Suppression of visual perception by magnetic coil stimulation of human occipital cortex

Magnetic coil (MC) stimulation percutaneously of human occipital cortex was tested on perception of 3 briefly presented, randomly generated alphabetical characters. When the visual stimulus-MC pulse interval was less than 40-60 msec, or more than 120-140 msec, letters were correctly reported; at test intervals of 80-100 msec, a blur or nothing was seen. Shifting the MC location in the transverse and rostro-caudal axes had effects consistent with the topographical representation in visual cortex, but incompatible with an effect on attention or suppression from an eyeblink. The MC pulse probably acts by eliciting IPSPs in visual cortex. The neural activity subserving letter recognition is probably transmitted from visual cortex within 140 msec of the visual stimulus.     

Somatotopy and temporal dynamics of sensorimotor interactions: evidence from double afferent inhibition

Moving and interacting with the world requires that the sensory and motor systems share information, but while some information about tactile events is preserved during sensorimotor transfer the spatial specificity of this information is unknown. Afferent inhibition (AI) studies, in which corticospinal excitability (CSE) is inhibited when a single tactile stimulus is presented before a transcranial magnetic stimulation pulse over the motor cortex, offer contradictory results regarding the sensory‐to‐motor transfer of spatial information. Here, we combined the techniques of AI and tactile repetition suppression (the decreased neurophysiological response following double stimulation of the same vs. different fingers) to investigate whether topographic information is preserved in the sensory‐to‐motor transfer in humans. We developed a double AI paradigm to examine both spatial (same vs. different finger) and temporal (short vs. long delay) aspects of sensorimotor interactions. Two consecutive electrocutaneous stimuli (separated by either 30 or 125 ms) were delivered to either the same or different fingers on the left hand (i.e. index finger stimulated twice or middle finger stimulated before index finger). Information about which fingers were stimulated was reflected in the size of the motor responses in a time‐constrained manner: CSE was modulated differently by same and different finger stimulation only when the two stimuli were separated by the short delay (P = 0.004). We demonstrate that the well‐known response of the somatosensory cortices following repetitive stimulation is mirrored in the motor cortex and that CSE is modulated as a function of the temporal and spatial relationship between afferent stimuli.     

Two means of suppressing visual awareness: a direct comparison of visual masking and transcranial magnetic stimulation

Visual masking and visual suppression by transcranial magnetic stimulation (TMS) are both widely utilized in cognitive neuroscience to investigate a wide range of processes. However, the neural processes affected by visual masking and TMS remain unclear. We compared para- and metacontrast masking with TMS-induced suppression of visibility in a within-subjects design where participants were asked to detect and rate the visibility of a stimulus. TMS pulses applied 75-109 msec after the onset of the visual stimulus reduced the subjective visibility of the target. Even when the TMS pulses completely eliminated the conscious perception of the target, unconscious location detection was possible. The visual masking condition yielded similar results: metacontrast did not eliminate unconscious location detection even when the target was reported not seen at all. As the first target-related signals were likely to reach the visual cortex before TMS pulses started to modulate target visibility, we suggest that TMS and metacontrast masking affected neural signals subsequent to the target's transient onset-response. This implies that a preserved onset-response is sufficient for unconscious processing of stimulus attributes, but not for conscious perception.     

Sensory perception changes induced by transcranial magnetic stimulation over the primary somatosensory cortex in Parkinson's disease

Sensory symptoms are common nonmotor manifestations of Parkinson's disease. It has been hypothesized that abnormal central processing of sensory signals occurs in Parkinson's disease and is related to dopaminergic treatment. The objective of this study was to investigate the alterations in sensory perception induced by transcranial magnetic stimulation of the primary somatosensory cortex in patients with Parkinson's disease and the modulatory effects of dopaminergic treatment. Fourteen patients with Parkinson's disease with and without dopaminergic treatment and 13 control subjects were included. Twenty milliseconds after peripheral electrical tactile stimuli in the contralateral thumb, paired‐pulse transcranial magnetic stimulation over the right primary somatosensory cortex was delivered. We evaluated the perception of peripheral electrical tactile stimuli at 2 conditioning stimulus intensities, set at 70% and 90% of the right resting motor threshold, using different interstimulus intervals. At 70% of the resting motor threshold, paired‐pulse transcranial magnetic stimulation over the right primary somatosensory cortex induced an increase in positive responses at short interstimulus intervals (1–7 ms) in controls but not in patients with dopaminergic treatment. At 90% of the resting motor threshold, controls and patients showed similar transcranial magnetic stimulation effects. Changes in peripheral electrical tactile stimuli perception after paired‐pulse transcranial magnetic stimulation over the primary somatosensory cortex are altered in patients with Parkinson's disease with dopaminergic treatment compared with controls. These findings suggest that primary somatosensory cortex excitability could be involved in changes in somatosensory integration in Parkinson's disease with dopaminergic treatment. © 2011 Movement Disorder Society     

Delayed facilitation of motor cortical excitability following repetitive finger movements.

OBJECTIVES: To define motor cortical excitability changes occurring at various times after non-fatiguing bimanual exercise of the index fingers. METHODS: Twenty healthy right-handed subjects were studied with transcranial magnetic stimulation (TMS) of the right non-dominant hemisphere. They performed regular (3-4/s) repetitive opening-closing bilateral movements of the index finger onto the thumb. Motor evoked potentials (MEPs) of the left first dorsal interosseus (FDI) and rate of the repetitive finger movements were determined (1) before exercise, (2) immediately following 3 exercise periods of 30, 60 and 90 s, and (3) over a subsequent 30 min rest period. RESULTS: Rate of movement did not show significant change during any of the exercise periods but did increase significantly when tested after 15 min of rest. MEPs immediately after 30 and 60 s of exercise were facilitated whereas MEPs after 90 s of exercise did not differ from baseline measures. MEP amplitudes were significantly increased after rest of approximately 15 min compared to the baseline MEPs. In contrast, motor potentials evoked by peripheral nerve stimulation were unchanged throughout the experimental test periods. CONCLUSIONS: Motor cortical excitability relating to an intrinsic finger muscle (FDI) was facilitated beginning 15 min after a brief period of non-forceful, repetitive activity of that muscle. This delayed facilitation of motor cortex after exercise may represent a form of short-term potentiation of motor cortical excitability.     

Changes in excitability of motor cortical circuitry in patients with parkinson's disease

Using the technique of transcranial magnetic stimulation over the motor areas of cortex and recording electromyographic (EMG) responses from the first dorsal interosseous muscle, we measured the excitability of corticocortical inhibitory circuits at rest using a double pulse paradigm, in 11 patients with Parkinson's disease (PD) studied both on (ON) and off (OFF) (after overnight withdrawal) their normal medication and in 10 age-matched control subjects. There was a significant decrease in the amount of corticocortical inhibition at short (1–5 msec) interstimulus intervals in patients relative to their controls, which improved after L -dopa intake. For comparison with previous reports using transcranial magnetic stimulation we also measured the duration of the EMG silent period when stimuli were given to voluntarily active muscle, and the threshold for evoking an EMG response in both the active and relaxed states. There was no change in the threshold for evoking EMG responses whether muscles were active or relaxed. However, the silent period was significantly prolonged when ON compared with OFF, although in neither state was the duration significantly different from that seen in normals. We suggest that there may be abnormalities of motor cortical inhibitory mechanisms in patients with Parkinson's disease that are not readily detected using threshold or silent period measurements alone.     

Phantom digit somatotopy: a functional magnetic resonance imaging study in forearm amputees

Forearm amputees often experience non-painful sensations in their phantom when the amputation stump is touched. Cutaneous stimulation of specific stump areas may be perceived as stimulation of specific phantom fingers (stump hand map). The neuronal basis of referred phantom limb sensations is unknown. We used functional magnetic resonance imaging to demonstrate a somatotopic map of the phantom fingers in the hand region of the primary somatosensory cortex after tactile stump stimulation. The location and extent of phantom finger activation in the primary somatosensory cortex corresponded well to the location of normal fingers in a reference population. Stimulation of the stump hand map resulted in an increased bilateral activation of the primary somatosensory cortex compared with stimulation of forearm regions outside the stump hand map. Increased activation was also seen in contralateral posterior parietal cortex and premotor cortex. Ipsilateral primary somatosensory cortex activation might represent a compensatory mechanism and activation of the non-primary fronto-parietal areas might correspond to awareness of the phantom limb, which is enhanced when experiencing the referred sensations. It is concluded that phantom sensation elicited by stimulation of stump hand map areas is associated with activation of finger-specific somatotopical representations in the primary somatosensory cortex. This suggests that the primary somatosensory cortex could be a neural substrate of non-painful phantom sensations. The stump hand map phenomenon might be useful in the development of prosthetic hand devices.     

Suppression of visual perception by transcranial magnetic stimulation — experimental findings in healthy subjects and patients with optic neuritis

The influence of noninvasive magnetic brain stimulation by a magnetic coil (MC) placed over the occiput on perception and correct reporting of a briefly presented set of 3 letters of the alphabet was examined in 15 patients with prolonged VEP latencies due to neuritis of the optic nerve. The results derived from observing these patients were compared to the results obtained from an age-matched control group of 20 healthy voluntary subjects examined under the same experimental conditions. In both groups it was possible to demonstrate that transcranial magnetic stimulation is able to suppress recognition of the letters if applied with a certain delay time after a brief presentation of the visual stimulus. The groups were compared to each other with regard to the delay with which it was possible to demonstrate the most effective suppression. In the healthy subjects, this delay was found between 60 and 100 msec. In the patients, it was prolonged to 80–140 msec. This prolongation was closely related to the VEP latencvy (P100).Furthermore, visual suppression and the influence on it by different parameters were studied in detail in healthy subjects; the visual suppression depends on visual (e.g., brightness, duration) and magnetic (e.g., intensity) stimulus conditions.The method describes seems to be of considerable value in the investigation of basic mechanisms of visual perception. This includes pathophysiological changes caused by optic neuritis and possibly other disorders affecting the visual system.     

Silent period induced by cutaneous stimulation.

An electrical stimulus applied to a cutaneous nerve during isometric muscle contraction causes a suppression of EMG activity (silent period) followed by a rebound. The extent of inhibition is related to the stimulus intensity as the silent period is more evident when stimulation is perceived as painful. The silent period is present in different limb and cranial muscles after stimulation of the same cutaneous nerve and in the same muscle after stimulation of distant cutaneous nerves. It also occurs synchronously in antagonist muscles. Within the silent period induced after cutaneous stimulation the maximal inhibition on the opponens pollicis motor neuron pool, as tested by the motor response evoked after transcranial cortical stimulation, occurs between 50 and 70 msec. Using the double stimulus technique to study the recovery cycle, the silent period is present at interstimulus intervals as low as 100 msec, and does not habituate with trains of stimuli at frequencies up to 5 Hz. Our results suggest that motor neuron inhibition from nociceptive stimulation may be mediated by Renshaw cells directly activated by high threshold cutaneous afferents.     

Motor potentials evoked by magnetic stimulation of the motor cortex in normal subjects and patients with motor disorders.

Motor evoked potentials (MEPs) elicited by magnetic coil stimulation of motor cortex were studied at rest and during maximum voluntary muscle contraction in 20 normal subjects and 42 patients with motor disorders. MEP parameters employed in this study included: onset latency, amplitude, MEP/M wave amplitude ratio and background EMG/MEP area ratio. Maximum voluntary contraction increased the amplitude of MEPs compared to the size of M waves elicited by peripheral nerve stimulation. A reduced MEP/M wave amplitude ratio had a higher correlation with pyramidal tract involvement than did a prolonged MEP onset latency. Analysis of MEP parameters may help in the differential diagnosis of cerebral infarction, ALS and cervical spondylotic radiculomyelopathy. The inhibitory period which follows MEPs during voluntary contraction was observed in all subjects; the mean duration in normal subjects was 126.6 +/- 29.5 msec. The mean duration of the inhibitory period in patients with cerebral infarction, ALS and cervical spondylotic radiculomyelopathy was 73.9 +/- 41.7 msec, 79.5 +/- 54.5 msec and 85.1 +/- 36.5 msec, respectively. These values were significantly shorter than in normal subjects.     

Transcranial cortical stimulation. Late excitability changes in the soleus and anterior tibial motoneurone pools.

The effect of conditioning magnetic transcranial cortical stimulation (TCCS) on the excitability levels of the soleus and anterior tibial motoneurone pools was studied by Hmax/2 technique 40-400 msec after the stimulus. The target muscles were relaxed throughout the tests. Two periods of facilitation (the first at 80-100 msec and the second at 180-200 msec) were found. They shared approximately the same latencies as the late responses (S100 and S > 150) that we have previously recorded following TCCS. A period of inhibition that started at 150 msec was also recorded. A period of facilitation could also be noted when the conditioning stimulus was applied either over the deltoid muscle or when the click that accompanied the magnetic pulse was used. This suggests that brain-stem areas related to those of the startle reaction play an important role for the appearance of the facilitatory changes. The necessary input probably comes from both peripheral and cortical sources.     

Attention induces reciprocal activity in the human somatosensory cortex enhancing relevant- and suppressing irrelevant inputs from fingers.

OBJECTIVE: We studied whether attention regulates information processing in the human primary somatosensory cortex (SI) by selective enhancement of relevant- and suppression of irrelevant information. METHODS: Under successive and simultaneous electric stimuli to both the right index and middle fingers, tactile stimuli were randomly (20%) presented on one of the two fingers in separate two runs exchanging the finger. Subjects were requested to discriminate the tactile stimuli in an attention task to induce attention to one finger and to ignore the stimuli in a control task to avoid such an attention focus. Somatosensory evoked magnetic fields were measured only for the two-finger electric stimulation and an early component (M50) was analyzed. RESULTS: In spite of the two-finger simultaneous stimulation, attention to either the index or middle finger lowered or heightened the M50-sourse location, respectively. The attention task did not increase the M50 amplitude. CONCLUSIONS: Attention to a finger enhanced selectively the representation of the finger in the SI cortex. However, this SI activity did not increase the M50 amplitude, suggesting that the attention suppressed another finger region receiving the unattended inputs. SIGNIFICANCE: Attention regulates the SI activity by selectively enhancing the task-relevant information and by filtering out other noise inputs.     

Unconscious and conscious processing of color rely on activity in early visual cortex: a TMS study

Chromatic information is processed by the visual system both at an unconscious level and at a level that results in conscious perception of color. It remains unclear whether both conscious and unconscious processing of chromatic information depend on activity in the early visual cortex or whether unconscious chromatic processing can also rely on other neural mechanisms. In this study, the contribution of early visual cortex activity to conscious and unconscious chromatic processing was studied using single-pulse TMS in three time windows 40-100 msec after stimulus onset in three conditions: conscious color recognition, forced-choice discrimination of consciously invisible color, and unconscious color priming. We found that conscious perception and both measures of unconscious processing of chromatic information depended on activity in early visual cortex 70-100 msec after stimulus presentation. Unconscious forced-choice discrimination was above chance only when participants reported perceiving some stimulus features (but not color).     

Attenuation in detection of somatosensory stimuli by transcranial magnetic stimulation.

Effects of magnetic stimulation (MS) of the scalp and direct cortical electrical stimulation on detection of an electrical stimulus to the index finger (S1) were studied in 7 normal volunteers and a patient with epilepsy. Detection of somatosensory stimuli was attenuated when MS was delivered 200 msec before S1, was blocked when MS was delivered simultaneously to and 20 msec after S1, and was fully recovered when MS was delivered 200 msec after S1. This effect showed topographic specificity, being produced by scalp stimulation of restricted scalp positions contralateral to the finger stimulated, was maximal with low intensities of finger stimulation and high intensities of MS (usually over that required for motor threshold), and could also be produced in the absence of motor evoked responses in a peripheral hand muscle. These results show that a focal cortical stimulus can briefly attenuate detection of somatosensory stimuli before, during, and after cortical arrival of a somatosensory afferent volley. Several different mechanisms probably contribute to this phenomenon.     

Selective attention regulates spatial and intensity information processing in the human primary somatosensory cortex

Attention-related cognitive processes in the primary somatosensory cortex (SI) were studied by measuring somatosensory evoked magnetic fields (SEFs). Twenty-one normal adult human subjects participated in this study for investigating effects of attention and stimulus intensity on cortical finger representation in the SI cortex. Electric stimuli at low and high intensity were delivered to the index or middle finger in finger discrimination and non-discrimination task. For the low intensity stimulation at 1.25 times sensory threshold, an early component (M50) showed clear segregation of the sources for the two fingers and an increase of the amplitude specific to the finger discrimination task. Such an attentional effect on the SI cortex was masked by the high intensity stimulation (2.5 times sensory threshold); the M50 source separation by the fingers was induced irrespective of the discrimination or non-discrimination task. The results suggest that a conscious regulation of stimulus intensity coding in the SI cortex underlies the attention-dependent enhancement of spatial finger information processing.     

Relevance of stimulus duration for activation of motor and sensory fibers: implications for the study of H-reflexes and magnetic stimulation.

Electric stimuli with durations of 0.5-1.0 msec are optimal for studies of H-reflexes. It is more difficult to obtain H-reflexes with shorter duration stimuli or with magnetic stimulation. In order to understand this behavior, we studied the excitation thresholds for motor and sensory fibers in the ulnar, median and tibial nerves using both electric and magnetic stimulation. For short duration electrical stimuli (0.1 msec) the threshold for motor fibers is lower than for sensory fibers. For longer duration electric stimuli (1.0 msec) the threshold for sensory fibers is lower. For magnetic stimulation the threshold for motor fibers is much lower than for sensory fibers. Thus, stimulus duration is a critical parameter for sensory fiber excitation, and current magnetic stimulators are not optimal.     

An exteroceptive reflex in the sternocleidomastoid muscle produced by electrical stimulation of the supraorbital nerve in normal subjects and patients with spasmodic torticollis

We examined suppression of EMG activity in the contracting sternocleidomastoid muscles, produced by electrical stimulation of the supraorbital nerve in 10 normal subjects and 9 patients with spasmodic torticollis. This exteroceptive reflex in the sternocleidomastoid muscle consisted of 2 or 3 phases: (1) an early, small, and unstable phase of facilitation, followed by (2) a period of suppression beginning 35 msec after the stimulus, lasting for 35 msec with a reduction in EMG activity to approximately 40% of the prestimulus level, and (3) a further phase of facilitation at a latency of 70 msec, with duration 35 msec and an increase in EMG activity to approximately 35% above prestimulus levels. The latency and duration of the suppressive phase of this reflex were similar to the exteroceptive suppression of EMG activity in the masseter muscle after supraorbital nerve stimulation (masseter silent period). In patients with spasmodic torticollis, the depth of this exteroceptive suppression in the sternocleidomastoid muscles was less than that observed in an age-matched cohort of normal subjects, although the latency and duration were normal. In contrast, exteroceptive suppression in the masseter muscle was normal. These findings suggest abnormal function of inhibitory interneuronal networks between the 5th cranial nerve and the motor neurons of the spinal accessory and upper cervical nerves which mediate exteroceptive suppression in the sternocleidomastoid muscle in patients with spasmodic torticollis.     

Stimulation of the lateral habenula inhibits dopamine-containing neurons in the substantia nigra and ventral tegmental area of the rat

Neurons in the lateral habenula (LHb) of rats have efferent projections that terminate in the substantia nigra pars compacta (SNC) and ventral tegmental area (VTA), where cell bodies of dopamine-containing neurons are located. In order to study the influence of the habenula on dopaminergic activity, single-cell electrophysiological techniques were used to record unit discharge of dopamine-containing neurons in the SNC and VTA during electrical stimulation of the LHb or adjacent structures. Dopamine-containing neurons in the SNC and VTA were identified by their characteristic spike duration (greater than 2 msec), discharge rate (2-8 spikes/sec), and irregular firing pattern. Analysis of peristimulus time histograms showed that 85% of SNC cells and 91% of VTA neurons were inhibited after single pulse stimulation (0.25 mA, 0.1 msec) of the LHb. The mean time between stimulation and onset of inhibition was 11 msec (range, 2-22 msec) and mean duration of maximal suppression was 76 msec (range, 20-250 msec). Stimulation of structures adjacent to the LHb (hippocampus, lateral thalamus, medial dorsal thalamus, medial habenula) had little or no effect. Destruction of the fasciculus retroflexus, the fiber pathway that contains most habenular efferents, blocked the stimulation effects on dopamine-containing neurons. Destruction of the stria medullaris, which contains most habenular afferents, did not alter the inhibitory effect of habenular stimulation. Injection of a cytotoxin, kainic acid, in the LHb 1 week before recording sessions blocked the inhibitory consequences of habenular stimulation. These experiments show that activation of neuronal perikarya in the LHb causes orthodromic inhibition of dopamine-containing neurons in SNC and VTA via the fasciculus retroflexus.     

Stimulus artifact compensation using biphasic stimulation

The feasibility of using biphasic stimulation as a method of reducing stimulus artifact was explored in several different circumstances. Sensory and muscle evoked potentials were compared using monophasic and biphasic constant-current stimuli. The monophasic stimulus was a negative rectangular pulse with a duration of 0.1-0.2 msec. The biphasic stimulus was a negative rectangular pulse of 0.1-0.2 msec duration followed, after a variable delay, by a positive rectangular pulse of the same duration and variable amplitude. When the conducting distances were long, stimulus artifact did not disturb either monophasically or biphasically evoked potentials. When the conducting distances were short, stimulus artifact occurred with monophasic stimulation but could be diminished readily using biphasic stimulation. The method can be accomplished easily using standard instruments with dual stimulators.     

Selectivity of attenuation (i.e., gating) of somatosensory potentials during voluntary movement in humans

Attenuation of somatosensory evoked potentials (SEPS) recorded from the scalp during voluntary movement occurs for specific combinations of the finger moved and the peripheral nerve stimulated. The cerebral potential component occurring at a latency of 27 msec (P27) evoked either by stimulation of median nerve at the wrist or by stimulation of 1st and 2nd digit nerves in the fingers were selectively attenuated during movement of 1st digit but were not altered during movement of 5th digit. By contrast, the cerebral P27 component evoked by stimulation of ulnar nerve at the wrist or by stimulation of 5th digital nerve were attenuated during movement of that digit but were not altered during movement of 1st digit. Gating of somatosensory activity is a selective phenomenon occurring when movement involves the areas being stimulated.