active cervical rotation postinjection. Results: Eighty-two children (61%) had successful outcomes. When breaking it down by each motion, 83 (62%) achieved success when only accounting for lateral flexion, while 112 (84%) achieved success when only accounting for cervical rotation. When reviewing the characteristics of the children there was no significant determinant when predicting a successful outcome. Conclusions: Botulinum toxin is a safe and effective method for treatment in refractory cases of congenital muscular torticollis. Level of Evidence: Level III