Neuromagnetic fields reveal cortical plasticity when learning an auditory discrimination task

Brain Research 764 Ž1997. 53–66

Research report

Neuromagnetic fields reveal cortical plasticity when learning an auditory discrimination task Selene Cansino a

a, )

, Samuel J. Williamson

b

Laboratory of CognitiÕe Psychophysiology, Psychology Faculty, National Autonomous UniÕersity of Mexico, Apartado Postal 25-308, Mexico City, DF 03421, Mexico b Neuromagnetism Laboratory, Departments of Physics and Psychology and Center for Neural Science, New York UniÕersity, New York, NY, USA Accepted 4 March 1997

Abstract Auditory evoked neuromagnetic fields of the primary and association auditory cortices were recorded while subjects learned to discriminate small differences in frequency and intensity between two consecutive tones. When discrimination was no better than chance, evoked field patterns across the scalp manifested no significant differences between correct and incorrect responses. However, when performance was correct on at least 75% of the trials, the spatial pattern of magnetic field differed significantly between correct and incorrect responses during the first 70 ms following the onset of the second tone. In this respect, the magnetic field pattern predicted when the subject would make an incorrect judgment more than 100 ms prior to indicting the judgment by a button press. One subject improved discrimination for much smaller differences between stimuli after 200 h of training. Evidence of cortical plasticity with improved discrimination is provided by an accompanying decrease of the relative magnetic field amplitude of the 100 ms response components in the primary and association auditory cortices. q 1997 Elsevier Science B.V. Keywords: Cortical plasticity; Learning; Magnetoencephalography ŽMEG.; Magnetic source imaging ŽMSI.; Auditory discrimination; Primary auditory cortex; Association auditory cortex

1. Introduction The relationship between physiological processes and cognitive performance has attracted considerable interest as the capabilities of techniques for functional brain imaging continue to be developed. The present study exploits the fine temporal resolution and spatial localization that is provided by the technique of magnetic source imaging ŽMSI.. The purpose of this investigation was to explore with macrophysiological recordings whether the functional organizations of auditory cortical areas exhibit plasticity with the improvement in performance as human subjects learn to discriminate small differences of intensity and frequency. Invasive physiological studies on animals have shown that learning can produce plasticity in the functional organization of sensory cortical areas. In visual studies, Zohary et al. w27x trained rhesus monkeys to discriminate fine ) Corresponding author. Fax: q52 Ž5 . 550-2560; E-mail: [email protected]

0006-8993r97r$17.00 q 1997 Elsevier Science B.V. All rights reserved. PII S 0 0 0 6 - 8 9 9 3 Ž 9 7 . 0 0 3 2 1 - 1

differences in the direction of a moving object and found that improvement in performance was related to neural sensitivity, as exhibited by a different time course and lowered threshold in single neuron activity. In somatosensory cortex, Jenkins et al. w11x found an enlargement of the cortical representation of a finger that was cutaneously stimulated in adult owl monkeys trained to contact a device that provided a cutaneous stimulus in order to obtain food rewards. In auditory cortex, studies with classical conditioning, where the animal learns to associate a tone with food or shock elicit stronger physiological response amplitudes to the conditioned stimulus and weaker responses for other stimuli, for both rat and guinea pig w2,7,8x. Sakurai w21,22x used a more complex task to study single unit activity in the rat auditory system: the rats were trained to make go or no-go responses to indicate whether the current tone was the same or different from the preceding tone. Cells in the auditory cortex exhibited delayed correlated activity following the tones, thereby indicating an involvement in retention. However, plasticity associated with behavioral learning

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S. Cansino, S.J. Williamsonr Brain Research 764 (1997) 53–66

has been less explored in humans. Ciesielski and French w4x used evoked potentials as a measure of the physiological effects of training for a visual matching task. Recordings obtained before and after a training period of about 2.5 h revealed an amplitude increase of about 15% for the N200 response component. In primary motor cortex, Karni et al. w13x, using functional magnetic resonance imaging ŽfMRI., found that the signal in primary motor cortex does not change in intensity after learning a sequence of finger movements, but there is an expansion of the extent of cortical representation for the trained sequence. Molchan et al. w17x, using positron emission tomography ŽPET., found an increased blood flow in primary auditory cortex during associative learning between an air puff to the right eye and a binaural tone to conditioning an eyeblink response. Human studies have generally explored plasticity related to short-term practice. However, the physiological plasticity associated with learning a task that requires many hours of training over the course of several months has not been reported before. Moreover, the classical learning task in animal studies is difficult to apply to human beings where no shock or food rewards are given, so such a task would not have the same significance. The present study was motivated by the experiments of Recanzone et al. w19x on the plasticity of the tonotopic locus in the primary auditory cortex of the owl monkey that correlates with the animal’s performance. These primates were trained for several weeks to discriminate small frequency differences in sequentially presented tone stimuli. Multiple-unit recordings showed an enlarged cortical representation and longer latency for the behaviorally relevant frequencies of trained monkeys than for the same frequencies presented to control monkeys. Physiological correlates during the process of learning can be explored by examining whether brain activity is related to the accuracy of the subject when performing a training task. If subjects do not exhibit an improvement in execution, we may expect that relevant physiological recordings should be the same in all trials, whether the response is correct or incorrect. However, once the subject’s performance improves, we may expect some difference between correct and incorrect responses that are reflected in physiological measurements, as behavioral data reflect shorter reaction times, accuracy, or subject’s confidence. This study exploits macrophysiological recordings to characterize neural population responses obtained with magnetic source imaging techniques to establish whether such measurements are sensitive to the subject’s performance during the process of learning an auditory discrimination task. The second goal is to characterize the plasticity of neural populations of primary and association auditory cortices in a human subject, to determine the number of learning trials that are required to produce a detectible change in physiological responses.

2. Materials and methods Studies were carried out on three right-handed subjects Žtwo females and one male. between the ages of 25 and 54 and with no history of hearing impairment. The authors participated as subjects. Tone stimuli were generated by an Amiga 1000 computer and presented via an Etymotic Research Type ER3-5A earphone to the side contralateral to where the neuromagnetic fields were recorded. This arrangement was chosen, because auditory neuromagnetic field patterns are stronger than for ipsilateral stimulation. The stimuli were 40 ms tone bursts with ramps of 2.5 ms for the onset and offset to reduce spectral spread. For the test stimuli, frequencies of 980, 1000 and 1020 Hz, and intensities of 82, 86 and 89 dB were presented in random order in each series of presentations. The following probe stimulus differed in frequency between 5 and 50 Hz and in loudness between 1 and 5 dB below and above the test stimuli presented in the specific trial. The difference in intensity and frequency between the test and the probe stimuli depended on the stage of the experiment Žsee below.. Each trial started with the presentation of the test stimulus followed by the presentation of the probe stimulus. The onset for the tone burst employed for the probe was delayed by 545 ms from the onset of the preceding stimulus. Immediately after the presentation of the sequence of the two stimuli, the subject pressed one of two buttons on a panel to indicate that test and probe stimuli were the same or the second button if the stimuli were different. After this response, the subject pressed one of three buttons on the same panel to indicate the confidence level for the judgment. The options were ‘‘sure’’, ‘‘insecure’’ and ‘‘not sure’’. After the subject responded, a green or red LED located 200 cm in front of the subject was displayed for 100 ms to give feedback on whether the response was correct or incorrect. The intertrial intervals were 1500, 2000 and 2500 ms presented in random order. Subjects responded to blocks of 300 trials, in which half of the test and the probe stimuli were the same and half were different. For trials where the test and probe stimuli differed, half were for frequency and half for intensity. Neuromagnetic field measurements were carried out within a magnetically shielded room with the subject comfortably reclined on a foam pad with head resting on a side while the subject performed the task described above. The magnetic field associated with the response was measured with a ‘‘Magnus’’ neuromagnetometer whose probe contains 37 sensors spanning a circular area of 144 mm diameter ŽBiomagnetic Technologies, San Diego, CA, USA.. The detection coil of each sensor has the geometry of a first order symmetric axial gradiometer with 5 cm baseline between adjacent coils. Separate recordings were made with the probe placed at three positions over each side of the head, where the field emerging from the head and returning to the head is strongest ŽFig. 1..

S. Cansino, S.J. Williamsonr Brain Research 764 (1997) 53–66

The existence of three distinct extrema indicates that the neural activity cannot be modeled by a single current dipole. Previous studies w3,15x have found that this pattern arises from two distinct sources, each of which may be modeled as a current dipole, one in the primary auditory cortex on the superior surface of the temporal lobe and the other in the auditory association cortex, located in the posterior region of the superior temporal sulcus. The responses observed at each of these locations consisted of three main components. One peak of interest in the waveform represents intracellular current directed toward the surface of the primary auditory cortex between 40 and 70 ms after stimulus onset and is commonly called the 50m component. A second peak of opposite polarity occurs between 70 and 140 ms and is denoted the 100m component of the primary auditory cortex. This peak was followed by a third component between 160 and 210 ms having the same polarity as the first peak and is denoted 180m. For the left hemisphere, one placement of the probe covered the anterior temporal region to record the field pattern of the inward field extremum associated with the 100m source of the primary cortex. A second placement of the probe over the ear recorded the inward field extremum associated with a source of 100 ms latency in the auditory association cortex, located in the posterior region of the superior temporal sulcus. This component is denoted as L100m. By happenstance, the outward field extrema for both 100m and L100m sources are superimposed in the parietal area, so only one placement of the probe was required to complete the field measurements. A similar procedure was carried out with field measurements over the right hemisphere to characterize the responses in that hemisphere. For each neuromagnetic recording position, the subject responded to blocks of 300 trials. In one session, recordings of one position on both sides of the head were carried out, so during each learning stage three recording sessions were performed for each subject on consecutive days. This procedure was employed in order to compare the same region of both hemispheres during the same stage of learning, since there was no knowledge of how fast the subject would be able to learn. The PPN headframe was used to express measurement positions relative to the scalp. This headframe is a cartesian coordinate system that is defined by the positions of three ‘‘cardinal landmarks’’ which can be accurately identified on the heads of individual subjects. These landmarks are the left and right periauricular points and the nasion, hence the shorthand ‘‘PPN’’ w26x. The origin of the PPN headframe lies midway between the left and right periauricular landmarks. The positive x-axis is defined as the line that extends from the origin to the nasion. The positive z-axis passes upward from the origin, directed perpendicular to the plan containing the x-axis and the line joining the two periauricular landmarks. The positive y-axis is perpendicular to both the x- and z-axes, extending from the origin to emerge from the left side of the head. The

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orthogonal coordinate position for the center channel of the probe was verified to be less than 5 mm different between sessions for the same recording regions. The positions of channel 1 during each session and for the three subjects are reported in Table 1. The rest of the channels present similar variation in positions. Recording epochs of 3000 ms began with a baseline of 1000 ms before the test stimulus was presented. The output of each sensor was bandpass filtered on-line from 0.1 to 100 Hz and was sampled at a rate of 297.6 Hz. Waveforms for ‘‘correct’’ and ‘‘incorrect’’ responses, and for ‘‘false alarm’’ Židentical tones judged to be different., ‘‘correct rejection’’ Židentical tones judged correctly., ‘‘hit’’ Ždifferent tones judged correctly. and ‘‘miss’’ Ždifferent tones judged to be the same. responses were separately averaged and filtered in a bandpass between 3 and 50 Hz. The amplitudes and corresponding standard deviations were determined by software routines for the latencies of interest. Different numbers of epochs went into each average waveform according to the kind of response. The standard error of the mean for each data point of the resulting waveforms was typically less than 15 fT. This may be compared with the amplitude of the 100 ms components, which are generally 100 fT or greater. At the beginning of a subject’s participation in the study, the individual’s discrimination levels for frequency and intensity differences were determined with the staircase method w14x. These measurements were obtained in order to establish the same level of task difficulty for each subject at the beginning of the learning phase. The discrimination levels in intensity and frequency that each subject was able to distinguish on 70% of the trials were 50 Hz and 5 dB for subject PB, 25 Hz and 4 dB for subject SW, and 30 Hz and 4 dB for subject SC. The neuromagnetic fields were recorded in four different stages. Subjects SW and SC participated in stages 1 and 2; PB participated in stages 1, 2, 3 and 4. Stage 1. The differences in frequency and intensity between the test and the probe stimuli were 5 Hz and 1 dB. These differences were used to elicit a chance level performance, 50% correct responses, in order to characterize the cortical response when subjects are unable to learn because the task difficulty is too high. Stage 2. The discrimination levels for frequency and intensity differences obtained with the staircase method for each subject were used. During this stage the subjects started to learn to distinguish between tones, and performance during this stage was correct about 75% of the trials. Stage 3. Neuromagnetic recordings were carried out for subject PB after about 135 h of learning to discriminate smaller differences between the two tone bursts following 47 800 trials. The subject’s discrimination improved from 50 to 15 Hz in frequency and from 5 dB to 1 dB in intensity. When the differences between the test and probe stimuli were 15 Hz and 1 dB, performance was correct for

S. Cansino, S.J. Williamsonr Brain Research 764 (1997) 53–66

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Fig. 1. Three regions of the scalp where the neuromagnetic probe was placed to record magnetic fields from auditory evoked responses in the left hemisphere: the anterior region for the inward field extremum of the primary auditory cortex; the lateral region over the ear for the inward field extremum of the auditory association cortex; and the parietal region for the outward field consisting of the overlapping extrema from both the primary and association cortices.

82% of the trials. A total of 135 h of training were carried out in the laboratory during a period of 68 days in daily sessions of 3 h except during the weekends. In each session the subject responded to 10 blocks of 200 trials, each block having the same proportion of stimuli as for the 300 trial blocks used in the neuromagnetic recordings. The difference in frequency and intensity between the test and probe stimuli was reduced as the subject’s performance improved. In a session, if the subject’s performance was about 80% correct in either frequency or intensity, reductions in the differences between the test and the probe stimuli were applied to that quality. These psychophysical experiments were also carried out in a shielded room as employed for neuromagnetic measurements. The subject sat in front of a computer that was the same kind as used in the neuromagnetic recordings and listened to the tones with the same kind of earphones. During these experiments the subject pressed designated keys to indicate the response and confidence level. There was no feedback after each trial; only at the end of each block the computer displayed to the subject the percent of correct responses. Subject PB was paid an hourly wage during her participation in the study; the other two subjects were not. PB was frequently encouraged by the experimenter to improve her performance. Stage 4. Neuromagnetic recordings were carried out in

Table 1 Positions Žcm. where the center channel of the probe was placed in the three recording regions during each stage for each subject Subject

Learning stage

Left x

Anterior region PB

SW SC

Ear region PB

SW SC

Parietal region PB

SW SC

Right y

z

x

y

z

1 2 3 4 1 2 1 2

4.5 4.1 4.6 4.6 5.0 4.6 5.7 5.2

10.2 10.1 10.6 10.1 11.3 11.2 9.3 9.8

7.3 7.1 6.8 7.3 3.9 4.1 3.7 3.3

4.4 4.8 4.9 4.7 5.0 4.5 5.1 5.2

y10.5 y10.2 y10.7 y10.6 y11.2 y11.1 y9.8 y10.0

6.8 6.9 6.7 6.4 4.8 5.3 5.2 5.4

1 2 3 4 1 2 1 2

y0.5 y0.3 y0.8 y0.6 0.5 0.0 y0.4 y0.1

12.0 11.9 11.5 11.6 11.6 11.7 10.5 11.0

y0.1 y0.2 y0.6 y0.6 y0.9 y1.3 1.9 1.4

y1.0 y0.5 y0.9 y0.5 0.4 0.2 y1.5 y1.8

y11.8 y11.6 y11.3 y11.3 y11.6 y11.8 y10.2 y10.7

0.1 y0.4 y0.3 y0.4 y0.4 y0.4 2.2 2.3

1 2 3 4 1 2 1 2

y2.0 y2.1 y2.2 y2.5 y2.7 y3.2 y4.7 y4.5

7.7 7.9 8.2 8.1 9.2 8.8 8.4 7.9

11.7 11.5 11.2 11.4 9.7 9.4 7.8 8.3

y0.3 y0.2 y0.1 y0.6 y2.8 y2.3 y4.7 y4.7

y8.7 y8.8 y9.2 y9.1 y9.2 y9.5 y8.2 y8.0

10.9 10.4 10.5 10.8 9.7 9.5 7.9 7.9

S. Cansino, S.J. Williamsonr Brain Research 764 (1997) 53–66

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assumption that the field is measured at the same locations but during different conditions, and that the error term has a chi-square distribution based on the sum of n independent random variables, each distributed normally, where n is the number of measurement sites. At any given time following the stimulus presentation, the contrast of each measurement site was defined as the ratio of the difference between the fields to the sum of the fields found in the two conditions. The statistic used was the mean of the site-bysite differences for the squared magnetic field amplitudes normalized by the mean of the square of the summed fields. The significance of this contrast was measured with t-tests. This was done for each subject in each stage, for field responses between the latencies of 1 and 750 ms for both left and right ear stimuli. In each contrast analysis, magnetic field values at a total of 100–105 measurement sites were obtained from the three recording positions of each side of the head, with noisy signals eliminated. This high number of sites decreases the variance of the contrast statistic. Only averages for each category of at least 40 epochs were used in the contrast statistical analysis. It should be noted that while a correction for spurious significances might be justified with this relatively large number of t-tests, a Bonferroni correction would be much too conservative. In this application, where patterns of significant contrast were sought, not too much importance was attached to isolated samples of significance, and emphasis was placed on intervals of significant values over appreciable time intervals.

Fig. 2. Number of trials required for subject PB to achieve finer discrimination levels between differences in frequency and intensity.

subject PB after 65 h more of training to discriminate even smaller differences, totaling 26 400 trials. The subject’s discrimination improved from 15 to 10 Hz. When the differences between the test and probe stimuli were 10 Hz and 1 dB, performance was correct on 68% of the trials. These 65 h of training were developed during 32 days in the same way as the previous 135 h of training described above. Fig. 2 shows the number of trials that subject PB executed in order to improve discrimination for the smaller frequency and intensity differences between test and probe tones. 2.1. Contrast analysis A key feature of the present study is to determine when two magnetic field patterns measured across the scalp are significantly different in strength or spatial distribution, indicating that sources differ. A useful measure is the ‘‘contrast’’ between the two field patterns w16x. The contrast of the evoked field between two conditions was computed for the following pairs of responses: correct vs. incorrect; hit vs. false alarm; hit vs. miss; hit vs. correct rejection; correct rejection vs. false alarm; correct rejection vs. miss; and false alarm vs. miss. This statistical analysis provides a measure for the relative difference in magnetic field patterns over the scalp produced by the evoked responses for any two conditions. It is based on the

3. Results 3.1. BehaÕioral data Table 2 summarizes the performance of the subjects during the four stages of learning. The dX values are consistent with the conditions of each stage; when performance was by chance dX values were close to 0 and when subjects began learning dX rose above 1.3. From stage 3 to 4, subject PB tried to improve discrimination from 15 to 10 Hz, and even though this subject subsequently worked

Table 2 Behavioral results for each subject during the four stages of learning Stage

1

2

3 4

Subject

PB SW SC PB SW SC PB PB

X

Correct responses Ž%.

d

52 48 50 83 74 74 82 68

0.1 0.0 0.1 1.9 1.4 1.3 1.8 1.0

b

1.0 1.0 1.0 1.2 0.8 1.0 1.1 1.1

Reaction time Žs. Incorrect

Frequency correct responses Ž%.

Intensity correct responses Ž%.

Confidence level Ž%.

Correct

Not sure

Insecure

Sure

1.79 1.53 1.46 1.23 1.31 1.35 0.82 0.68

1.90 2.12 1.39 1.75 1.98 1.72 1.01 0.89

48 54 71 71 65 86 82 62

53 57 74 89 76 61 78 69

28 8 75 14 4 21 1 1

44 49 19 18 12 46 17 34

28 43 6 68 84 33 82 65

S. Cansino, S.J. Williamsonr Brain Research 764 (1997) 53–66

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with stimuli differences of 10 Hz and 1 dB for 26 400 trials, the performance during stage 4 did not improve above 68% correct responses. None of the subjects were biased in the way they responded to the task, as denoted by their b criterion likelihood ratio. A b value of about 1.0 is a neutral or moderate criterion, which indicates a lack of response bias toward either the same or different judgment. With practice, reaction time tends to decrease, as clearly seen in subject PB who practiced the task for several months. Reaction time is also sensitive to the subject’s performance, with a longer reaction time exhibited for wrong responses than for correct responses. Subjects PB and SW were better in discriminating intensity differences than frequency differences, while the opposite was exhibited for subject SC. The confidence levels are consistent with the subject’s performance in each stage: a higher confidence level is exhibited for all subjects during stage 2 compared with their judgments in stage 1. In addition, the reaction times of the three subjects are associated with

their confidence levels: as subjects become more confident with the task, reaction times decrease. 3.2. Neuromagnetic data The contrast statistical analysis reveals no difference between the responses to the pair of tones during the first stage, when a subject’s performance was at chance. During stage 2, when subjects started to improve their discrimination and their performance was about 75%, the results of the contrast analysis were not significant during the portion of the first 550 ms while the test stimulus is presented. It is during approximately 70 ms after the onset of the probe stimuli that the field contrast analysis is significant between the following pair of responses: correct vs. incorrect, hit vs. false alarm, hit vs. miss, correct rejection vs. false alarm, and correct rejection vs. miss. No difference was found between hit vs. correct rejection responses and between miss vs. false alarm responses. These results are

Table 3 Field contrast percentage for subject PB during stage 2 of learning at different latencies ŽLat. after onset of the probe stimulus for the following pair of responses: correct vs. incorrect ŽC-I., false alarm vs. hit ŽF-H., hit vs. miss ŽH-M., correct rejection vs. false alarm ŽCR-F. and correct rejection vs. miss ŽCR-M. Lat.

Left

Right

C-I 551 554 558 561 565 568 571 575 578 581 585 588 591 595 598 601 605 608 612 615 645 649 652 655 659 662 665 669 672 675 679

y15.4 y7.0 1.9 3.9 y4.1 y14.6 y19.9 y19.7 y21.3 y18.8 y15.0 y11.4 y8.7 y5.9 y1.2 2.6 y10.3 y12.6 y8.6 y7.4 y4.8 y5.8 y6.8 y2.7 4.0 1.9 y1.6 y1.5 y1.7 y2.8 y3.8

F-H

H-M b

a

a

24.5 32.0 c 29.4 c 27.4 c 26.1 b 23.8 a 27.1 c 31.1 c 31.8 c 27.5 c 21.2 a 15.4 12.4 10.4 6.8 5.0 10.1 5.9 6.0 8.4 11.5 9.9 8.5 11.5 10.2 5.6 y3.1 y4.0 y0.2 1.5 4.2

y11.8 y7.0 y3.6 y4.9 y11.4 y18.3 y22.4 a y21.4 a y19.3 y17.9 y15.6 y12.7 y9.4 y5.8 y0.5 9.4 14.9 y0.4 y5.8 y7.7 y16.9 y20.1 a y24.8 b y28.6 c y16.4 y5.8 y0.7 2.2 1.9 y1.8 y6.3

CR-F y17.0 y17.7 y21.2 a y26.9 c y26.1 b y25.0 b y24.7 b y25.2 b y27.6 c y24.0 b y20.5 a y16.3 y14.5 y12.6 y7.3 y4.5 y18.8 y23.4 a y10.9 y7.5 y3.3 y3.8 y1.4 5.6 3.8 y10.2 y7.7 y8.1 y10.9 y9.4 y6.2

CR-M y19.2 y10.5 y7.2 y9.3 y12.3 y16.7 y18.5 y17.8 y21.2 y21.7 y18.9 y14.1 y10.5 y8.0 y2.3 6.4 3.7 y14.5 y10.2 y6.6 y7.4 y8.4 y8.4 y4.4 y4.2 y11.2 y12.9 y11.3 y10.1 y10.5 y9.5

C-I

F-H c

a a

y27.3 y34.6 d y37.9 d y34.8 d y10.7 y5.2 y12.0 y14.8 y20.1 a y24.2 b y21.6 a y17.0 y15.1 y14.8 y13.7 y14.9 y10.3 y6.9 y4.0 y1.2 y19.2 a y23.8 b y24.3 c y21.0 a y15.4 y9.4 y5.6 y4.5 y4.7 y5.8 y6.0

H-M c

31.3 37.5 d 40.9 d 46.0 d 50.3 d 42.0 d 33.0 c 25.1 b 22.8 a 31.7 c 33.5 c 30.9 c 28.5 c 27.0 c 25.1 c 19.1 7.8 1.9 y1.1 y2.9 21.1 a 23.8 b 25.6 c 25.6 c 22.9 a 16.4 8.6 y4.5 y5.1 3.0 10.9

Negative contrast values indicate greater field power for the second type of responses in the pair. a P - 0.05; b P - 0.02; c P - 0.01; d P - 0.001.

CR-F d

y37.7 y35.8 d y33.9 c y30.7 c y21.7 a y20.6 a y26.7 c y34.0 d y37.4 d y33.7 d y31.0 c y32.1 c y34.4 d y36.2 d y37.2 d y31.0 c y21.7 a y14.8 y10.4 y6.8 y16.7 y15.6 y15.4 y16.9 y17.0 y14.9 y12.4 y11.1 y11.0 y10.7 y8.0

CR-M d

y36.2 y35.6 d y35.7 d y38.7 d y42.2 d y38.7 d y30.7 c y20.6 a y12.8 y23.5 a y27.5 c y25.8 c y26.1 c y28.0 c y32.1 c y32.7 c y10.2 y1.3 1.9 3.5 y25.4 c y32.1 c y30.6 c y21.5 a y15.9 y12.8 y10.1 y7.9 y5.1 y8.5 y11.7

y32.0 c y38.3 d y39.8 d y25.8 b y18.4 y21.3 a y28.2 c y32.2 c y30.4 c y27.2 c y25.9 c y26.8 c y30.1 c y33.8 d y35.5 d y28.2 c y20.2 a y14.2 y10.0 y6.4 y20.6 a y24.2 b y24.5 b y24.6 b y23.7 b y21.3 a y20.3 a y20.8 b y19.2 a y15.3 y9.5

S. Cansino, S.J. Williamsonr Brain Research 764 (1997) 53–66

presented in Table 3, Tables 4 and 5 for subjects PB, SW and SC respectively, where the contrast percentages at different latencies after the onset of the probe stimulus during stage 2 are exhibited for right and left hemisphere recordings. The contrast analysis shows that incorrect, false alarm and miss responses have a larger field power than correct, hit and correct rejection responses for subject PB for over both left and right hemispheres. The same significant results are observed for subject SW except between hit and miss responses on the right hemisphere. PB also presents a stronger field pattern for the probe stimulus with incorrect, false alarm and miss responses compared with correct, hit and correct rejection responses for latencies that correspond to the 100 ms components over the right hemisphere. At these latencies, SW also exhibited a stronger field pattern but for miss responses compared with hit responses on both hemispheres and for false alarm responses compared with hit responses on the right hemisphere. The contrast field patterns for subject SC were less significant, but the contrast analysis for this subject displayed the same tendency as for the other

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subjects. SC presents a stronger field pattern for false alarm responses compared with correct rejection responses over both hemispheres and for false alarm responses compare with hit responses on the left hemisphere. The results obtained during stages 3 and 4 of learning for subject PB are displayed in Tables 6 and 7 respectively. During stage 3, after the subject has improved discrimination from 5 to 1 dB and from 50 to 15 Hz, the field contrast is still significantly different between all pairs of correct and erroneous responses having the same pattern as in stage 2. The contrast percentage is greater over the right hemisphere and during the first 50 ms following the onset of the probe. During stage 4, after subject PB slightly improved discrimination from 15 to 10 Hz on progressing from stage 3 to 4, the field contrast between all pairs of correct and erroneous responses is also significant over both hemispheres except for correct and incorrect responses. The field strength is always larger for erroneous responses than for correct responses. Fig. 3 shows the t-values of the field contrast between hit and miss responses for

Table 4 As for Table 3 but for subject SW Lat.

Left C-I

F-H

H-M

CR-F

CR-M

C-I

F-H

H-M

CR-F

551 554 558 561 565 568 571 575 578 581 585 588 591 595 598 601 605 608 612 615 645 649 652 655 659 662 665 669 672 675 679

y27.6 c y25.8 b y23.6 b y24.4 b y26.2 c y28.1 c y31.9 c y33.8 c y29.2 c y23.0 b y19.6 a y18.1 y17.3 y17.4 y17.7 y17.9 y15.1 y9.8 y8.8 y10.8 y8.4 y8.4 y9.2 y10.8 y12.8 y14.6 y14.8 y12.7 y10.1 y6.8 y2.9

46.7 d 46.3 d 45.9 d 39.3 d 30.9 c 26.8 c 30.1 c 38.2 d 35.1 d 29.7 c 26.3 c 25.4 c 24.8 b 22.8 a 19.4 22.2 a 30.7 c 20.0 a 13.0 9.5 5.9 6.8 8.5 10.6 11.9 13.9 16.7 18.7 18.7 15.1 7.0

y26.3 c y25.7 b y24.3 b y22.8 a y22.6 a y24.3 b y29.1 c y34.7 d y36.7 d y32.7 d y27.9 c y25.6 c y24.6 b y23.0 b y20.6 a y20.3 a y23.0 a y13.7 y5.6 y6.9 y11.7 y12.6 y14.7 y17.6 y20.2 a y23.0 b y26.7 c y31.0 c y33.5 c y24.7 b y12.7

y32.2 c y40.4 d y44.9 d y38.1 d y27.4 c y18.6 y11.0 y8.6 y11.2 y14.7 y18.7 a y22.5 b y25.4 c y27.3 c y27.5 c y23.2 a y17.9 y18.1 y18.5 y18.1 y5.9 y5.4 y4.7 y4.9 y6.4 y9.2 y12.1 y13.8 y13.8 y12.8 y11.2

y22.1 a y21.9 a y18.9 y18.1 y22.2 a y31.1 c y40.2 d y42.8 d y37.8 d y34.2 d y35.5 d y38.0 d y37.5 d y35.5 d y32.3 c y26.7 c y17.8 y10.2 y11.0 y18.1 y12.7 y12.4 y12.4 y13.1 y14.5 y15.7 y15.2 y14.4 y18.4 y24.4 b y23.6 a

y5.3 y5.8 y6.3 y8.1 y13.5 y19.7 a y22.6 a y21.1 a y21.9 a y21.4 a y19.1 y17.0 y15.2 y14.2 y12.2 y6.4 y3.9 y5.6 y5.6 y2.8 y2.9 y4.0 y5.4 y7.8 y10.7 y12.5 y12.1 y10.3 y6.0 y1.4 y1.7

y4.5 y4.9 y6.9 y5.0 8.1 18.5 22.8 a 24.4 b 25.1 b 25.7 b 25.6 c 25.8 c 27.1 c 30.0 c 31.0 c 26.3 c 20.0 a 16.6 15.3 12.1 1.4 3.9 6.4 19.7 a 20.8 a 20.6 a 23.1 a 23.0 b 23.3 b 24.3 b 22.7 b

7.2 3.9 1.8 0.6 y1.9 y9.0 y13.8 y8.3 y7.0 y12.2 y15.9 y13.8 y9.1 y7.3 y7.3 y6.3 y7.7 y12.5 y15.8 y12.9 y8.9 y9.6 y10.5 y12.6 y15.9 y19.0 y20.4 y21.6 y24.8 y23.4 y18.0

y23.3 y19.5 y17.0 y18.0 y21.8 y26.3 y33.0 y39.4 y36.2 y29.2 y24.4 y21.3 y19.2 y18.4 y18.3 y17.9 y16.1 y13.8 y12.2 y9.5 y1.8 y3.1 y5.4 y11.1 y10.3 y8.4 y9.4 y16.1 y21.8 y23.5 y18.8

a

P - 0.05;

b

P - 0.02;

Right

c

P - 0.01;

d

P - 0.001.

a a a b b

CR-M a

a b c d d c b a a a a

a b a

y22.7 y25.3 y24.5 y21.9 y18.1 y17.7 y19.6 y20.7 y28.2 y28.0 y22.3 y19.7 y18.0 y18.0 y18.5 y17.6 y15.2 y14.8 y14.3 y9.4 y9.5 y9.8 y11.1 y12.7 y13.6 y13.2 y12.9 y14.4 y15.8 y15.4 y15.2

a b b a

a c c a

S. Cansino, S.J. Williamsonr Brain Research 764 (1997) 53–66

60

Fig. 3. On the left, t-values from the field contrast statistic between 550 ms and 750 ms Žat 4 ms intervals. during stage 1 and 2, for hit and miss responses, for the left hemisphere of subject PB. Negative contrast values show greater field power for miss responses. On the right side, waveforms recorded in one of the channels located in the anterior region of the left hemisphere. Differences between hit and miss responses are only present during stage 2 of learning.

subject PB during stages 1 and 2 over the left side of the head. The negative t-values indicate that miss responses have stronger field patterns than hit responses. The contrast is significant between these two kinds of responses during the first 30 ms and about 100 ms after the onset of the probe stimulus in stage 2 but not in stage 1. This figure

shows at the right side one of the waveforms that were used to compute the contrast. This waveform, recorded with the left anterior placement, indicates that the 50m and 100m components contributed to the significant field contrast found between hit and miss responses. Magnetic field measurements of parietal and ear regions also contributed

Table 5 As for Table 3 but for subject SC Lat.

551 554 558 561 565 568 571 575 578 581 585 588 591 595 598 601 605 608 612 615 645 649 652 655 659 662 665 669 672 675 679 a

Left

Right

C-I

F-H

H-M

CR-F

y10.1 y7.1 y0.8 4.9 6.0 y0.6 y7.2 y11.4 y15.2 y16.5 y15.0 y12.3 y9.3 y6.9 y4.6 y2.4 y0.2 y0.3 y13.1 y13.5 y4.4 y4.2 y3.7 y2.6 y0.6 2.3 5.6 6.8 0.9 y6.4 y6.5

15.1 8.9 y3.6 y12.3 y10.4 y2.0 5.6 9.6 12.3 7.7 12.7 9.3 5.0 2.5 2.2 3.8 7.6 16.8 28.3 21.4 5.0 5.1 4.5 3.6 2.4 1.1 2.0 9.9 20.5 19.1 11.4

y5.8 y1.0 4.3 8.6 10.4 5.8 y3.3 y10.6 y15.0 y15.0 y12.2 y9.7 y7.8 y6.9 y6.7 y6.5 y5.3 y2.8 y6.9 y6.0 y4.9 y4.5 y3.5 y2.0 0.1 2.8 5.8 6.6 y3.2 y11.1 y12.9

y24.2 y23.2 y18.1 y8.6 y6.2 y11.5 y12.5 y13.6 y16.1 y17.3 y16.9 y14.6 y10.6 y4.9 0.1 1.8 y0.6 y11.9 y26.6 y25.2 y3.6 y3.5 y3.5 y2.9 y0.9 1.9 3.3 y1.6 y11.7 y17.2 y13.0

P - 0.05;

b

P - 0.02;

c

c a

a

P - 0.01;

d

P - 0.001.

b a

c c

CR-M

C-I

F-H

H-M

CR-F

y12.6 y12.9 y13.8 y11.0 y5.8 y6.9 y10.6 y14.9 y19.4 a y20.8 a y19.1 a y15.9 y13.2 y9.7 y5.1 y1.2 1.4 1.4 y6.6 y11.8 y3.6 y3.1 y2.6 y1.4 1.3 5.4 9.9 13.4 11.5 y4.6 y17.9

y15.1 y13.9 y3.6 y1.6 y12.9 y10.0 y0.1 4.3 5.1 4.2 2.8 1.3 0.0 y1.4 y3.4 y6.9 y11.0 y4.8 3.1 3.3 y1.6 y1.8 y1.9 y2.4 y3.3 y4.1 y4.7 y5.6 y9.1 y12.9 y3.8

3.0 2.1 4.0 1.5 19.6 19.6 19.1 15.5 10.7 4.2 y2.2 y2.9 y1.0 2.0 5.9 10.0 14.6 11.2 2.3 y2.9 1.5 1.6 1.4 2.5 5.3 8.2 7.8 5.2 6.3 8.6 3.0

y6.6 y6.3 y2.7 y0.8 y6.7 y12.7 y9.4 y6.5 y8.2 y9.3 y9.6 y9.6 y9.4 y9.4 y9.4 y8.6 y3.3 4.8 4.5 2.5 y2.8 y3.0 y4.0 y5.6 y7.7 y9.6 y9.8 y10.2 y13.5 y23.6 y21.9

y19.4 y25.6 y27.8 y27.4 y16.3 y6.9 y0.0 2.9 4.9 6.8 9.4 8.0 4.6 1.0 y2.5 y7.0 y12.5 y14.2 y4.9 1.1 2.3 2.3 2.3 1.6 1.0 1.0 1.1 1.0 y1.4 y9.1 y7.9

a a

CR-M a b b

y24.3 b y23.1 a y14.5 y6.4 2.9 3.9 12.2 10.3 3.9 y1.4 y4.4 y4.7 y5.1 y5.4 y4.2 y2.8 y0.2 y0.6 2.0 0.9 1.0 0.9 y0.4 y1.4 y1.4 y0.8 y1.8 y5.4 y10.2 y21.6 a y28.0 b

S. Cansino, S.J. Williamsonr Brain Research 764 (1997) 53–66

61

Fig. 4. As for Fig. 3, except showing subject SW waveforms recorded in one of the channels located in the parietal region of the left hemisphere. As in Fig. 3, differences between hit and miss responses are only present during stage 2 of learning.

to the significant contrast pattern found during the second stage of these experiments. It is important to notice that no amplitude difference is evident for evoked magnetic components between the hit and miss responses associated with the test stimuli, only for the probe stimuli. This is a reliable control to verify that the difference between the field contrasts, for hit and miss responses, is associated

with the probe stimulus, not to the fewer epochs used for the waveform average of this class of responses. Moreover, the average amplitude of the waveforms in each category of response recorded during stages 1 and 2 is the same, even though different numbers of epochs were used to calculate the average waveforms. This characteristic was seen at all recording sites.

Table 6 As for Table 3 but for subject PB during stage 3 of learning Lat.

551 554 558 561 565 568 571 575 578 581 585 588 591 595 598 601 605 608 612 615 645 649 652 655 659 662 665 669 672 675 679 a

Left

Right

C-I

F-H

H-M

CR-F

CR-M

C-I

F-H

H-M

CR-F

CR-M

3.1 8.7 y0.7 y4.3 y5.5 y7.1 y11.2 y14.9 y19.0 y15.2 y8.6 y5.5 y6.1 y10.2 y24.4 y29.8 y20.2 y11.8 y5.3 y0.4 9.2 9.9 y11.5 y9.8 y6.7 y4.1 y2.8 y1.5 0.8 2.8 2.1

29.5 c y10.3 y7.2 y2.8 5.7 17.5 25.3 b 28.7 c 32.5 c 26.1 b 16.7 15.2 18.3 31.9 c 33.4 c 16.7 6.5 2.3 y1.7 y5.7 19.7 14.1 10.0 10.3 6.2 0.8 y0.4 1.7 4.6 5.7 5.9

y2.2 y2.9 y6.6 y6.7 y3.6 y5.4 y22.0 a y25.6 b y23.7 a y8.5 y2.9 y2.7 y19.4 y33.7 c y43.5 d y45.5 d y34.9 d y23.1 b y13.1 y4.3 y30.1 c y23.7 a y8.7 y4.9 y2.5 y1.6 y0.6 1.6 4.1 2.8 y2.8

y6.8 18.8 y0.3 y5.8 y11.5 y17.0 y17.5 y17.1 y19.7 y21.5 y18.1 y12.2 y8.9 y15.9 y30.5 y35.6 y25.8 y14.2 y6.4 y1.7 y4.8 y1.7 y20.8 y18.1 y12.2 y6.7 y5.7 y6.3 y4.8 y1.6 1.0

9.1 y4.4 y12.8 y14.5 y9.3 y4.2 y6.6 y7.5 y8.5 y9.8 y7.4 0.4 0.7 0.7 y16.1 y50.6 y38.7 y29.7 y21.5 y11.7 y0.4 3.0 y19.0 y14.3 y9.0 y8.0 y7.0 y3.1 3.5 6.2 2.7

y3.3 y27.3 c y37.5 d y34.1 c y18.5 y13.1 y19.4 y22.6 a y29.5 c y27.7 c y30.5 c y36.0 d y22.2 b y15.9 0.3 4.4 2.2 0.3 y0.9 y1.7 y11.3 y14.0 7.2 7.5 5.9 2.0 y2.3 y4.7 y4.5 y3.9 y4.5

26.7 b 37.0 d 33.7 c 35.2 d 37.0 d 39.7 d 38.4 d 24.2 b 19.0 21.5 a 17.7 20.3 a 15.9 15.2 10.8 5.6 2.5 0.5 1.8 3.7 28.0 c 30.3 c y12.0 y10.5 y2.3 9.3 11.7 9.2 9.0 9.1 10.1

y8.0 y26.3 b y30.0 c y31.2 c y22.0 a y15.1 y25.2 b y39.9 d y35.1 d y27.2 c y26.0 c y34.7 b y40.8 d y27.7 c y6.3 y0.3 y0.7 y1.7 y2.5 y2.9 y14.0 y15.7 6.1 5.6 2.4 y2.2 y6.9 y8.4 y6.5 y3.6 y2.9

y18.5 y29.9 c y34.1 c y29.9 c y29.7 c y41.8 d y32.6 c y17.1 y10.3 y18.1 y20.0 y9.3 y14.2 y21.9 a y17.4 y13.8 y8.5 y4.0 y3.0 y3.5 y23.2 a y28.0 c y0.3 1.7 y4.8 y13.2 y11.8 y7.1 y6.3 y8.4 y10.6

4.9 y15.4 y22.9 a y11.9 y3.7 y9.6 y18.2 y23.1 a y27.8 c y29.5 c y35.5 d y40.3 d y36.0 d y27.0 c y10.7 y7.8 y6.6 y5.1 y3.6 y2.6 y18.6 y19.1 y4.2 y2.1 y2.5 y4.7 y5.9 y5.8 y4.0 y3.1 y3.3

P - 0.05;

b

b c a

P - 0.02;

c

P - 0.01;

d

P - 0.001.

a a

c d b

a

d d c b

a

S. Cansino, S.J. Williamsonr Brain Research 764 (1997) 53–66

62

Table 7 As for Table 3 but for subject PB during stage 4 of learning Lat.

Left C-I

551 554 558 561 565 568 571 575 578 581 585 588 591 595 598 601 605 608 612 615 645 649 652 655 659 662 665 669 672 675 679 a

y7.6 y13.0 y15.0 y11.0 y7.2 y8.9 y11.0 y13.0 y15.0 y4.1 6.1 12.6 6.8 1.0 y1.7 1.9 4.4 2.1 0.2 y0.5 y0.9 2.1 3.0 1.6 1.1 1.6 1.8 1.8 1.4 1.3 0.8

P - 0.05;

b

Right F-H

P - 0.02;

H-M c

CR-F a

27.5 30.2 c 28.5 c 22.6 a 23.3 a 22.2 a 5.1 4.3 13.5 15.9 12.6 12.9 18.9 30.9 c 32.6 c 24.4 b 14.4 7.0 5.7 6.1 20.8 a 18.8 7.8 y4.5 y4.6 y0.8 3.1 3.6 1.8 1.6 2.6

y20.5 y26.2 c y28.7 c y30.7 c y31.5 c y31.5 c y31.0 c y27.5 c y22.9 a y15.3 y15.6 y21.1 a y19.2 y21.8 a y22.3 a y16.2 y9.1 y3.0 y1.5 y2.4 y15.3 y12.7 y9.1 y5.8 y3.1 y3.3 y6.0 y7.7 y6.3 y3.7 y1.5

c

d

P - 0.01;

CR-M d

y35.1 y35.7 d y28.5 c y17.9 y15.5 y24.5 b y28.6 c y25.0 b y28.2 c y20.9 a y13.1 y11.1 y14.4 y20.0 a y21.1 a y19.5 y14.6 y6.6 y3.2 y2.7 y9.2 y4.5 4.3 11.6 11.2 7.6 3.1 0.5 y0.4 y2.0 y3.4

y8.1 y16.4 y23.0 y24.2 y22.7 y26.0 y35.2 y43.2 y34.6 y16.6 y10.0 y17.5 y18.5 y17.0 y16.6 y16.1 y10.7 y2.5 1.3 1.3 y8.3 y4.6 y2.9 y0.1 3.3 3.2 0.1 y2.9 y4.0 y3.6 y2.1

C-I

a b a b d d c

y11.3 y21.3 y24.7 y7.1 0.6 y1.3 y9.4 y20.8 y18.6 y10.9 y5.2 y5.5 y17.9 y16.1 y2.6 y0.3 y0.6 y1.4 y2.4 y3.1 6.0 8.9 6.5 2.7 y0.9 y3.6 y3.5 y1.4 0.3 0.9 2.4

F-H

H-M b

a b

a

25.1 24.8 b 20.7 a 14.5 6.0 12.4 28.4 c 38.6 d 32.2 c 25.1 b 25.3 b 28.7 c 34.7 c 35.2 d 23.5 a 10.4 2.7 y0.1 y0.1 0.6 9.4 14.6 19.7 22.5 a 22.9 a 20.3 a 13.1 9.8 12.8 13.0 10.8

y10.6 y31.6 c y38.1 d y35.0 c y20.7 a y13.5 y27.9 c y37.3 d y37.2 d y34.9 c y33.6 c y30.9 c y27.0 b y30.5 c y19.4 y3.0 0.3 0.2 y0.6 y1.8 y22.0 a y20.6 a y1.4 y6.0 y5.0 y7.7 y12.0 y14.1 y14.1 y12.0 y9.5

CR-F y20.6 y19.6 y15.1 2.0 9.5 1.3 y11.7 y19.3 y18.5 y18.1 y23.2 y30.6 y29.4 y25.6 y19.5 y11.6 y5.4 y1.8 y0.5 y0.3 y7.4 y15.8 y21.5 y23.4 y23.0 y18.8 y9.0 y4.5 y7.2 y8.8 y8.7

CR-M a

a c c b

a a a

7.7 y14.7 y29.1 c y21.4 a y5.9 1.6 y12.7 y23.9 a y25.9 b y25.7 b y28.0 c y34.0 c y37.0 d y33.1 c y13.7 y4.8 y2.8 y1.8 y1.2 y1.5 y11.2 y2.6 y4.8 y6.6 y3.7 y5.1 y8.7 y10.2 y10.0 y8.6 y57.4

P - 0.001.

Fig. 4 displays the t-values from the contrast percentage for hit and miss responses, obtained over the left hemisphere of subject SW. This subject has a significantly strong contrast between hit and miss responses, with a

stronger field for miss responses during the first 70 ms after the onset of the probe and near the latencies corresponding to the 100 ms components. At the right side of the figure are waveforms recorded by one of the sensors

Fig. 5. As in Fig. 3, but for correct rejection and false alarm for the left hemisphere of subject SC. Negative contrast values indicate greater field power for false alarm responses. On the right, waveforms recorded in one of the channels located in the parietal region of the left hemisphere. Differences between correct rejection and false alarm responses are only present during stage 2 of learning.

S. Cansino, S.J. Williamsonr Brain Research 764 (1997) 53–66

located over the left parietal placement of this same subject. The amplitude for miss responses during stage 2 for the 50 ms and 100 ms components elicited by probe stimuli reflects this strong field contrast. This waveform is clearly stronger than the waveforms for hit responses of stage 2 and for hit and miss responses recorded during stage 1. The results of contrast analysis between correct rejection and false alarm responses for subject SC are plotted in Fig. 5, where the t-values during stages 1 and 2 for the left side of the head are exhibited. The contrast is significant near the latencies of the 100 ms components elicited by the probe stimulus. The waveforms at the right side of this figure are recordings for the left parietal placement, showing how the 100 ms components for the false alarm condition in stage 2 contributed to this significant contrast. To explore the physiological correlates of neural responses in the primary and association cortices with the process of learning over several months to discriminate small differences between tone burst stimuli, averages were obtained separately from the anterior and ear sites to record the 100m and L100m components respectively, using measurements from the seven channels where the evoked magnetic response was strongest. Separate averages were obtained for components elicited for the test and the probe stimuli, for both left and right hemispheres. These results, obtained for subject PB, are displayed in Fig. 6. The 100 ms responses for both primary and association auditory cortex tend to decrease with duration of training. This trend is the same for the neural responses elicited by both the test and the probe stimuli, and they are stronger over the right hemisphere than the left. Fig. 7 presents the average waveforms for all classes of responses for each stage of performance recorded by one of the channels placed over the parietal region of the right hemisphere of subject PB. In this area the extrema of both the 100m and L100m components are superimposed.

63

Fig. 7. Average waveforms of all types of responses during each stage of learning recorded in one of the channels located in the parietal region of the right hemisphere of subject PB, where responses of the primary and association cortices are superimposed.

Therefore, any plasticity in the responses in primary and association auditory cortex is added. These two waveforms show a clear amplitude decrease during the time the subject learns to discriminate, with a corresponding improvement in performance.

4. Discussion The contrast analysis employed in this study provides evidence for significant differences exhibited in cortical activity while a subject is resolving whether two tones are the same or different. This activity is indicated by stronger neuromagnetic evoked responses when the subject is wrong than when correct. The few previous studies that addressed the possibility that brain activity reflects differences be-

Fig. 6. Average amplitudes of the 100m component of the primary auditory cortex and of the L100m component of the auditory association cortex elicited by the test and probe stimuli over left and right hemisphere of subject PB, during the four stages of learning. A typical standard deviation for field values is 15 fT.

64

S. Cansino, S.J. Williamsonr Brain Research 764 (1997) 53–66

tween correct and incorrect responses have found more consistent results regarding differences in the latency of the evoked potential than in the amplitude. For instance, the P300 component exhibited longer latencies in erroneous trials than in correct trials w5,6,18x. Regarding amplitude differences, Renault et al. w20x found that the N200 and P300 evoked potentials were larger in erroneous trials, while Falkenstein et al. w9x found a decrease of the P300 component and an increase of a slow wave between 500 and 700 ms for incorrect trials. The contradiction between these previous studies might be due to the fact that differences were based on the amplitude of the evoked potentials, which are known to be more affected by variables such as attention, motivation, etc. than latency measurements. The results from the present study were obtained by using a contrast analysis which has proved to be a sensitive measure of the difference in the neuromagnetic field pattern between two conditions recorded from the same regions, where the amplitudes and variance of more than 100 recording sites are considered for the calculations. So the difference between correct and erroneous responses is related to a field pattern within a time interval and not with amplitude measurements at one value of latency. Falkenstein et al. w9x found also a fronto-central evoked potential component that was identified as the error negativity Ž NE . component that appears only for incorrect responses and is time-locked closer to the motor response of the subject than to the stimulus. Therefore, this component might be associated with a reflective reaction of the subject when realizing that an error has occurred. The fact that we found early and not late differences between correct and incorrect cortical responses at the onset of the probe reflects another kind of error processing. Following the proposal of Donchin et al. w6x, the difference between correct and incorrect responses might be related to a subject’s recognition of an error that does not necessarily reach the subject’s awareness. We suggest that the stronger contrast field pattern found in error trials compared with correct trials might reflect that an early processing of the probe stimulus is executed in an uncertain or partial way, and additional resources are called into play. An increase in arousal may also explain these findings, because the signal indicating that the subject is about to make an incorrect response is observed during the first 70 ms following the onset of the second tone and sometimes also near the 100 ms components. Moreover, these significant field contrasts were obtained only when the subject was able to learn from the task and not when the subject’s performance was by chance. Learning occurred when the subject had some confidence in the accuracy of judgments. Subject SC exhibited less significant contrast differences between correct and erroneous responses. However, this subject also exhibited a lower confidence and lower dX than subjects PB and SW, which might reflect that SC was less sensitive to stimulus discrimination than the other two subjects.

The contrast between field patterns was significant for latencies that correspond to the 50 ms and 100 ms response components, which indicates that correct-incorrect processing is related with specific cortical components. These early latencies are time-locked to the presentation to the probe stimulus, so the present study indicates that comparison is made at an early stage, beginning at least with the 50 ms component. This finding differs from previous human studies that showed differences for later components, viz. N200 and P300 w9,20x. However, the present results are similar to the effects found in animal studies where single unit recordings of responses sensitive to learning are exhibited between 25 and 50 ms w8x. The present experiments demonstrated that the discrimination level can be improved if the subject dedicates enough time to achieve this goal. Subject PB had to execute about 74 000 trials to improve discrimination from 50 to 10 Hz and from 5 to 1 dB. The learning performance shows that the subject required more trials as the differences between the tones became smaller. Neural plasticity has been described for previous experiments as an increase in the neuronal response strength and as an expansion of the representation across the cortical area associated with the stimulus Žfor a review see Kaas w12x and Weinberger w25x.. Increases in amplitude of neural responses have been detected using single unit recording techniques in classical conditioning experiments with animals w1,2,8x; an enlargement of cortical area representations have been found in monkeys using single unit recording methods w11,19x and in human subjects using evoked potentials w4x, fMRI w13x and PET w17x. The neuromagnetic measurements of subject PB, extending over a period of more than 3 months while training almost every day for 3 h to discriminate small differences in frequency and intensity between two tones, revealed a progressive decrease in the amplitude of the waveforms while performance improved. A decrease in amplitude of the evoked magnetic fields found in these experiments, instead of an amplitude enhancement reported for previous studies, can be explained by the fact that none of the previous human studies have reported physiological measurements associated with the same large amount of training hours as employed in this study. The subjects of Karni et al. w13x trained for sequences of finger movements for sessions of 10–20 min during 5 weeks, and the subjects of Ciesielski and French w4x trained in a visual matching task for 2.5 h. The plasticity described in the present study is in accordance with the postulate that the process of learning is associated by a gradual shift from a slow, laborious and controlled process to a fast, effortless and automatic process w4,23x. Behavioral data in subject PB clearly reflect this tendency, with reaction time decreasing and confidence level increasing with training. As for the behavioral data, the macrophysiological recordings obtained magnetically present this same tendency, which is reflected in the ampli-

S. Cansino, S.J. Williamsonr Brain Research 764 (1997) 53–66

tude decrease of the neural responses evoked by the stimuli in the task. This decrement might indicate that the subject is using fewer resources to deal with the task as the training increases and that correct discrimination may require a more discrete cortical activation so inhibitory processes become more forceful with learning. No latency differences were detected in the 100 ms components with learning. No general conclusions can be drawn from only one subject, and the present study was designed to characterize the order of magnitude of the effort required to detect physiological plasticity in human sensory cortical areas associated with learning a discrimination task. The decrease in response amplitude associated with the learning sessions carried out by subject PB is present in both the 100m component of the primary auditory cortex and the L100m component of the association auditory cortex. Vogels and Orban w24x explored whether training for a visual orientation discrimination task changes neural responses of the temporal cortical visual area TE of macaque monkeys. The unit recordings from these cells of their two subjects did not show any neural response differences after training. The decrease in amplitude of the L100m component from the auditory association cortex found in the present study shows that also in late processing areas and not only in early sensory areas it is possible to detect a physiological plasticity. From stage 1 to 2 strong amplitude decrements were observed after only 1800 trials. Subject PB exhibited an amplitude decrement of the 100 ms components between stages 1 and 2 that was stronger in the right hemisphere than the left. What is interesting, and might explain these results, is that Fig. 2 reveals that subject PB needed very few trials at the beginning to improve from the first discrimination level Ž50 Hz and 5 dB. to a more advanced level Ž40 Hz and 3 dB., and this performance improvement is reflected in the physiological recordings. Experiments using learning paradigms have also revealed evoked potential differences between hemispheres as gauged by the latency of the P235 component w10x. In summary, the present study found that neuromagnetic fields exhibit sensitivity to performance and provide evidence of plasticity in primary and association auditory cortices. The following central findings are derived from these experiments: the magnetic field pattern is significantly stronger for incorrect responses compared with correct responses, during the first 70 ms and sometimes also at 100 ms latencies, after the onset of the probe stimulus when subject performance was correct for at least 75% of the trials. There were no differences in strength when performance is not better than chance. Learning to discriminate small differences in frequency and intensity between isolated tones requires a significant amount of time, and this learning process is associated with a change in detectible brain activity. The amplitudes of the 100m component of the primary auditory cortex and the L100m component of the association auditory cortex decrease during the

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process of learn to execute the auditory discrimination task over 74 200 trials. These physiological changes are associated with an improvement in subject’s performance.

Acknowledgements We thank Lloyd Kaufman for motivating this investigation of physiological correlates to learning. James Moeller devised the algorithm for field contrast and kindly provided it for our use. This research was supported in part by a grant from CONACYT, Mexico Ž4511-H., by a grant from DGAPA, National Autonomous University of Mexico ŽIN300495. and by a grant to New York University from the Horace W. Goldsmith Foundation. Our special gratitude goes to subject PB who contributed more than 74 000 responses for this research.

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