Jen-Chuen Hsieh

Central representation of chronic ongoing neuropathic pain studied by positron emission tomography.

&NA; This study was undertaken to explore whether the neural substrates demonstrated in brain imaging studies on experimentally induced pain are involved in the perception of chronic neuropathic pain. We investigated the cerebral representation of chronic lateralised ongoing pain in patients with painful mononeuropathy (PMN, i.e., pain in the distribution of a nerve, neuralgia) with positron emission tomography (PET), using regional cerebral blood flow (rCBF) as an index for neuronal activity. Eight patients (29–53 years) with PMN in the lower extremity (4 in the right, 4 in the left) were recruited. Paired comparisons of rCBF were made between the patients habitual pain (HP) state and the pain alleviated (PA) state following a successful regional nerve block (RNB) with lidocaine. The ongoing neuropathic pain resulted in activation of bilateral anterior insula, posterior parietal, lateral inferior prefrontal, and posterior cingulate cortices as well as the posterior sector of the right anterior cingulate cortex (ACC), Brodmann area (BA) 24, regardless of the side Of PMN. In addition, a reduction in rCBF was noted in the contralateral posterior thalamus. No significant change of rCBF was detected in the somatosensory areas, i.e., Sl and SII. The cerebral activation pattern, while addressing the differences between the HP and PA states, emphasises the affective‐motivational dimension in chronic ongoing neuropathic pain. The striking preferential activation of the right ACC (BA 24), regardless of the side of the PMN, not only confirms that the ACC participates in the sensorial/affectional aspect of the pain experience but also suggests a possible right hemispheric lateralisation of the ACC for affective processing in chronic ongoing neuropathic pain. Our data suggests that the brain employs different central mechanisms for chronic neuropathic pain and experimentally induced acute pain, respectively.

Traumatic nociceptive pain activates the hypothalamus and the periaqueductal gray: a positron emission tomography study

&NA; The study was conducted to investigate which areas of the brain respond to a painful encounter of minor dermal injury (a model of clinical pain)_elicited by intracutaneous injection of a minute amount of ethanol. Four healthy volunteers (27–46 years) were subjected to positron emission tomographic (PET) investigation of regional cerebral blood flow (rCBF), using [15O]butanol as tracer. The ethanol (20 &mgr;l, 70%) and saline (20 &mgr;l, 0.9%) were injected intracutaneously 3 times in a single‐blinded, semi‐randomised manner for the pain experiment. All the injections were performed, adjacent to each other, at the lateral aspect of the right upper arm. Subjective sensory intensity of pain, unpleasantness and anxiety were rated with separate 100‐mm visual analogue scales together with the Spielbergers State Anxiety Inventory (Spielberger et al. 1970) and heart rate. Paired‐subtraction (pixel‐by‐pixel) between ethanol and saline was performed. Traumatic pain significantly caused higher ratings of intensity and affect scales, i.e., pain intensity, unpleasantness and increased sympathetic activity (evidenced by tachycardia). In contrast the anxiety rating remained unchanged. Acute traumatic nociceptive pain prominently activated the hypothalamus and periaqueductal gray (PAG). In addition, activations of the prefrontal cortex (PFC), insular, anterior cingulate cortex (ACC), posterior parietal cortex (PPC), primary motor/somatosensory areas (MI/SI: face, upper arm), supplementary motor area (SMA), and cerebellum were also demonstrated. The central processing of the pain‐relevant/anticipatory arousal also engaged the PAG. This study demonstrates the involvement of the human cerebral cortex in perception, arousal, cognitive evaluative processes, and, hence, affective reactions (somatic/ autonomic outflow) associated with pain. The pain stimulus of traumatic character may, by its very nature, evoke the central processing to involve both the hypothalamus and the PAG.

Anticipatory coping of pain expressed in the human anterior cingulate cortex: a positron emission tomography study.

We used positron emission tomography (PET) to monitor the regional cerebral blood flow (rCBF) as an index of brain activity in regions proposed to participate in affective-motivational and cognitive-evaluative dimensions of pain during anticipation of a noxious stimulation. Specifically we were interested in the anterior cingulate cortex (ACC), the ventromedial prefrontal cortex (VMPFC) and the periaqueductal grey (PAG). Anticipating an unpredictable and unlearned pain stimulus activated the right ACC, the VMPFC and the PAG while anticipating a learned pain-stimulus resulted in a decreased activity in the ACC and the VMPFC. These patterns are compatible with two facets of affect-laden cognitive coping: alertness and attention-distraction. The right-preponderant expression of the changes in the ACC supports the hypothesis of a preferential role of the non-dominant hemisphere in negative emotional processing. The data demonstrate an anticipatory coping mechanism and illustrate a neurophysiological process underlying the modulation of attention to pain.

Activation of the hypothalamus characterizes the acupuncture stimulation at the analgesic point in human: a positron emission tomography study.

We performed a positron emission tomography study, using regional cerebral blood flow as the index of brain activity, to address the specificity of brain activation pattern by acupuncture stimulation of short duration at the classical analgesic point. Needling manipulation at 2 Hz was performed at a classical point of prominent analgesic efficacy (Li 4, Heku) and a near-by non-classical/non-analgesic point, respectively, in normal subjects. Regions activated by acupuncture stimulation at Li 4 included the hypothalamus with an extension to midbrain, the insula, the anterior cingulate cortex, and the cerebellum. Of note, it was only the stimulation at Li 4 that activated the hypothalamus under the similar psychophysical ratings of acupuncture sensation (deqi) as elicited by the stimulation at the two points, respectively. The data suggested that the hypothalamus might characterize the central expression of acupuncture stimulation at the classical analgesic point and serve as one key element in mediating analgesic efficacy of acupuncture stimulation.

Right-lateralised central processing for pain of nitroglycer-induced cluster headache

&NA; Recent functional brain imaging studies with positron emission tomography (PET) suggest a preference of the right hemisphere, especially the anterior cingulate cortex (ACC), in affective processing of the clinical pain syndromes. We have investigated the central processing of cluster headache (CH) attacks provoked by sublingual nitroglycerin (NTG). In the cerebrum, provoked CH activated the ACC and the temporopolar region of the right hemisphere in addition to other regions. The regions activated in the ACC (Brodmann area (BA) 24 and 32) are involved in affective/cognitive processing of pain and willed attention. Our study discloses the preferential role of the right hemisphere in attributing emotional valence and attention to the suffering of pain. The findings support the theory of a right hemispheric specialisation in the mediation of withdrawal‐related negative affect. The divergence of the distributed central processing between provoked cluster headache attack and experimentally induced acute pain indicates different central mechanisms for different types of pain.

Structural and cognitive deficits in remitting and non-remitting recurrent depression: A voxel-based morphometric study

Remission is the optimal outcome for major depressive disorder (MDD), but many patients do not improve appreciably despite treatment with medication. Treatment-resistant patients may experience deterioration in cognitive functions. Research has reported structural abnormalities in certain brain areas that may contribute to a poor clinical response. We hypothesize that there will be structural differences between patients able to achieve remission and those responding poorly to antidepressants. In the first voxel-based morphometric (VBM) study comparing remitting with non-remitting MDD, we investigated gray matter volume (GMV) differences between depressives to determine which structural abnormalities existed, and correlated these with diminished cognitive functioning. Of 44 adults with recurrent MDD, 19 had full remissions and 25 were non-remitters after a 6-week trial with antidepressant treatment. Remission was defined by 17-item Hamilton Depression Rating Scale scores of </=7 for at least 2 weeks. VBM and neuropsychological studies were conducted on all patients and 25 healthy controls. The patients who remitted revealed milder visual attention deficits than did controls. This correlated with reduced GMV in the left postcentral gyrus (Brodmann area, or BA, 3) and the bilateral medial/superior frontal gyrus (BA 6). The non-remitting patients had reduced GMV in the left dorsolateral prefrontal cortex (DLPFC, BA 9), and impaired acoustic and visual attention associated with GMV differences in several cortical regions, thalamus and amygdala/parahippocampal gyrus. These findings indicated that patients whose MDD remitted were cognitively and morphologically different from non-remitters. Voxel-based structural deficits in the left DLPFC may characterize a subgroup of people with recurrent MDD who respond poorly to antidepressants.

Orthographic and phonological processing of Chinese characters: an fMRI study

The present study used functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms underlying the orthographic and phonological processing of Chinese characters. Four tasks were devised, including one homophone judgment and three physical judgments of characters, pseudo-characters, and Korean-like nonsense figures. While the left occipitotemporal region, left dorsal processing stream, and right middle frontal gyrus constitute a network for orthographic processing, the left premotor gyrus, left middle/inferior frontal gyrus, supplementary motor area (SMA), and the left temporoparietal region work in concert for phonological processing. The ventral part of the left inferior frontal cortex responds specifically to the character stimuli, suggesting a general lexical processing role for this region for linguistic material. The stronger activation of the dorsal visual stream by Chinese homophone judgment pinpoints a tight coupling between phonological representation of Chinese characters and corresponding orthographic percepts. The concomitant engagement of sets of regions for different levels of Chinese orthographic and phonological processing is consistent with the notion of distributed parallel processing.

Coexistence of attention-based facilitation and inhibition in the human cortex

A key function of attention is to select an appropriate subset of available information by facilitation of attended processes and/or inhibition of irrelevant processing. Functional imaging studies, using positron emission tomography, have during different experimental tasks revealed decreased neuronal activity in areas that process input from unattended sensory modalities. It has been hypothesized that these decreases reflect a selective inhibitory modulation of nonrelevant cortical processing. In this study we addressed this question using a continuous arithmetical task with and without concomitant disturbing auditory input (task-irrelevant speech). During the arithmetical task, irrelevant speech did not affect task-performance but yielded decreased activity in the auditory and midcingulate cortices and increased activity in the left posterior parietal cortex. This pattern of modulation is consistent with a top down inhibitory modulation of a nonattended input to the auditory cortex and a coexisting, attention-based facilitation of task-relevant processing in higher order cortices. These findings suggest that task-related decreases in cortical activity may be of functional importance in the understanding of both attentional mechanisms and task-related information processing.

Brain morphological changes associated with cyclic menstrual pain

&NA; Primary dysmenorrhea (PDM) is the most prevalent gynecological disorder for women in the reproductive age. PDM patients suffer from lower abdominal pain that starts with the onset of the menstrual flow. Prolonged nociceptive input to the central nervous system can induce functional and structural alterations throughout the nervous system. In PDM, a chronic viscero‐nociceptive drive of cyclic nature, indications of central sensitization and altered brain metabolism suggest a substantial central reorganization. Previously, we hypothesized that disinhibition of orbitofrontal networks could be responsible for increased pain and negative affect in PDM. Here, we further tested this hypothesis. We used an optimized voxel‐based morphometry (VBM) approach to compare total and regional gray matter (GM) increases and decreases in 32 PDM patients with 32 healthy age and menstrual cycle matched (peri‐ovulatory phase) controls. Abnormal decreases were found in regions involved in pain transmission, higher level sensory processing, and affect regulation while increases were found in regions involved in pain modulation and in regulation of endocrine function. Moreover, GM changes in regions involved in top‐down pain modulation and in generation of negative affect were related to the severity of the experienced PDM pain. Our results demonstrate that abnormal GM volume changes are present in PDM patients even in the absence of pain. These changes may underpin a combination of impaired pain inhibition, increased pain facilitation and increased affect. Our findings highlight that longer lasting central changes may occur not only in sustained chronic pain conditions but also in cyclic occurring pain conditions.

Frequency effects of Chinese character processing in the brain: an event-related fMRI study.

Knowing how the brain processes Chinese characters of different frequencies of occurrence may shed light on the extent to which orthographic variations of different languages can influence reading processes in the brain. In the present study, event-related fMRI was used to investigate frequency effects on Chinese character processing. Reading low-frequency characters invoked higher activation in several brain regions including the left premotor/inferior frontal gyrus, supplementary motor area, left anterior insula, left posterior inferior temporal gyrus, left superior parietal cortex, and lingual cortex, while reading high-frequency characters resulted in higher activation in the left supramarginal/angular gyrus and left precuneus. The activation pattern of reading infrequently encountered characters reflects a more demanding processing procedure of retrieving, formulating, and coordinating the phonological output. Access to the lexical route may benefit the reading of high-frequency characters. By uncovering the differential brain responses in reading Chinese characters of different occurrence frequencies, not only has a substantial overlap between functional neuroanatomy of reading Chinese and alphabetical languages been demonstrated, but also features permitting the separation of language-specific content from universal mechanisms.