In the theory of the Behavioral Inhibition System (BIS), Gray and McNaughton (2000) classified events that produce or inhibit goal-directed behaviour into two affective categories: approach versus avoidance. We experience goal-conflict when approximately equal but incompatible approach and avoidance tendencies are concurrently activated. Gray and McNaughton (2000) proposed goal-conflict as a class of mechanisms separable from "simple" mechanisms: Goal-conflict effects are maximal when incompatible approach and avoidance tendencies are balanced, simple effects are maximal when either approach or avoidance tendencies predominate. Gray and McNaughton (2000) saw the hippocampus as a key nexus for resolving goal conflict by recursive amplification of the subjective value of punishment, thereby increasing avoidance tendencies. Rodent hippocampal theta (4-12 Hz) is necessary (but not sufficient) for correct and efficient transmission of hipppocampal outputs. The BIS theory is fundamentally an animal model. It is not clear if a human BIS exists in the same form. Record human hippocampal (4-12 Hz) activity from the scalp is unlikely. However, during goal-conflict resolution, cortically generated theta recorded from the scalp could be modulated by human hippocampal theta. Therefore, superficially recorded 4-12 Hz theta spectra power was used to assess if specific goal-conflict processing activity could be detected in humans. Human goal-conflict processing was assessed in four experiments: the Stop-Signal Task (SST), an existing experimental task, and three variations of a task termed "Choice", created for this thesis. Across experiments, three key conditions were created. Approach and avoidance were balanced in the intermediate condition (maximal goal-conflict). Net approach and avoidance predominated in the adjacent conditions respectively (minimal goal-conflict). Goal-conflict was assessed as the difference between activity in the intermediate condition and the average activity across the adjacent conditions (via extraction of the orthogonal quadratic trend for significance testing). Goal-conflict increased activations consistently at F8, above the right frontal cortex. Increase in task dependent goal-conflict activations were also observed at F7, Fz and F4 above the frontal cortex, and T3, T4, T5 and T6 above the temporal cortex. Activations within the human theta frequency range (4-7 Hz) were consistently detected in the Choice tasks. In the SST, activations spanned the conventional human theta (4-7 Hz) and alpha (8-12 Hz) frequencies. In the Choice tasks, higher conflict theta at T3, T5 and F8 predicted increased avoidance. Taken together, the findings support Gray and McNaugthon�s (2000) views that a) goal-conflict is a class of mechanism separable from simple approach and avoidance; b) goal-conflict processing recruits and increases cortical rhythmic activity within the same frequency range as rodent hippocampal theta (4-12 Hz); and goal-conflict is resolved by increasing the subjective value of punishment, thereby increasing avoidance tendencies. Although speculative, the current work identified a right inferior frontal gyrus neural circuit for slower, and a presupplementary motor area circuit for faster behavioral inhibition during goal-conflict resolution. These circuits are not explicit in the current BIS model.

Doctor of Philosophy(PhD) / The experience of persistent fatigue after breast cancer treatment is estimated to affect approximately one in four women, but fatigue development and factors associated with cancer-related fatigue are poorly understood. Gaining a better understanding of these issues is important because persistent fatigue after radiation therapy can be a debilitating experience for cancer survivors. The objectives of this study were: (1) to determine fatigue prevalence in women with breast cancer at standardised timepoints after radiation therapy; (2) to investigate the relationships between fatigue, salivary cortisol rhythm and thyroid function; (3) to investigate the amount of radiation dose received by the thyroid gland in different radiation therapy treatment techniques; and (4) to investigate the relationship between irradiation of the thyroid, thyroid function and fatigue. Participants in this research were women diagnosed with non-metastatic breast cancer and all were referred for adjuvant radiation therapy treatment. One cohort of participants (n = 48) was assessed prior to the start of radiation therapy and then six months after treatment, and a second cohort (n = 15) was assessed at six months and then at 12 months after treatment. Behavioural assessments included questionnaires that measured the level of multidimensional fatigue (MFSI–SF), the degree of fatigue and depression symptoms (SPHERE–12), impact that fatigue had on participants’ functioning (FIS) and aspects of quality of life (EORTC QLQ–C30). Biological assessments included a three day measurement of salivary cortisol rhythm and an assessment of thyroid function (TSH, free T4 and free T3). Radiation doses to the thyroid gland were determined from participants’ treatment plans. Six months after completing adjuvant radiation therapy, women receiving treatment for breast cancer experienced significant improvements in emotional fatigue, role functioning and social functioning. High fatigue levels were prevalent in 29% of women at six months and 33% of women at 12 months after treatment, but newly developed fatigue that was not present before treatment was only found in 5% of participants. There were no significant changes in cortisol rhythm over time or between fatigued and non-fatigued participants; however, significant positive correlations were found between fatigue and morning cortisol. Regarding thyroid function, significant decreases in free T4 hormone levels were seen from six months to 12 months after radiation therapy with larger decreases in free T4 levels being related to higher fatigue. Radiation doses to the thyroid gland were significantly higher in participants who received treatment to the regional lymphatics with a supraclavicular fossa radiation field compared to participants who received localised treatment to the breast or chest wall only. In the former, changes in thyroid function were observed, as were relationships between mean radiation dose to the thyroid and thyroid function.

Anxiety disorder is prevalent and costly. But its diagnosis is underdeveloped and treatment ad hoc. This could be corrected if the neural mechanisms of anxiety were known. All anxiolytic medications produce a decrease in rodent hippocampal theta rhythm - so hippocampal theta could underlie some types of anxiety. But, a review (Chapter 2) showed that ethanol and other anxiolytics increase FM-theta in the human scalp EEG and have other properties unlike hippocampal theta. The experiments in this thesis, therefore, tested for other potential homologues (Chapter 3) of hippocampal theta in the human EEG. The phase of hippocampal theta activity is reset in a working memory task and not an equivalent reference memory task in rats. Furthermore, low doses ethanol increases and high dose ethanol (and other anxiolytics) decrease theta activity. So, EEG was recorded from 15 scalp sites while participants performed non-verbal working memory and reference memory tasks before and after ethanol administration and assessed for the presence of phase-reset and ethanol-related changes in 5-7Hz and 8-11Hz spectral power (chapter 4 and 5). There was little general evidence for stimulus-induced phase-resetting of the ongoing EEG activity (Chapter 6). Increased post-stimulus synchronization in the theta frequency range was accompanied by increases in post-stimulus spectral power - suggesting that the synchronised activity was evoked rather than reset. Across 3 experiments (Chapter 7), low dose ethanol (54.5-146.6[mu]g/l) increased 5-7Hz theta, while the highest dose (307[mu]g/l) reduced task-related-increases in 5-7Hz activity. These effects were noted across electrode locations including frontal-midline sites and particularly at the beginning of the delay period. The suppression of 5-7Hz activity also coincided with an impairment in working memory performance. The dose-response curve for 5-7Hz theta was as predicted from rat hippocampal work. This particular component, linked to high working memory load or task difficulty, is a potential of homologue hippocampal theta. A clear decrease in theta with high dose ethanol, of this type, has not been reported previously. Activity in the 8-11Hz range typically increased with all doses of ethanol. It is clearly not a homologue of hippocampal theta. This is consistent with previous reports of increased alpha with high doses of ethanol - although these have been accompanied by increased, not decreased, theta. There is a potential homologue of hippocampal theta that can be detected in the human EEG (chapter 8); but the observed changes in 5-7Hz activity cannot be localised and may not be related to the hippocampus. It is clear there is more than one type of theta within the human EEG - with opposing sensitivities to ethanol. Critically, these types were detected at a single site and apparently in phase with one another. The current data, together with the previous literature, suggest that theta can be generated concurrently in distinct networks that, under specific task demands, can become coherent and so produce synchonised activity. Future studies need to test higher doses of ethanol and other anxiolytics and use different experimental paradigms to further differentiate the theta systems in the human EEG. Human EEG could be useful for differentiating sub-types of anxiety, and the choice and effectiveness of interventions delivered.

In the theory of the Behavioral Inhibition System (BIS), Gray and McNaughton (2000) classified events that produce or inhibit goal-directed behaviour into two affective categories: approach versus avoidance. We experience goal-conflict when approximately equal but incompatible approach and avoidance tendencies are concurrently activated. Gray and McNaughton (2000) proposed goal-conflict as a class of mechanisms separable from "simple" mechanisms: Goal-conflict effects are maximal when incompatible approach and avoidance tendencies are balanced, simple effects are maximal when either approach or avoidance tendencies predominate. Gray and McNaughton (2000) saw the hippocampus as a key nexus for resolving goal conflict by recursive amplification of the subjective value of punishment, thereby increasing avoidance tendencies. Rodent hippocampal theta (4-12 Hz) is necessary (but not sufficient) for correct and efficient transmission of hipppocampal outputs. The BIS theory is fundamentally an animal model. It is not clear if a human BIS exists in the same form. Record human hippocampal (4-12 Hz) activity from the scalp is unlikely. However, during goal-conflict resolution, cortically generated theta recorded from the scalp could be modulated by human hippocampal theta. Therefore, superficially recorded 4-12 Hz theta spectra power was used to assess if specific goal-conflict processing activity could be detected in humans. Human goal-conflict processing was assessed in four experiments: the Stop-Signal Task (SST), an existing experimental task, and three variations of a task termed "Choice", created for this thesis. Across experiments, three key conditions were created. Approach and avoidance were balanced in the intermediate condition (maximal goal-conflict). Net approach and avoidance predominated in the adjacent conditions respectively (minimal goal-conflict). Goal-conflict was assessed as the difference between activity in the intermediate condition and the average activity across the adjacent conditions (via extraction of the orthogonal quadratic trend for significance testing). Goal-conflict increased activations consistently at F8, above the right frontal cortex. Increase in task dependent goal-conflict activations were also observed at F7, Fz and F4 above the frontal cortex, and T3, T4, T5 and T6 above the temporal cortex. Activations within the human theta frequency range (4-7 Hz) were consistently detected in the Choice tasks. In the SST, activations spanned the conventional human theta (4-7 Hz) and alpha (8-12 Hz) frequencies. In the Choice tasks, higher conflict theta at T3, T5 and F8 predicted increased avoidance. Taken together, the findings support Gray and McNaugthon�s (2000) views that a) goal-conflict is a class of mechanism separable from simple approach and avoidance; b) goal-conflict processing recruits and increases cortical rhythmic activity within the same frequency range as rodent hippocampal theta (4-12 Hz); and goal-conflict is resolved by increasing the subjective value of punishment, thereby increasing avoidance tendencies. Although speculative, the current work identified a right inferior frontal gyrus neural circuit for slower, and a presupplementary motor area circuit for faster behavioral inhibition during goal-conflict resolution. These circuits are not explicit in the current BIS model.

Thesis (Ph. D.)--University of Washington, 1989. / Vita. Includes bibliographical references (leaves [62]-66).

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Washington, 1990. / Vita. Includes bibliographical references (leaves [187]-208).

Title from title page of PDF (University of Missouri--St. Louis, viewed March 22, 2010). Includes bibliographical references (p. 101-111).

Thesis (Ph. D.)--Princeton University, 1972. / Typescript. "This essay and the composition '91 plus 5' together constitute the dissertation." Includes bibliographical references (leaf 79).

Inaug.-Diss.--Kiel. / Lebenslauf. "Einleitung" includes bibliography.