A Functional Anatomy of Anticipatory Anxiety

Anticipatory anxiety is a complex combination of a future-oriented cognitive state, negative affect, and autonomic arousal. A dual-task paradigm of anticipation of electric shocks and a motor-learning task was used to examine the changes in neural patterns of activation associated with modulation of the cognitive state in anxiety by a distracting motor task. We used positron emission tomography (PET) and 15O-water to measure regional cerebral blood flow (rcbf) in 10 healthy male volunteers. A 2x2 factorial design-(shock vs no shock) x (low vs high distraction) was used with three scans per condition. Twelve PET scans were performed on each subject. In six of these scans, subjects were given electric shocks. In all scans, subjects also simultaneously performed a motor repetition (low distraction) or learning (high distraction) task. Galvanic skin conductance (GSR), Spielberger State and Trait Anxiety Inventory (STAI), and self-report data were also collected. In comparisons between the shock and no-shock conditions, the main finding was of increased rcbf in the left insula (-38,8,8) (z = 4.85, P<0.05 corrected) and a homologous area in the right insula at a lower threshold (z =3.20, P = 0.001 uncorrected). Other areas activated were the right superior temporal sulcus, left fusiform, and left anterior cingulate. Using the STAI-state scores as a covariate of interest, significant correlations with rCBF were seen in the left orbitofrontal cortex, left insula, and left anterior cingulate cortex. There was no significant distraction effect as measured by the STAI, self-report, GSR response or interactional analysis of the PET data. These findings support the role of paralimbic structures as neural substrates of anticipatory anxiety. The failure to demonstrate behavioral and neurophysiological changes with the distractor task may reflect the modest increases in anxiety with the shock, the relatively simple distractor task, and small sample size.

[1]  M. Mesulam,et al.  Insula of the old world monkey. Architectonics in the insulo‐orbito‐temporal component of the paralimbic brain , 1982, The Journal of comparative neurology.

[2]  A. Alavi,et al.  Positron emission tomographic studies of perceptual tasks , 1984, Annals of neurology.

[3]  Peter Herscovitch,et al.  A focal brain abnormality in panic disorder, a severe form of anxiety , 1984, Nature.

[4]  J R Augustine,et al.  The insular lobe in primates including humans. , 1985, Neurological research.

[5]  Trazodone treatment response in obsessive-compulsive disorder--correlated with shifts in glucose metabolism in the caudate nuclei. , 1987, Psychopathology.

[6]  J. Mazziotta,et al.  Local cerebral glucose metabolic rates in obsessive-compulsive disorder. A comparison with rates in unipolar depression and in normal controls. , 1987, Archives of general psychiatry.

[7]  The study of panic disorder using positron emission tomography. , 1987 .

[8]  E. Reiman The study of panic disorder using positron emission tomography. , 1987, Psychiatric developments.

[9]  A. Alavi,et al.  The Effect of Anxiety on Cortical Cerebral Blood Flow and Metabolism , 1987, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[10]  J. Mazziotta,et al.  Cerebral glucose metabolic rates in nondepressed patients with obsessive-compulsive disorder. , 1988, The American journal of psychiatry.

[11]  W D Obrist,et al.  Effects of task difficulty on regional cerebral blood flow: relationships with anxiety and performance. , 1988, Psychophysiology.

[12]  J. Talairach,et al.  Co-Planar Stereotaxic Atlas of the Human Brain: 3-Dimensional Proportional System: An Approach to Cerebral Imaging , 1988 .

[13]  M. Raichle,et al.  Neuroanatomical correlates of anticipatory anxiety. , 1989, Science.

[14]  D E Kuhl,et al.  Positron emission tomographic evaluation of cerebral blood flow during state anxiety in simple phobia. , 1989, Archives of general psychiatry.

[15]  J. Rapoport,et al.  Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder. , 1989, Archives of general psychiatry.

[16]  T. Nordahl,et al.  Cerebral glucose metabolic rates in obsessive compulsive disorder. , 1989, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[17]  P T Fox,et al.  Neuroanatomical correlates of a lactate-induced anxiety attack. , 1989, Archives of general psychiatry.

[18]  S. Marenco,et al.  Regional Cerebral Blood Flow and Anxiety: A Correlation Study in Neurologically Normal Patients , 1989, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[19]  M. Stein,et al.  Cerebral glucose metabolic differences in patients with panic disorder. , 1990, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[20]  A. Syrota,et al.  Obsessive‐compulsive disorder: a clinical, neuropsychological and positron emission tomography study , 1990, Acta psychiatrica Scandinavica.

[21]  PET Findings in Panic, Anxiety, and Phobic Disorders , 1991 .

[22]  E. Neafsey,et al.  The effect of medial frontal cortex lesions on respiration, "freezing," and ultrasonic vocalizations during conditioned emotional responses in rats. , 1991, Cerebral cortex.

[23]  Pietro Pietrini,et al.  Cerebral metabolic pattern in obsessive-compulsive disorder: Altered intercorrelations between regional rates of glucose utilization , 1991, Psychiatry Research: Neuroimaging.

[24]  David H. Barlow,et al.  Attention versus distraction during in vivo exposure: Snake and spider phobias , 1991 .

[25]  C. Geula,et al.  Cytoarchitecture and neural afferents of orbitofrontal cortex in the brain of the monkey , 1992, The Journal of comparative neurology.

[26]  M. Raichle,et al.  PET images of blood flow changes during anxiety: correction. , 1992, Science.

[27]  J. Mazziotta,et al.  Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. , 1992, Archives of general psychiatry.

[28]  T Greitz,et al.  Regional cerebral blood flow during experimental phobic fear. , 2007, Psychophysiology.

[29]  Mats Fredrikson,et al.  A functional cerebral response to frightening visual stimulation , 1993, Psychiatry Research: Neuroimaging.

[30]  M. Craske,et al.  The effects of distraction during exposure to phobic stimuli. , 1993, Behaviour research and therapy.

[31]  Klaus P. Ebmeier,et al.  The effect of anxiety induction on the regional uptake of 99mTc-exametazime in simple phobia as shown by single photon emission tomography (SPET). , 1993, Journal of affective disorders.

[32]  P. Pietrini,et al.  Individual differences in cerebral metabolic patterns during pharmacotherapy in obsessive-compulsive disorder: A multiple regression/discriminant analysis of positron emission tomographic data , 1993, Biological Psychiatry.

[33]  Karl J. Friston,et al.  Cerebral responses to pain in patients with atypical facial pain measured by positron emission tomography. , 1994, Journal of neurology, neurosurgery, and psychiatry.

[34]  C D Frith,et al.  Functional Anatomy of Obsessive–Compulsive Phenomena , 1994, British Journal of Psychiatry.

[35]  N. Alpert,et al.  Regional cerebral blood flow measured during symptom provocation in obsessive-compulsive disorder using oxygen 15-labeled carbon dioxide and positron emission tomography. , 1994, Archives of general psychiatry.

[36]  F Fazio,et al.  [18F]FDG PET Study in Obsessive–Compulsive Disorder , 1995, British Journal of Psychiatry.

[37]  S. Stone-Elander,et al.  Functional neuroanatomy of visually elicited simple phobic fear: additional data and theoretical analysis. , 1995, Psychophysiology.

[38]  B. Vogt,et al.  Contributions of anterior cingulate cortex to behaviour. , 1995, Brain : a journal of neurology.

[39]  Alan C. Evans,et al.  Functional neuroanatomy of CCK4-induced anxiety in normal healthy volunteers. , 1995, The American journal of psychiatry.

[40]  A. Damasio REVIEW ■ : Toward a Neurobiology of Emotion and Feeling: Operational Concepts and Hypotheses , 1995 .

[41]  N. Alpert,et al.  A positron emission tomographic study of simple phobic symptom provocation. , 1995, Archives of general psychiatry.

[42]  R T Wakai,et al.  Whole head mapping of magnetic fields following painful electric finger shock. , 1995, Brain research. Cognitive brain research.

[43]  A Deutch,et al.  A functional neuroanatomy of anxiety and fear: implications for the pathophysiology and treatment of anxiety disorders. , 1996, Critical reviews in neurobiology.

[44]  M. Fanselow,et al.  The Amygdala and Fear Conditioning: Has the Nut Been Cracked? , 1996, Neuron.

[45]  J. Gray,et al.  The neuropsychology of anxiety: reprise. , 1996, Nebraska Symposium on Motivation. Nebraska Symposium on Motivation.

[46]  D. Perrett,et al.  A differential neural response in the human amygdala to fearful and happy facial expressions , 1996, Nature.

[47]  J. R. Augustine Circuitry and functional aspects of the insular lobe in primates including humans , 1996, Brain Research Reviews.

[48]  S. Rauch,et al.  Response and Habituation of the Human Amygdala during Visual Processing of Facial Expression , 1996, Neuron.

[49]  D H Barlow,et al.  Fear, panic, anxiety, and disorders of emotion. , 1996, Nebraska Symposium on Motivation. Nebraska Symposium on Motivation.

[50]  C. E. Izard,et al.  The activation and regulation of fear and anxiety. , 1996, Nebraska Symposium on Motivation. Nebraska Symposium on Motivation.

[51]  S. Kosslyn,et al.  Neural effects of visualizing and perceiving aversive stimuli: a PET investigation. , 1996, Neuroreport.

[52]  E. Reiman,et al.  The application of positron emission tomography to the study of normal and pathologic emotions. , 1997, The Journal of clinical psychiatry.

[53]  Richard S. J. Frackowiak,et al.  Anatomy of motor learning. I. Frontal cortex and attention to action. , 1997, Journal of neurophysiology.

[54]  G. Fink,et al.  Neural activation during selective attention to subjective emotional responses , 1997, Neuroreport.

[55]  M. Bushnell,et al.  Pain affect encoded in human anterior cingulate but not somatosensory cortex. , 1997, Science.

[56]  Nathaniel M. Alpert,et al.  The functional neuroanatomy of anxiety: a study of three disorders using positron emission tomography and symptom provocation , 1997, Biological Psychiatry.

[57]  Karl J. Friston,et al.  Neuroanatomical correlates of externally and internally generated human emotion. , 1997, The American journal of psychiatry.

[58]  S. Rauch,et al.  Masked Presentations of Emotional Facial Expressions Modulate Amygdala Activity without Explicit Knowledge , 1998, The Journal of Neuroscience.

[59]  Karl J. Friston,et al.  Brain Systems Mediating Aversive Conditioning: an Event-Related fMRI Study , 1998, Neuron.