Wolfgang H. R. Miltner

Treatment-Induced Cortical Reorganization After Stroke in Humans

BACKGROUND AND PURPOSE Injury-induced cortical reorganization is a widely recognized phenomenon. In contrast, there is almost no information on treatment-induced plastic changes in the human brain. The aim of the present study was to evaluate reorganization in the motor cortex of stroke patients that was induced with an efficacious rehabilitation treatment. METHODS We used focal transcranial magnetic stimulation to map the cortical motor output area of a hand muscle on both sides in 13 stroke patients in the chronic stage of their illness before and after a 12-day-period of constraint-induced movement therapy. RESULTS Before treatment, the cortical representation area of the affected hand muscle was significantly smaller than the contralateral side. After treatment, the muscle output area size in the affected hemisphere was significantly enlarged, corresponding to a greatly improved motor performance of the paretic limb. Shifts of the center of the output map in the affected hemisphere suggested the recruitment of adjacent brain areas. In follow-up examinations up to 6 months after treatment, motor performance remained at a high level, whereas the cortical area sizes in the 2 hemispheres became almost identical, representing a return of the balance of excitability between the 2 hemispheres toward a normal condition. CONCLUSIONS This is the first demonstration in humans of a long-term alteration in brain function associated with a therapy-induced improvement in the rehabilitation of movement after neurological injury.

Event-related brain potentials following incorrect feedback in a time-estimation task: Evidence for a “generic” neural system for error detection

We examined scalp-recorded event-related potentials following feedback stimuli in a time-estimation task. Six hundred msec after indicating the end of a 1 sec interval, subjects received a visual, auditory, or somatosensory stimulus that indicated whether the interval they had produced was correct. Following feedback indicating incorrect performance, a negative deflection occurred, whose characteristics corresponded closely to those of the component (the error-related negativity) that accompanies errors in choice reaction time tasks. Furthermore, equivalent dipole analysis suggested that, for all three modalities, the distribution of the scalp potential was consistent with a local source in the anterior cingulate cortex or a more distributed source in the supplementary motor areas. These loci correspond closely to those described previously for the error-related negativity. We conclude that the error-related negativity is the manifestation of the activity of a generic neural system involved in error detection.

Coherence of gamma-band EEG activity as a basis for associative learning.

Different regions of the brain must communicate with each other to provide the basis for the integration of sensory information, sensory-motor coordination and many other functions that are critical for learning, memory, information processing, perception and the behaviour of organisms. Hebb suggested that this is accomplished by the formation of assemblies of cells whose synaptic linkages are strengthened whenever the cells are activated or ‘ignited’ synchronously. Hebbs seminal concept has intrigued investigators since its formulation, but the technology to demonstrate its existence had been lacking until the past decade. Previous studies have shown that very fast electroencephalographic activity in the gamma band (20–70 Hz) increases during, and may be involved in, the formation of percepts and memory, linguistic processing, and other behavioural and preceptual functions. We show here that increased gamma-band activity is also involved in associative learning. In addition, we find that another measure, gamma-band coherence, increases between regions of the brain that receive the two classes of stimuli involved in an associative-learning procedure in humans. An increase in coherence could fulfil the criteria required for the formation of hebbian cell assemblies, binding together parts of the brain that must communicate with one another in order for associative learning to take place. In this way, coherence may be a signature for this and other types of learning.

Motor cortex plasticity during constraint-induced movement therapy in stroke patients

Stroke patients in the chronic phase received constraint-induced (CI) movement therapy. The motor cortex was spatially mapped using focal transcranial magnetic stimulation (TMS) before and after 2 weeks of treatment. Motor-output areas of the abductor pollicis brevis muscle, motor evoked potential (MEP) amplitudes and location of centre of gravity (CoG) of motor cortex output were studied. After CI therapy, motor performance improved substantially in all patients. There was also an increase of motor output area size and MEP amplitudes, indicating enhanced neuronal excitability in the damaged hemisphere for the target muscles. The mean centre of gravity of the motor output maps was shifted considerably after the rehabilitation, indicating the recruitment of motor areas adjacent to the original location. Thus, even in chronic stroke patients, reduced motor cortex representations of an affected body part can be enlarged and increased in level of excitability by an effective rehabilitation procedure. The data therefore demonstrate a CNS correlate of therapy-induced recovery of function after nervous system damage in humans.

Waiting for spiders: Brain activation during anticipatory anxiety in spider phobics

Anticipatory anxiety during expectation of phobogenic stimuli is an integral part of abnormal behaviour in phobics. The neural basis of anticipatory anxiety in specific phobia is unknown. Using functional magnetic resonance imaging (fMRI), we explored brain activation in subjects with spider phobia and in non-phobic subjects, while participants anticipated the presentation of either neutral or phobogenic visual stimuli. Subjective ratings indicated that anticipation of phobia-related stimuli was associated with increased anxiety in phobics but not in healthy subjects. FMRI results showed increased activation of the dorsal anterior cingulate cortex (ACC), insula, thalamus, and visual areas in phobics compared to controls during anticipation of phobia-relevant versus anticipation of neutral stimulation. Furthermore, for this contrast, we found also increased activation of the bed nucleus of the stria terminalis (BNST). This particular finding supports models, which propose, based on animal experiments, a critical involvement of the BNST in anticipatory anxiety. Finally, correlation analysis revealed that subjective anxiety of phobics correlated significantly with activation in rostral and dorsal ACC and the anterior medial prefrontal cortex. Thus, activation in different ACC regions and the medial prefrontal cortex seems to be specifically associated with the severity of experienced anticipatory anxiety in subjects with spider phobia.

Effects of cognitive-behavioral therapy on brain activation in specific phobia

Little is known about the effects of successful psychotherapy on brain function in subjects with anxiety disorders. The present study aimed to identify changes in brain activation following cognitive-behavioral therapy (CBT) in subjects suffering from specific phobia. Using functional magnetic resonance imaging (fMRI), brain activation to spider videos was measured in 28 spider phobic and 14 healthy control subjects. Phobics were randomly assigned to a therapy-group (TG) and a waiting-list control group (WG). Both groups of phobics were scanned twice. Between scanning sessions, CBT was given to the TG. Before therapy, brain activation did not differ between both groups of phobics. As compared to control subjects, phobics showed greater responses to spider vs. control videos in the insula and anterior cingulate cortex (ACC). CBT strongly reduced phobic symptoms in the TG while the WG remained behaviorally unchanged. In the second scanning session, a significant reduction of hyperactivity in the insula and ACC was found in the TG compared to the WG. These results propose that increased activation in the insula and ACC is associated with specific phobia, whereas an attenuation of these brain responses correlates with successful therapeutic intervention.

Psychobiology of altered states of Consciousness

The article reviews the current knowledge regarding altered states of consciousness (ASC) (a) occurring spontaneously, (b) evoked by physical and physiological stimulation, (c) induced by psychological means, and (d) caused by diseases. The emphasis is laid on psychological and neurobiological approaches. The phenomenological analysis of the multiple ASC resulted in 4 dimensions by which they can be characterized: activation, awareness span, self-awareness, and sensory dynamics. The neurophysiological approach revealed that the different states of consciousness are mainly brought about by a compromised brain structure, transient changes in brain dynamics (disconnectivity), and neurochemical and metabolic processes. Besides these severe alterations, environmental stimuli, mental practices, and techniques of self-control can also temporarily alter brain functioning and conscious experience.

Implementation of error-processing in the human anterior cingulate cortex: a source analysis of the magnetic equivalent of the error-related negativity

Recent research has described a component of human electrical brain activity (the ERN or NE) that is associated with error-processing. In the present experiment, we used magneto-encephalographic recordings to provide converging evidence both for the existence of this component and for its putative source in the brain. Six human subjects performed a Go-NoGo task while both magnetoencephalographic and electroencephalographic brain activity were recorded. We found evidence for a magnetic equivalent of the ERN and dipole source analysis suggested that this activity was generated in the anterior cingulate cortex. These data converge with those from electrical recordings in implicating this brain structure in error-processing.

Brain activation to phobia-related pictures in spider phobic humans: an event-related functional magnetic resonance imaging study

Using event-related functional magnetic resonance imaging we investigated blood oxygen level dependent brain activation in spider phobic and non-phobic subjects while exposed to phobia-related pictures (spiders) and non-phobia-related pictures (snakes and mushrooms). In contrast to previous studies, we show significantly increased amygdala activation in spider phobics, but not in controls, during presentation of phobia-relevant visual stimuli. Furthermore, phobia-specific increased activation was also found in the insula, the orbitofrontal cortex and the uncus. Our study confirms the role of the amygdala in fear processing and provides insights into brain activation patterns when animal phobics are confronted with phobia-related stimuli.

Common and distinct brain activation to threat and safety signals in social phobia

Background: Little is known about the functional neuroanatomy underlying the processing of emotional stimuli in social phobia. Objectives: To investigate specific brain activation that is associated with the processing of threat and safety signals in social phobics. Methods: Using functional magnetic resonance imaging, brain activation was measured in social phobic and nonphobic subjects during the presentation of angry, happy and neutral facial expressions under free viewing conditions. Results: Compared to controls, phobics showed increased activation of extrastriate visual cortex regardless of facial expression. Angry, but not neutral or happy, faces elicited greater insula responses in phobics. In contrast, both angry and happy faces led to increased amygdala activation in phobics. Conclusions: The results support the hypothesis that the amygdala is involved in the processing of negative and positive stimuli. Furthermore, social phobics respond sensitively not only to threatening but also to accepting faces and common and distinct neural mechanisms appear to be associated with the processing of threat versus safety signals.