The causes underlying phantom limb pain are still unknown. Recent studies on the consequences of nervous system damage in animals and humans reported substantial reorganization of primary somatosensory cortex subsequent to amputation, and one study showed that cortical reorganization is positively correlated with phantom limb pain. This paper examined the hypothesis of a functional relationship between cortical reorganization and phantom limb pain. Neuroelectric source imaging was used to determine changes in cortical reorganization in somatosensory cortex after anesthesia of an amputation stump produced by brachial plexus blockade in six phantom limb pain patients and four pain-free amputees. Three of six phantom limb subjects experienced a virtual elimination of current phantom pain attributable to anesthesia (mean change: 3.8 on an 11-point scale; Z ϭ Ϫ1.83; p Ͻ 0.05) that was mirrored by a very rapid elimination of cortical reorganization in somatosensory cortex (change ϭ 19.8 mm; t (2) ϭ 5.60; p Ͻ 0.05). Cortical reorganization remained unchanged (mean change ϭ 1.6 mm) in three phantom limb pain amputees whose pain was not reduced by brachial plexus blockade and in the phantom painfree amputation controls. These findings suggest that cortical reorganization and phantom limb pain might have a causal relationship. Methods designed to alter cortical reorganization should be examined for their efficacy in the treatment of phantom limb pain.

Phantom limb pain (PLP) in amputees is associated with reorganizational changes in the somatosensory system. To investigate the relationship between somatosensory and motor reorganization and phantom limb pain, we used focal transcranial magnetic stimulation (TMS) of the motor cortex and neuroelectric source imaging of the somatosensory cortex (SI) in patients with and without phantom limb pain. For transcranial magnetic stimulation, recordings were made bilaterally from the biceps brachii, zygomaticus, and depressor labii inferioris muscles. Neuroelectric source imaging of the EEG was obtained after somatosensory stimulation of the skin overlying face and hand. Patients with phantom limb pain had larger motor-evoked potentials from the biceps brachii, and the map of outputs was larger for muscles on the amputated side compared with the intact side. The optimal scalp positions for stimulation of the zygomaticus and depressor labii inferioris muscles were displaced significantly more medially (toward the missing hand representation) in patients with phantom limb pain only. Neuroelectric source imaging revealed a similar medial displacement of the dipole center for face stimulation in patients with phantom limb pain. There was a high correlation between the magnitude of the shift of the cortical representation of the mouth into the hand area in motor and somatosensory cortex and phantom limb pain. These results show enhanced plasticity in both the motor and somatosensory domains in amputees with phantom limb pain.

Lesion evidence indicates that words from different lexical categories, such as nouns and verbs, may have different cortical counterparts. In this study, processing of nouns and verbs was investigated in the intact brain using (i) behavioral measures, (ii) stimulus-triggered event-related potentials and (iii) high-frequency electrocortical responses in the gamma band. Nouns and verbs carefully matched for various variables, including word frequency, length, arousal and valence, were presented in a lexical decision task while electrocortical responses were recorded. In addition, information about cognitive processing of these stimuli was obtained using questionnaires and reaction times. As soon as approximately 200 ms after stimulus onset, event-related potentials disclosed electrocortical differences between nouns and verbs over widespread cortical areas. In a later time window, 500-800 ms after stimulus onset, there was a significant difference between high-frequency responses in the 30 Hz range. Difference maps obtained from both event-related potentials and high-frequency responses revealed strong between-category differences of signals recorded above motor and visual cortices. Behavioral data suggest that these different physiological responses are related to semantic associations (motor or visual) elicited by these word groups. Our results are consistent with a neurobiological model of language representation postulating cell assemblies with distinct cortical topographies as biological counterparts of words. Assemblies representing nouns referring to visually perceived objects may include neurons in visual cortices, and assemblies representing action verbs may include additional neurons in motor, premotor and prefrontal cortices. Event-related potentials and high-frequency responses are proposed to indicate two different functional states of cell assemblies: initial full activation ('ignition') and continuous reverberatory activity.

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Animal studies have shown that the brain is an insulin-responsive organ and that central nervous insulin resistance induces obesity and disturbances in glucose metabolism. In humans, insulin effects in the brain are poorly characterized. We used a magnetoencephalography approach during a two-step hyperinsulinemic euglycemic clamp to (i) assess cerebrocortical insulin effects in humans, (ii) compare these effects between 10 lean and 15 obese subjects, and (iii) test whether the insulin receptor substrate (IRS)-1 Gly972Arg polymorphism in the insulin-signaling cascade modifies these effects. Both spontaneous and stimulated (mismatch negativity) cortical activity were assessed. In lean humans, stimulated cortical activity (P ‫؍‬ 0.046) and the beta and theta band of spontaneous cortical activity (P ‫؍‬ 0.01 and 0.04) increased with insulin infusion relative to saline. In obese humans, these effects were suppressed. Moreover, the insulin effect on spontaneous cortical activity correlated negatively with body mass index and percent body fat (all r < ؊0.4; all P < 0.05) and positively with insulin sensitivity of glucose disposal (theta band, r ‫؍‬ 0.48, P ‫؍‬ 0.017). Furthermore, insulin increased spontaneous cortical activity (beta band) in carriers of wild-type IRS-1, whereas, in carriers of the 972Arg allele, this insulin effect was absent (P ‫؍‬ 0.01). We conclude that, in lean humans, insulin modulates cerebrocortical activity, and that these effects are diminished in obese individuals. Moreover, cerebrocortical insulin resistance is found in individuals with the Gly972Arg polymorphism in IRS-1, which is considered a type 2 diabetes risk gene.glucose metabolism ͉ insulin resistance ͉ magnetoencephalography ͉ mismatch negativity ͉ type 2 diabetes T he human brain has been traditionally regarded as an insulininsensitive organ. However, there is now growing evidence that insulin signaling might be an important modulator of several functions of the brain. The insulin receptor and other components of the insulin-signaling chain, such as the insulin receptor substrate (IRS)-1 are ubiquitously expressed throughout the brain in animals and humans with particularly high concentrations in the hypothalamus, the hippocampus, and the cerebral cortex (1-3). Early work in animals suggested that insulin acts in the CNS and controls food intake and body weight (4). Furthermore, it was clearly shown that insulin crosses the blood-brain barrier (5) and, when given directly to the brain, suppresses food intake (6, 7) and mediates peripheral metabolic effects (8). Most important for the understanding of central nervous insulin function was the observation that brainspecific deletion of the insulin receptor in mice resulted in hyperphagia, obesity, and metabolic insulin resistance (9).In mice, insulin effects have been intensively studied in the hypothalamus. However, it is noteworthy that insulin receptors are also abundant in the cerebral cortex (2). Furthermore, intracerebroventricular insulin administration was associated with imp...

These data support the hypothesis that patients with panic disorder are characterized by greater activation of a right frontal avoidance-withdrawal system in negatively valenced situations. The findings are interpreted as biological evidence for a disturbed cortical processing in patients with panic disorder.

We explored classical conditioning in human subjects who had lesions in their cerebellar circuitry. Seven patients with damage to cerebellar structures and matched control subjects underwent simple delay tone-airpuff conditioning. Eyelid conditioned response (CR) acquisition was severely disrupted in the patient group, whereas autonomic CRs and slow cortical potentials developing between conditioned stimulus (CS) and the unconditioned stimulus (UCS) were unaffected. Results are consistent with animal studies and earlier case reports indicating that intact cerebellar structures are necessary for the acquisition of classically conditioned motor responses.

The representation of visual objects in short-term memory has been shown to be related to increased gamma-band activity in the electroencephalogram. Using a similar paradigm, we investigated oscillatory magnetoencephalographic activity in human subjects during a delayed matching-to-sample task requiring working memory of auditory spatial information. The memory task involved same-different judgments about the lateralization angle of pairs of filtered noise stimuli (S1 and S2) separated by 800 msec delays of background noise. This was compared with a control condition requiring the detection of a possible change in the background noise volume appearing instead of S2 (volume task). Statistical probability mapping revealed increased spectral activity at 59 Hz over left parietal cortex during the delay phase of the memory condition. In addition, 59 Hz coherence was enhanced between left parietal and right frontal sensors. During the end of the delay and during the presentation of S2, enhanced gamma-band activity at 67 Hz was observed over right frontal and later over midline parietal areas. In contrast, the volume task was characterized by increased left inferior frontotemporal 59 Hz spectral amplitude after S1. Apparently representation of the spatial position of a sound source is associated both with synchronization of networks in parietal areas involved in the auditory dorsal stream and with increased coupling between networks serving representation of audiospatial information and frontal executive systems. The comparison with S2 seemed to activate frontal and parietal neuronal ensembles. Gamma-band activity during the volume task may reflect auditory pattern encoding in auditory ventral stream areas.